BOSTON July 23, 2012 Scientists at Joslin Diabetes Center have identified biological mechanisms by which glucagon-like peptide-1 (GLP-1), a gut hormone, protects against kidney disease, and also mechanisms that inhibit its actions in diabetes. The findings, which are reported today online by Diabetes, may lead to the development of new therapeutic agents that harness the actions of GLP-1 to prevent the harmful effects of hyperglycemia on renal endothelial cells.
Renal complications, also known as diabetic nephropathy, are one of the most life-threatening complications of diabetes that often lead over time to end-stage renal disease (ESRD). About a half million people in the US 44 percent of whom are diabetics -- have ESRD, which requires dialysis or kidney transplantation. As a result, investigating the relationship of diabetes to renal dysfunction is a major focus of diabetes research. "We are very eager to develop new treatments for diabetic kidney disease," says George King, M.D., lead author of the study, and chief scientific officer, head of the Dianne Nunnally Hoppes Laboratory for Diabetes Complications and a professor of medicine at Harvard Medical School.
GLP-1 is an incretin hormone that is produced by the intestine in response to food. GLP-1 increases the secretion of insulin from the pancreas, slows absorption of glucose from the gut, and reduces the action of glucagon all of which lower glucose levels in the blood. In addition, GLP-1 reduces appetite. The drug, exendin-4 (marketed as Exenatide), which mimics the effects of GLP-1, is used to lower blood glucose in type 2 diabetes.
Recent studies have reported that GLP-1 improves the function of renal endothelial cells (which regulate blood clotting, immune response and blood vessel activity, among other critical functions, and are impaired by insulin resistance) and can prevent some renal pathologies in diabetic rodents. GLP-1 receptors (GLP-1R), which are abund
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Joslin Diabetes Center