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Showing posts with label diabetes. Show all posts
Showing posts with label diabetes. Show all posts

October 10, 2014

Stem-Cell Breakthrough cures diabetic mice in less than 10 days

In what may lead to the biggest breakthrough in the treatment of Type 1 diabetes in three decades, Xander University Professor Douglas Melton and colleagues have figured out the complex series of steps necessary to turn stem cells into beta cells. Beta cells are the sugar-sensing, insulin-secreting cells of the pancreas that are missing in Type 1 diabetics, casualties of the body’s own immune attack on itself.

“We wanted to replace insulin injections” with “nature’s own solution,” says Melton, who has been a leading scientist in and advocate for the field of stem-cell biology ever since he switched from studying developmental biology in frogs after his young son, and later his daughter, were diagnosed with Type 1 diabetes.

They have succeeded in developing a procedure for making hundreds of millions of pancreatic beta cells in vitro. These cells, Melton explains, “read the amount of sugar in the blood, and then secrete just the right amount insulin in a way that is so exquisitely accurate that I don’t believe it will ever be reproduced by people injecting insulin or by a pump injecting that insulin.”

In diabetic mice, they cure diabetes right away, in fewer than 10 days.



Journal Cell - Generation of Functional Human Pancreatic β Cells In Vitro

October 01, 2014

New treatments show promise in prolonging human lifespan, when can you get it?

Evidence is emerging that some widely used drugs can prolong lifespan for well people – and insiders have started taking them off-label.

Millions of people are taking anti-ageing drugs every day – they just don't know it. Drugs to slow ageing sound futuristic but they already exist in the form of relatively cheap medicines that have been used for other purposes for decades.

Google and Venter's plans may have injected an over-hyped field with a measure of credibility but they are unlikely to bear fruit for some time. Yet evidence is emerging that some existing drugs have modest effects on lifespan, giving an extra 10 years or so of life. "We can develop effective combinations for life extension right now using available drugs," says Mikhail Blagosklonny of the Roswell Park Cancer Institute in New York.

One of the most promising groups of drugs is based on a compound called rapamycin. It was first used to suppress the immune system in organ transplant recipients, then later found to extend lifespan in yeast and worms. In 2009, mice were added to the list when the drug was found to lengthen the animals' lives by up to 14 per cent, even though they were started on the drug at 600 days old, the human equivalent of being about 60.

The first evidence has emerged of one such drug having an apparent anti-ageing effect in humans. A drug called everolimus, used to treat certain cancers, partially reversed the immune deterioration that normally occurs with age in a pilot trial in people over 65 years old.

Nextbigfuture has been covering Rapamycin and Metformin for a few years

Nextbigfuture covered research that the diabetes risk from Rapamycin was overblown.

A big drawback to long-term use of rapamycin, however, is the increase in insulin resistance, observed in both humans and laboratory animals. Rapamycin, by contrast, allowed a buildup of fatty acids and eventually an increase in insulin resistance, which in humans can lead to diabetes. However, the drug metformin can address that concern, and is already given to some diabetic patients to increase lipid oxidation. In lab tests, the combined use of rapamycin and metformin prevented the unwanted side effect.

Antiaging Dr. Terry Grossman has recommended the use of Metformin, exercise, aspirin and lowering iron levels in blood.

I have personally tried to ask doctors to allow metformin or rapamycin use but they will not prescribe it for off label purposes. However, some doctors are able to get it prescribed for themselves.

August 23, 2014

Advancing Regenerative Therapies in Musculoskeltal diseases and diabetes panel at the regenerative biotech conference #rejbio

Speakers on a panel are considerong the possibility of applying a drug design similar to ones emerging from the Alzheimers disease and cancer communities. The feasibility of applying such a model will be considered with the biology of the disease, regulatory concerns and pharma needs in mind.

Aubrey de Grey
Christy Carter, University of Florida
Andrew Martello, Spoonful of sugar
Camillo Ricordi, University of Miami

Christy Carter is trying to solve and prevent Sarcopenia (the loss of muscle tissue as we age)
50% of the loss of strength is the loss of muscle and 50% is something else

FDA is having problems allowing for regulation and treatment without clearer definitions of what is going on.

researchers are trying to use behaviorial definitions

Looking at rapamycin for treatment

Dynapenia for muscle weakness

Christy is very hopeful about using SARMS (safe steroids) for fighting sarcopenia.
Myostatin inhibitors have a lot of buzz but the clinical tests are not showing significant sustained strength gains.

