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.
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