Hormone Discovered That Preserves Insulin Production and Beta Cell Function in Diabetes

The new hormone was found to stimulate insulin secretion from rat and human islet cells and protect islet cells in the presence of toxic, cell-killing factors used in the study.

The findings provide insight into the health and survival of beta cells, a type of islet cell that produces insulin to regulate sugar levels. The discovery could open pathways for further research toward prevention and treatments for type 1 diabetes and type 2 diabetes.

The researchers gave the hormone, TLQP-21 to Zucker Diabetic Fatty rats, which have a genetic propensity to develop type 2 diabetes. They saw a significant improvement in insulin and glucose (sugar) levels and less beta cell death in the treated animals.

Senior author Christopher B. Newgard, Ph.D., director of the Sarah W. Stedman Nutrition and Metabolism Center, stated that, "We think this finding is important because it is the first demonstration that TLQP-21 prevents deterioration of the beta cells and stimulates insulin secretion in the presence of glucose." "Because diabetes starts to take hold when the number of beta cells dwindles and insulin production drops, finding the best way to produce more of this protective hormone could be valuable."

Although the researchers have so far only tested TLQP-21 in models of type 2 diabetes, they plan to test the hormone in type 1 in future studies.

TLQP-21 is similar in some of its functions to another naturally occurring hormone produced in the digestive tract, glucagon-like peptide-1 (GLP-1). Through different mechanisms, both hormones protect and promote insulin secretion. GLP-1 or drugs that stabilize it are widely used to treat type 2 diabetes, but with some side effects, including increased heart rate and reduced stomach emptying; the effect on intestinal function has caused some people to stop the therapy.

"What's exciting is that in the animal studies of TLQP-21, we didn't see these side effects," said lead author Samuel B. Stephens, Ph.D., a postdoctoral researcher in the Stedman Center. "The rats had typical appetites and ate normal amounts of food, and didn't show any changes in heart rate or digestion patterns when they were given large doses of the hormone." The next step is to find a small molecule that could stimulate the islet cells to produce more of the TLQP-21 hormone, or to develop more potent or stable versions of injected hormone.

Cell Metabolism, July 3, 2012