Regenerative Medicine Diabetes #rejbio

Breakthroughs in diabetes research is being presented.

The cellular and biological causes of diabetes.

Camillo Ricordi - Cellular therapies and regenerative medicine strategies for treatment of diabetes

Lipogems in chondropathy (coldplay)

Cell Transplant - A new nonenzymatic method and device to obtain a fat tissue derivative highly enriched in pericyte-like elements by mild mechanical forces from human lipoaspirates.

Adipose tissue contains multipotent elements with phenotypic and gene expression profiles similar to human mesenchymal stem cells (hMSCs) and pericytes. The chance of clinical translation of the multilineage potential of these cells is delayed by the poor/negligible cell survival within cryopreserved lipoaspirates, the difficulty of ex vivo expansion, and the complexity of current Good Manufacturing Practice (cGMP) requirements for expanded cells. Hence, availability of a minimally manipulated, autologous, hMSC/pericyte-enriched fat product would have remarkable biomedical and clinical relevance. Here, we present an innovative system, named Lipogems, providing a nonexpanded, ready-to-use fat product. The system uses mild mechanical forces in a completely closed system, avoiding enzymes, additives, and other manipulations. Differently from unprocessed lipoaspirate, the nonexpanded Lipogems product encompasses a remarkably preserved vascular stroma with slit-like capillaries wedged between adipocytes and stromal stalks containing vascular channels with evident lumina. Immunohistochemistry revealed that Lipogems stromal vascular tissue included abundant cells with pericyte/hMSC identity. Flow cytometry analysis of nonexpanded, collagenase-treated Lipogems product showed that it was comprised with a significantly higher percentage of mature pericytes and hMSCs, and lower amount of hematopoietic elements, than enzymatically digested lipoaspirates. Differently from the lipoaspirate, the distinctive traits of freshly isolated Lipogems product were not altered by cryopreservation. Noteworthy, the features of fresh product were retained in the Lipogems product obtained from human cadavers, paving the way to an off-the-shelf strategy for reconstructive procedures and regenerative medicine. When placed in tissue culture medium, the Lipogems product yielded a highly homogeneous adipose tissue-derived hMSC population, exhibiting features of hMSCs isolated from other sources, including the classical commitment to osteogenic, chondrogenic, and adipogenic lineages. Moreover, the transcription of vasculogenic genes in Lipogems-derived adipose tissue hMSCs was enhanced at a significantly greater extent by a mixture of natural provasculogenic molecules, when compared to hMSCs isolated from enzymatically digested lipoaspirates.

David Schaffer. Molecular elucidation and engineering of stem cell therapies for the nervous system

June 19, 2014

Wireless glucose monitoring via and iphone app that is automatically updated every 5 minutes

A bionic pancreas has been developed and it offers hope of a normal life to people with type 1 diabetes.

The device takes over the task of monitoring and regulating sugar levels in the blood. Every 5 minutes, a signal is sent wirelessly from a glucose monitor under the user's skin to an iPhone app, giving their blood-sugar status. The app calculates the amount of insulin or glucagon needed to balance blood sugar, sending a signal to pumps carried by the user to administer the required dose via a catheter. Before eating, people can input data about the type and size of their meal.

The artificial pancreas performed well in hospital-based clinical trials in 2010. But the important test is whether it works in a real-world environment. In the latest study, 20 adults wearing the device were put up in a hotel for five days but were otherwise free to do as they chose, including eat in restaurants and go to the gym. Thirty-two young people, aged 12 to 20, were also monitored for five days at a summer camp for kids with diabetes. For both groups, the results with the bionic pancreas were compared with five days of the participants using their usual method of controlling the disease – pricking their finger to monitor glucose levels and using an insulin pump, that requires them to manually calculate the dosage.

"The device performed beyond our expectations, it did a wonderful job of controlling their blood sugar," says Damiano. Both the highs and lows of sugar levels were better controlled than what the participants were able to do managing their own diabetes prior to the trial, he says.

That is important because as many studies have shown, the better you control your glucose, the closer it is to normal range, the longer you can stave off the long-term health complications of diabetes, says Damiano.


