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-Cell adaptation in 60% pancreatectomy rats that preserves
normoinsulinemia and normoglycemia
Division of Endocrinology, Diabetes and Metabolism, University of Vermont, Burlington, Vermont 05405
Islet
-cells are the regulatory element of the glucose homeostasis system.
When functioning normally, they precisely counterbalance changes in
insulin sensitivity or
-cell mass to preserve normoglycemia. This
understanding seems counter to the dogma that
-cells are regulated
by glycemia. We studied 60% pancreatectomy rats (Px) 4 wk postsurgery
to elucidate the
-cell adaptive mechanisms. Nonfasting glycemia and
insulinemia were identical in Px and sham-operated controls. There was
partial regeneration of the excised
-cells in the Px rats, but it
was limited in scope, with the pancreas
-cell mass reaching 55% of
the shams (40% increase from the time of surgery). More consequential
was a heightened glucose responsiveness of Px islets so that glucose
utilization and insulin secretion per milligram of islet protein were
both 80% augmented at normal levels of glycemia. Investigation of the
biochemical basis showed a doubled glucokinase maximal
velocity in Px islets, with no change in the glucokinase
protein concentration after adjustment for the different
-cell mass
in Px and sham islets. Hexokinase activity measured in islet extracts
was also minimally increased, but the glucose 6-phosphate concentration
and basal glucose usage of Px islets were not different from those in
islets from sham-operated rats. The dominant
-cell adaptive response
in the 60% Px rats was an increased catalytic activity of glucokinase.
The remaining
-cells thus sense, and respond to, perceived
hyperglycemia despite glycemia actually being normal.
-Cell mass and
insulin secretion are both augmented so that whole pancreas insulin
output, and consequently glycemia, are maintained at normal levels.
glucokinase; glucose metabolism; glycolysis; glucose 6-phosphate; islets of Langerhans; insulin secretion
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