Issue 148 Item 10 Beta-Cells Suppress Output of Glucagon From Alpha Cells

While nutrients appear to stimulate glucagon secretion by alpha-cells of the pancreas, output is suppressed by activation of neighboring beta-cells. That, according to a report published in the March 17th online issue of Nature Cell Biology. Many studies have evaluated the mechanisms involved in glucose-mediated insulin secretion from beta-cells, Dr. Claes B. Wollheim and colleagues, from the University Medical Center in Geneva, note. In contrast, relatively little research has focused on the mechanisms of alpha-cell secretion of glucagon, which raises glucose levels. Dr. Wollheim’s team used conventional pancreas perfusion and a transcriptional targeting technique to evaluate signal transduction in alpha-cells and the interaction of alpha- and beta-cells. The researchers found that alpha-cells released glucagon in response to pyruvate, the principle substrate of mitochondria. In a physiologic system, glucagon then worked to increase blood glucose levels, they add. So what is the alpha-cell response to pyruvate if blood glucose levels are already high? In their test system, the authors found that this situation activates beta-cells to release a substance that suppresses glucagon secretion by the alpha-cells, which may serve to prevent a further rise in glucose levels. The glucagon-suppressing factor appeared to be zinc. “Our results define the fundamental mechanism of differential response to identical stimuli between cells in a micro-organ,” the authors note. “Further work is needed to clarify the precise mechanism by which zinc released from beta-cells inhibits glucagon secretion,” they add. Nat Cell Biol 2003. www.nature.com/naturecellbiology. =============================== Having the results of your patients A1c while you are with them can motivate them to better self control. www.a1cnow.net