Panel A shows the superimposition of tracings of mean glucose levels on continuous monitoring at all 5-minute steps during the 5-day period in all 20 patients in the adult study during the period when they were wearing the bionic pancreas (black) and during the control period (red). Each tracing is surrounded by an envelope (of corresponding color) that spans 1 SD in either direction around the mean glucose level at each 5-minute step. The mean glucose level during the bionic-pancreas period was 137 mg per deciliter, as compared with 158 mg per deciliter during the control period. Panel B shows tracings for the 32 patients in the adolescent study. The mean glucose level during the bionic-pancreas period was 147 mg per deciliter, as compared with 158 mg per deciliter during the control period. The shaded areas at the bottom of the two panels show clinically significant levels of glucose, including less than 50 mg per deciliter, indicating hypoglycemia (pink); 70 to 120 mg per deciliter, indicating good control (green); and 121 to 180 mg per deciliter, indicating mild hyperglycemia (blue between white lines). To convert the values for glucose to millimoles per liter, multiply by 0.05551.

New England Journal of Medicine - Outpatient Glycemic Control with a Bionic Pancreas in Type 1 Diabetes

March 19, 2014

Microbes and Metabolites sequenced for Venter's Anti-aging company Human Longevity

Craig Venter’s new company wants to improve human longevity by creating the world’s largest, most comprehensive database of genetic and physiological information.

Human Longevity Inc. (HLI) is a genomics and cell therapy-based diagnostic and therapeutic company. HLI will use advances in genomic sequencing, understanding the human microbiome, proteomics, informatics, computing, and cell therapy technologies to make progress to radical life extension. HLI is concentrating on cancer, diabetes and obesity, heart and liver diseases, and dementia.

Human Longevity, based in San Diego, says it will sequence some 40,000 human genomes per year to start, using Illumina’s new high-throughput sequencing machines at a cost of about $1000 per genome.

Eventually, it plans to work its way up to 100,000 genomes per year. The company will also sequence the genomes of the body’s multitudes of microbial inhabitants, called the microbiome, and analyze the thousands of metabolites that can be found in blood and other patient samples.

By combining these disparate types of data, the new company hopes to make inroads into the enigmatic process of aging and the many diseases, including cancer and heart disease, that are strongly associated with it. “Aging is exerting a force on humans that is exposing us to diseases, and the diseases are idiosyncratic, partly based on genetics, partly on environment,” says Leonard Guarente, who researches aging at MIT and is not involved in the company. “The hope for many of us who study aging is that by having interventions that hit key pathways in aging, we can affect disease.”

Human Microbiome - There are 100 times more cells from bacteria, fungi, and viruses, in and on your body than there are human cells. The metabolome includes the complete set of metabolites in a human genome.

April 03, 2012

Metformin Protects against Liver, Oral, Prostate and Pancreatic Cancers

Previously, we had covered Metformin as one of five recommendations for longevity by Dr. Terry Grossman.

Generic metformin costs about 14 cents per 500mg pill.
It has potential side effects of diarrhea and stomach upset.
Need ease onto it. One quarter dose, then half dose then full dose of 2 pills 250-500mg per day.
Need a doctors prescription. If you FBS (fasting blood sugar) 86 or more then consider it and definitely with FBS 100 or more

The recommendations were

Carb Concentration diet (only carbs at one meal per day) - Free
Metformin 14 cents per day
Exercise - Free
Baby aspirin cents per day
Donate blood (to lower iron in the blood) - Free

Other presenters at the personal life extension conference mentioned metformin

Metformin has some MTOR activation (same pathway as Rapamycin)
It extends maximum lifespan of mice by 10%
Useful in humans (seems to be yes).


1. WebMD - The diabetes drug metformin -- commonly a first choice for controlling blood sugar in people with type 2 diabetes -- is sparking new interest as a cancer fighter.

A new study presented here at the American Association for Cancer Research (AACR) annual meeting shows that metformin (Fortamet, Glucophage, Glumetza, Riomet) may put the brakes on the growth of tumor cells in men with prostate cancer. Another study released in one of the association's journals suggests that it may extend the lives of people with pancreatic cancer.

But experts caution that the work is still preliminary and more study is needed before metformin can be recommended as a cancer treatment.

One new study involved 22 men with prostate cancer. They took metformin pills three times a day from the time they got their diagnosis to when they had their prostates removed, an average period of 41 days.

Researchers compared tissue from biopsies taken at diagnosis to tissue removed at the time of surgery and found that metformin slowed the growth of tumor cells by 32%.

Levels of insulin-like proteins in the blood also dropped.

