Diabetes currently affects 24 million individuals in the United States alone. The incidence of adult onset or Type II diabetes has increased 15 percent over the last two years, targeting nearly a quarter of individuals over 60. Worldwide, the incidence of diabetes is predicted to double by 2030, accounting for nearly 370 million people. By any measure, this disease has reached epidemic proportions.
Key to the development of either Type 1 or Type II diabetes is the inability of the pancreas to produce enough insulin, either because the number of insulin producing islet cells is too low, or because the target cells become deaf to insulin's message. Salk scientists are working on understanding the molecular and genetic basis of the disease to advance the development of possible future treatments and perhaps a cure.
Salk researchers discovered how a hormone turns on a series of molecular switches inside the pancreas that increases production of insulin.The molecular switches command pancreatic beta islet cells, the cells responsible for insulin, to grow and multiply. Tweaking these cells might offer a solution to type 1 diabetes, the form of diabetes caused by destruction of islet cells, and to type II diabetes, the form caused by insulin resistance.
Researchers have identified a possible link between diabetes and cancer by studying AMPK, a key cellular enzyme involved in conserving energy when glucose levels run low, and its master regulator LKB1, a tumor-suppressing protein. It turns out that the widely used Type II diabetes drug Metformin activates AMPK, suggesting that the LKB1/AMPK pathway is a molecular link between the two diseases. This may explain the increased cancer risk seen in Type II diabetic patients.
Scientists have discovered how two key proteins, CRTC2 and FOXO1, work in concert to fire up the body's mechanism to rapidly produce and maintain the necessary levels of glucose for the brain during times of fasting. Their findings may pave the way for novel therapies for those who suffer from metabolic diseases in which such regulation can spiral out of control.
Using a compound that artificially turned on PPAR delta, a genetic switch that controls the ability for cells to burn fat, scientists tricked muscles in mice into thinking they had been exercised, while also dramatically boosted endurance by more than 70 percent when combined with exercise. This amazing breakthrough may one day provide much-needed relief to those who cannot physically exercise as a result of trauma or disease.
Additional studies have established that the PPAR delta gene also exerts powerful anti-inflammatory effects in arteries suppressing the development of atherosclerosis, while a collaborative effort among scientists at Salk has led to the remarkable discovery that endurance can also be stimulated through the activation of a central switch called AMPK, which then turns on PPAR delta. These findings indicate that single agents are able to reprogram adult muscle towards endurance fibers in a manner previously unimagined.
Ronald M. Evans
Professor and Director
Gene Expression Laboratory
Howard Hughes Medical Institute Investigator March of Dimes Chair in Molecular and Developmental Biology
Marc R. Montminy
Clayton Foundation Laboratories for Peptide Biology
J.W. Kieckhefer Foundation Chair
Reuben J. Shaw
Molecular and Cell Biology Laboratory
Howard Hughes Medical Institute Early Career Scientist
Inder M. Verma
Laboratory of Genetics
American Cancer Society Professor of Molecular Biology Irwin and Joan Jacobs Chair in Exemplary Life Science
Salk study may offer drug-free intervention to prevent obesity and diabetes
May 17, 2012
It turns out that when we eat may be as important as what we eat. Scientists at the Salk Institute for Biological Studies have found that regular eating times and extending the daily fasting period may override the adverse health effects of a high-fat diet and prevent obesity, diabetes and liver disease in mice. Read more>>
Sugar production switch in liver may offer target for new diabetes therapies
April 08, 2012
In their extraordinary quest to decode human metabolism, researchers at the Salk Institute for Biological Studies have discovered a pair of molecules that regulates the liver's production of glucose—the simple sugar that is the source of energy in human cells and the central player in diabetes.
From feast to famine: A metabolic switch that may help diabetes treatment
April 24, 2011
Humans are built to hunger for fat, packing it on during times of feast and burning it during periods of famine. But when deluged by foods rich in fat and sugar, the modern waistline often far exceeds the need to store energy for lean times, and the result has been an epidemic of diabetes, heart disease and other obesity-related problems.
Now, scientists at the Salk Institute for Biological Studies have identified the linchpin of fat metabolism, a protein known as fibroblast growth factor 1 (FGF1), which may open new avenues in the treatment of diabetes.
"Fasting pathway" points the way to new class of diabetes drugs
May 12, 2011
A uniquely collaborative study by researchers at the Salk Institute for Biological Studies uncovered a novel mechanism that turns up glucose production in the liver when blood sugar levels drop, pointing towards a new class of drugs for the treatment of metabolic disease.
Their findings, published in the May 13, 2011, issue of the journal Cell, revealed a crucial role for so called histone deacetylases (HDACs), a group of enzymes that is the target of the latest generation of cancer drugs. HDACs get sugar production rolling when blood glucose levels run low after prolonged periods of fasting or during the night. Read more>>
What Our Genes Tell Us about Obesity and Diabetes
September 13, 2011
According to the latest figures, nearly 25.8 million children and adults in the United States have diabetes, 7 million of those remain undiagnosed and an estimated 79 million people are at risk of developing the condition. It’s the sixth leading cause of death, and it costs our country more than $116 billion annually in direct medical costs. What is more, the Centers for Disease Control estimate that if current trends continue, by 2050, the number of Americans with diabetes will triple, with a staggering 1 in 3 affected.
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