U-M researchers shed new light on glucose metabolism with possible relevance to type 2 diabetes

Les Satin, Ph.D.

Following a meal, the hormone insulin is released into the blood from the pancreas in regularly occurring pulses. These insulin pulses promote nutrient storage and help to restore blood sugar to normal levels. The pulses of insulin work more effectively than a constant level of insulin, and in Type 2 diabetic patients, they disappear. An important question, then, is where do the insulin pulses come from?

New research from the University of Michigan Health System that appears in the Journal of Biological Chemistry helps answer that question.

Les Satin, Ph.D., a professor in the Department of Pharmacology at the U-M Medical School and the Brehm Diabetes Research Center has been searching for the origin of insulin oscillations by studying the cells that produce and release insulin, pancreatic beta-cells. An important clue came from studies of yeast, which contain a glycolytic enzyme called phosphofructokinase that produces oscillations in fructose 1,6-bisphosphate.

Researchers in the Satin lab suspected that phosphofructokinase, which is also found in pancreatic beta-cells, could produce oscillations in metabolism capable of stimulating pulses of insulin release. In fact, this is the case.

Matthew Merrins, Ph.D.

Matthew Merrins, Ph.D., a postdoctoral fellow in the lab, constructed a new protein sensor called PKAR, to detect levels of fructose 1,6-bisphosphate in the cell. When the Satin research team introduced PKAR sensors into yeast, or pancreatic beta-cells, they saw oscillations of metabolism when sugar was present. The pulses had the right timing to explain the insulin pulses seen in the bloodstream of mice, rats, and humans.

Their work suggests that glycolytic oscillations are evolutionarily conserved from yeast to mammals. With their new sensor, Satin’s group can now test whether the loss of insulin pulses in diabetic patients results from the loss of pancreatic glycolytic pulses. If this is the case, the group hopes to provide a way to restore normal insulin pulse patterns in patients to help relieve diabetes.

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