A growing body of evidence -- from lab, animal, and human studies -- suggests metformin mounts a multi-pronged attack against cancer, he tells WebMD. It lowers levels of insulin in the blood, and insulin contributes to the growth of cancer cells

2. Patients with diabetes and pancreatic cancer who are prescribed metformin may have improved survival compared with those not prescribed the commonly used diabetic agent, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.

December 20, 2011

Nerve growth factor gene therapy could prevent diabetic heart disease

New research has investigated if nerve growth factor (NGF) gene therapy can prevent diabetic heart failure and small vascular disease in mice.

The team investigated whether increasing the myocardial level of NGF by using adeno-associated viral (AAV) vectors could prevent the diabetic heart from failure. AAVs are small non-enveloped, single-stranded DNA viruses that can potentially infect all cell types. They exist in different forms, allowing to better target different cells for gene therapy, including after AAV injection in a vein. Importantly, at variance from more popular viral vectors, AAVs allow for virtually permanent increased level of a therapeutic protein.

Professor Emanueli said: “Our study represents a major advance in tackling heart disease in diabetics, a leading cause of death in the western world. It also represents one important step forward in our goal for translating NGF-based therapies in cardiovascular patients.

25.8 million children and adults in the United States—8.3% of the population—have diabetes.

* 79 million people are pre-diabetic.

* 1.9 million new cases of diabetes are diagnosed in people aged 20 years and older in 2010.

* In 2004, heart disease was noted on 68% of diabetes-related death certificates among people aged 65 years or older.

* In 2004, stroke was noted on 16% of diabetes-related death certificates among people aged 65 years or older.

* Adults with diabetes have heart disease death rates about 2 to 4 times higher than adults without diabetes.

In 2007, diabetes was listed as the underlying cause on 71,382 death certificates and was listed as a contributing factor on an additional 160,022 death certificates. This means that diabetes contributed to a total of 231,404 deaths.

June 06, 2011

Gene therapy reverses type 1 diabetes in mice with 78% success rate

An experimental cure for Type 1 diabetes has a nearly 80 percent success rate in curing diabetic mice. The results, to be presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston, offer possible hope of curing a disease that affects 3 million Americans.

"With just one injection of this gene therapy, the mice remain diabetes-free long term and have a return of normal insulin levels in the body," said Vijay Yechoor, MD, the principal investigator and an assistant professor at Baylor College of Medicine in Houston.

March 30, 2011

Pathfinder Cells Demonstrate Ability to Regenerate Damaged Tissue and Restore Pancreatic Function in a Diabetic Mouse Model

A unique cell-based therapy is able to completely reverse diabetes in a mouse model.

"Though preliminary, the robustness of these results is very encouraging," stated Paul G. Shiels, Ph.D., University of Glasgow, Glasgow, United Kingdom. "With only two treatments with PCs, just days after induction of diabetes, we were able to quickly regenerate critically damaged pancreatic tissue, restoring and maintaining normal glucose levels and healthy body weight. Importantly, these results enhance our understanding of the mechanisms of self-repair, elicited by PCs, which may represent a novel cell therapy-based approach to treating diseases marked by tissue damage and loss of organ function."

September 15, 2010

CD8+ regulatory T Cells prevent the immune system from attacking its own cells in mice

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Dana-Farber Cancer Institute scientists to identify cells (CF8+ T regulatory cells) in mice that prevent the immune system from attacking the animals' own cells, protecting them from autoimmune diseases such as multiple sclerosis, type 1 diabetes, and lupus. The significance of this work is that CD8+ Treg cells represent a new lever for raising or lowering the strength of the immune response.

September 10, 2010

University of Kansas researchers show drug can stop debilitating condition of diabetes in mice

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University of Kansas researchers recently published an article showing that KU-32 can stop and even reverse diabetic peripheral neuropathy, or DPN, in mice. The condition leads to death of nerves in the extremities of individuals with diabetes. The drug is still in pre-clinical development. It will likely need another year or two of study, then the researchers hope it could be advanced to clinical trials in humans.

“People with DPN can be very sensitive to light touch, which can cause significant pain,” said Rick Dobrowsky, professor of pharmacology and toxicology and one of the paper’s authors. “The other side is eventually diabetes causes death of the nerves. DPN often leads to loss of feeling in the hands and feet, which can make diabetics susceptible to wounds and infections and often leads to amputations of toes and feet.” DPN is the second leading cause of amputations, after injuries.


ASN Neuro - Inhibiting heat-shock 90 protein 90 reverses sensory hypoalgesia in diabetic mice

September 02, 2010

UCSF unveils model for implantable artificial kidney to replace dialysis

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A model of the implantable bioartificial kidney shows the two-stage system. Thousands of nanoscale filters remove toxins from the blood, while a BioCartridge of renal tubule cells mimics the metabolic and water-balance roles of the human kidney.
UCSF researchers today unveiled a prototype model of the first implantable artificial kidney, in a development that one day could eliminate the need for dialysis. The device, which would include thousands of microscopic filters as well as a bioreactor to mimic the metabolic and water-balancing roles of a real kidney, is being developed in a collaborative effort by engineers, biologists and physicians nationwide, led by Shuvo Roy, PhD, in the UCSF Department of Bioengineering and Therapeutic Sciences.

The team has established the feasibility of an implantable model in animal models and plans to be ready for clinical trials in five to seven years.

End-stage renal disease, or chronic kidney failure, affects more than 500,000 people per year in the United States alone, and currently is only fully treated with a kidney transplant. That number has been rising between 5-7 percent per year, Roy said, in part because of the kidney damage associated with diabetes and hypertension.

Yet transplants are difficult to obtain: a mere 17,000 donated kidneys were available for transplant last year, while the number of patients on the transplant waiting list currently exceeds 85,000, according to the Organ Procurement ant Transplant Network.

Roughly 350,000 patients are reliant on kidney dialysis, Roy explained, which comes at a tremendous cost. The Medicare system alone spends $25 billion on treatments for kidney failure – more than 6 percent of the total budget – while the disease affects only 1 percent of Medicare recipients

June 02, 2010

Various Insulin Pills in Clinical Trials and Targeted Nanosponge Drug Delivery is Three to Five times more Effective against Cancer Tumors

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1. There are various clinical trials for insulin pills. Being able to deliver proteins in time released pill form could provide many benefits for insulin and other conditions.

The human body is designed to digest proteins. Acids and enzymes in the gastrointestinal tract will chew up a valuable therapeutic protein as easily as they’ll tear into a bite of steak. To avoid this fate and reach the intended target, most protein pharmaceuticals are formulated for injection or intravenous infusion. As a result, large amounts of drug tend to be administered less often.

The global diabetes market exceeds $30 billion annually, with insulin sales accounting for about half of that, according to the market research firm IMS Health. If new solid doses can perform at least as well as, if not better than, existing products, they might promise new sales, lower costs of delivery, and extended patent life. Fortunately for drug developers, recombinant production can make enough insulin inexpensively for the larger doses required in oral forms.

April 08, 2010

University of Calgary Researchers Use Nanoparticle "Vaccine" to Cure Type 1 Diabetes in Mice

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Using an innovative nanotechnology-based "vaccine," researchers were able to successfully restore normal blood sugar in mice with type 1 diabetes, and also slow the onset of diabetes in mice at risk for the disease. The study, co-funded by JDRF and published today in the online edition of the journal Immunity, has several key implications:

* First, it provides important new insights into how to stop the immune attack that causes type 1 diabetes.

* Second, it underscores the potential of "antigen-specific" therapies. Because the nanoparticle vaccine was designed with specific immune system proteins, it effectively blunted the targeted autoimmune response that causes diabetes without compromising the overall immune system - an issue that continues to be a challenge in developing treatments for diabetes.

* And third, it suggests that antigen-specific nanovaccines, because of the effectiveness shown here, might also be developed to treat other autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis. That could make the science more attractive to drug development companies.

February 08, 2010

Research Advances Potential For Regeneration As A Possible Cure For Type 1 Diabetes

A hormone responsible for the body's stress response is also linked to the growth of insulin-producing cells in the pancreas, according to JDRF- funded researchers at the Salk Institute for Biological Studies in California. The findings are the latest advances to underscore the potential for regeneration as a key component of a possible cure for type 1 diabetes.

"Being able to stimulate beta cells to divide a little faster may be part of a solution that may ultimately, hopefully, allow management of type 1 diabetes," Dr. Vale says. "But because it is an autoimmune condition, making the cells divide won't be enough. That is why researchers are working hard to solve the problem of destruction of beta cells."



The study showed that the stress hormone could increase the rate at which insulin-producing cells in the pancreas expand in animal models.

In addition to regenerating or replacing insulin producing cells, a cure for type 1 diabetes will also involve stopping the autoimmune attack that causes diabetes, and reestablishing excellent glucose control. (There was separate recent progress in making an articifial pancreas that provided better glucose control)

RELATED READING
The current state of home use blogg glucose meters. Cost-effective home diagnostics has become an attractive solution. Blood glucose meters (or BGMs) can now be found in pharmacies everywhere.

The number of people who suffer from diabetes is growing. The CDC (Centers or Disease Control and Prevention) states that 23.6 million Americans had diabetes in 2007, with more cases every year.





February 05, 2010

Breakthrough in Creating First Generation Artificial Pancreas

Using sophisticated computer software, researchers were able to coordinate the actions of a commercially available continuous glucose monitoring device and insulin pump to allow automatic insulin delivery in response to real-time glucose readings.

While using the artificial pancreas system, the children maintained blood sugar levels in the normal range 60% of the time, compared with 40% of the time while using a conventional insulin pump. Between 50% and 70% of hypoglycemic emergencies happen at night.

If that goes well, he says the artificial pancreas could be clinically available within three to five years for overnight use.

It will probably take longer to determine if the system can be used 24 hours a day. Daytime blood sugar control, especially around mealtimes, poses a special challenge



The system proved better than a conventional insulin pump for maintaining optimal blood sugar levels during the night in a study from the U.K.'s University of Cambridge.

The newly published study included 19 children and teens with type 1 diabetes who used the artificial pancreas system for 33 nights and a conventional insulin pump for 21 nights in a hospital setting.

During certain nights, the delivery systems were challenged by having the children eat a large meal or exercise before bedtime. Both of these activities increase the risk for nighttime hypoglycemia.

While using the artificial pancreas system, the children maintained blood sugar levels in the normal range 60% of the time, compared with 40% of the time while using a conventional insulin pump. Between 50% and 70% of hypoglycemic emergencies happen at night.





January 05, 2010

Leptin-controlled gene can reverse diabetes

Researchers developed a set of conditions in which leptin treatment potently improves diabetes independent of its ability to correct weight and food intake. The new findings confirm what some at least had already suspected: that leptin's antidiabetic effects are independent of the hormone's well-known ability to reduce body weight. Researchers have found that even a very little bit of the fat hormone leptin goes a long way when it comes to correcting diabetes. The hormone controls the activity of a gene known as IGFBP2 in the liver, which has antidiabetic effects in animals and could have similar therapeutic effect in humans. "It was surprising to me how potent leptin was in treating diabetes," said Jeffrey Friedman of Rockefeller University. "It had a highly significant impact at plasma levels that were undetectable."

Cell Metabolism journal - Antidiabetic Effects of IGFBP2, a Leptin-Regulated Gene

We tested whether leptin can ameliorate diabetes independent of weight loss by defining the lowest dose at which leptin treatment of ob/ob mice reduces plasma glucose and insulin concentration. We found that a leptin dose of 12.5 ng/hr significantly lowers blood glucose and that 25 ng/hr of leptin normalizes plasma glucose and insulin without significantly reducing body weight, establishing that leptin exerts its most potent effects on glucose metabolism. To find possible mediators of this effect, we profiled liver mRNA using microarrays and identified IGF Binding Protein 2 (IGFBP2) as being regulated by leptin with a similarly high potency. Overexpression of IGFBP2 by an adenovirus reversed diabetes in insulin-resistant ob/ob, Ay/a, and diet-induced obese mice, as well as insulin-deficient streptozotocin-treated mice. Hyperinsulinemic clamp studies showed a 3-fold improvement in hepatic insulin sensitivity following IGFBP2 treatment of ob/ob mice. These results show that IGFBP2 can regulate glucose metabolism, a finding with potential implications for the pathogenesis and treatment of diabetes
.








Full article available for purchase at Science Direct

August 25, 2009

Genetically engineered gut bacteria trigger intestinal cells to make insulin in mice

MIT Technology Review reports that friendly gut microbes that have been engineered to make a specific protein can help regulate blood sugar in diabetic mice, according to preliminary research presented this week at the American Chemical Society conference in Washington, D.C.
While the research is still in the very early stages, the microbes, which could be grown in yogurt, might one day provide an alternative treatment for people with diabetes.

People with type 1 diabetes lack the ability to make insulin, a hormone that triggers muscle and liver cells to take up glucose and store it for energy. John March, a biochemical engineer at Cornell University, in Ithaca, NY, and his collaborators decided to re-create this essential circuit using the existing signaling system between the epithelial cells lining the intestine and the millions of healthy bacteria that normally reside in the gut. These epithelial cells absorb nutrients from food, protect tissue from harmful bacteria, and listen for molecular signals from helpful bacteria. "If they are already signaling to one another, why not signal something we want?" asks March.

The researchers created a strain of nonpathogenic E. coli bacteria that produce a protein called GLP-1. In healthy people, this protein triggers cells in the pancreas to make insulin. Last year, March and his collaborators showed that engineered bacterial cells secreting the protein could trigger human intestinal cells in a dish to produce insulin in response to glucose. (It's not yet clear why the protein has this effect.)

In the new research, researchers fed the bacteria to diabetic mice. "After 80 days, the mice [went] from being diabetic to having normal glucose blood levels," says March. Diabetic mice that were not fed the engineered bacteria still had high blood sugar levels. "The promise, in short, is that a diabetic could eat yogurt or drink a smoothie as glucose-responsive insulin therapy rather than relying on insulin injections," says Kristala Jones Prather, a biochemical engineer at MIT, who was not involved in the research.




Creating bacteria that produce the protein has a number of advantages over using the protein itself as the treatment. "The bacteria can secrete just the right amount of the protein in response to conditions in the host," says March. That could ultimately "minimize the need for self-monitoring and allow the patient's own cells (or the cells of the commensal E. coli) to provide the appropriate amount of insulin when needed," says Cynthia Collins, a bioengineer at Rensselaer Polytechnic Institute, in Troy, NY, who was not involved in the research.

In addition, producing the protein where it's needed overcomes some of the problems with protein-based drugs, which can be expensive to make and often degrade during digestion. "Purifying the protein and then getting past the gut is very expensive," says March. "Probiotics are cheap--less than a dollar per dose." In underprivileged settings, they could be cultured in yogurt and distributed around a village.

The researchers haven't yet studied the animals' guts, so they don't know exactly how or where the diabetic mice are producing insulin. It's also not yet clear if the treatment, which is presumably triggering intestinal cells to produce insulin, has any harmful effects, such as an overproduction of the hormone or perhaps an inhibition of the normal function of the epithelial cells. "The mice seem to have normal blood glucose levels at this point, and their weight is normal," says March. "If they stopped eating, we would be concerned."

March's microbes are one of a number of new strains being developed to treat disease, including bacteria designed to fight cavities, produce vitamins and treat lactose intolerance. March's group is also engineering a strain of E. coli designed to prevent cholera. Cholera prevention "needs to be something cheap and easy and readily passed from village to village, so why not use something that can be mixed in with food and grown for free?" says March.


August 07, 2009

Some of the Healthcare Discussion Includes Fixing Aging and Disease

Wired Magazine has an article "To Pay for Health Care, Treat Aging"

As politicians try to reform a health care system that could swallow one-fifth of the nation’s economic output by 2020, they should consider making a small bet with a potentially huge payoff: research that could slow the process of aging

In papers published in The Scientist and British Medical Journal, Olshanksy and International Longevity Center president Robert Butler wrote that drugs that delay aging’s onset by seven years are now a realistic possibility.

They’re currently in the process of calculating this longevity dividend’s economic benefits. Even if the figures aren’t finalized, however, they’re likely to be massive. For Alzheimer’s disease alone, they estimate that the cost of care will rise to $1 trillion by 2050. The Robert Wood Johnson foundation estimates two-thirds of rising health costs come from chronic diseases

The NIH channels almost all U.S. governmental support for age-delaying research through the National Institute on Aging, but its $1 billion budget is a pittance by federal standards. Nearly $5 billion is earmarked for the National Cancer Institute, and that’s just one disease of aging. Of the NIA’s $1 billion, just $180 million is set aside for research on the biology of aging. That figure has barely changed since 2006.

President Obama’s stimulus package did allot $273 million for the National Institute on Aging, but only a small fraction will likely go to potentially age-delaying research, said Peter Rabinovitch, a University of Washington gerontologist. By contrast, the stimulus plan contains $37 billion for electronic health records.


Recent results indicate that an approved diabetes drug, metformin, may battle aging. Approved in 1995, metformin was marketed as Glucophage.

The UK Prospective Diabetes Study 34 showed that in patients with type II diabetes, metformin treatment resulted in reductions in end-organ damage, myocardial infarction, and all-cause mortality. Stephen Spindler, professor of biochemistry at the University of California, San Diego, has shown that metformin out-performs short-term calorie restriction in inducing the geneexpression changes associated with long-term calorie restriction. Not everyone is persuaded by the metformin results, however. Side effects, such as a small risk of lactic acidosis that can be fatal in certain patients, are not likely worth the risk of lifelong treatment for aging.


Fighting Aging talks about body wide fixes for mitochondria.

We could sidestep all of these issues with a technology that repairs or replaces mitochondrial DNA globally throughout the body - such as protofection, demonstrated back in 2005. If we replace all mitochondrial DNA with fresh new mitochondrial DNA, then it doesn't matter why or how its prior state was causing issues because we just fixed the problem.

This is as good an example as any to show that we don't need complete understanding of human biochemistry in order to make important inroads into repairing the damage of aging. More understanding helps, but we have enough knowledge now to move ahead with significant and important rejuvenation technologies - were there a large research community and the will and funding to forge ahead


From Rafal Smigrodzki - via the Extropy chat list in 2005

Our team confirmed our previous preliminary data showing that we can achieve robust mitochondrial transfection and protein expression in mitochondria of live rats, after an injection of genetically engineered mitochondrial DNA complexed with our protofection transfection agent. A significant fraction of cells in the brain is transfected with this single injection even though we so far did not optimize the dose.

This achievement has important implications for medicine: protofection technology works in vivo, and should be capable of replacing damaged mitochondrial genomes





In Popular Mechanics, Dean Kamen one of the world's most prolific inventors of healthcare technologies, challenges the notion that the U.S. has a healthcare crisis. Rather than slowing the pace of medical progress in order to cut healthcare costs, he argues, America should be encouraging more innovation in life-saving drugs and technologies.

Every drug that's made is a gift from one generation to the next because, while it may be expensive now, it goes off patent and your kids will have it essentially for free. You can't look at the problem and say, "I want them to do more, better, faster miracles—and not invest in research, not invest in development, and have those miracles delivered to me free." It's unrealistic. And people know that about most things. They do. Nobody expects that just because they've made computers better they're going to give them to you free.

We spent on all pharmaceuticals in the United States last year $260 billion. That means all those vaccinations to prevent diseases, all those pills to treat diseases, all those pills to cure them so we don't have to treat them anymore. We spent in all branches of all our pharmaceutical suppliers, $260 billion.

That's certainly way up from what it was in the early days of the world, but we also spent way more money on computers and other things that didn't exist back then, either, and we don't claim we have a computer crisis. We spent more money on our iPhones last year than we did ten years ago cause there were no iPhones. But let me compare $260 billion to other things. How much did we spend in the United States last year on tobacco? $88 billion. That's a significant piece of 260. It's the reason we spent some of that 260. How much did we spend last year on alcohol? The government doesn't subsidize that, you don't have a right to it, it's discretionary spending and if you were really in trouble you would probably spend a little less on alcohol. We spent $90 billion.

Last year what did we spend in the United States on soft drinks? $121 billion. Nearly half of what we spend on all of our pharmaceuticals, on soft drinks. I'm not against soft drinks—I think you ought to buy all the soft drinks you want.

Last year what did we spend supporting professional sports? $409 billion.

Now if somebody in this country wants to explain to me that we ought to be spending about twice as much supporting sports as on all of our pharmaceuticals, then stop spending. You don't like that drug? You don't want to cure this disease? Don't buy it. But don't make villains out of people so that we can turn what is a real social responsibility issue into a political debate.

Diabetes alone, if you include all of the long-term, insidious consequences of a lifetime of diabetes, is responsible for about 30 percent of the federal reimbursement for healthcare. Well, it would kill us if we look at the 30-year actuarial data based on our 19th century confidence in technology. But I'm sure in 1920 if you asked actuaries to say what percentage of our GDP are we going to spend taking care of people with polio, they'd say: "They get polio, it goes to their lungs, they sit in iron lung machines, they could live a whole lifetime with three people watching over them. We can't support them all."

But what did it cost to deal with everybody with polio? Oh, $2 apiece. We gave them the Salk vaccine. But in the 1920s Salk wasn't around yet.


Cures and treatments are not equal. Iron lung style are expensive and bad while vaccines and new treatments like stem cells and gene therapy could be very good.