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Am J Physiol Endocrinol Metab 279: E68-E73, 2000;
0193-1849/00 $5.00
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Vol. 279, Issue 1, E68-E73, July 2000

beta -Cell adaptation in 60% pancreatectomy rats that preserves normoinsulinemia and normoglycemia

Ye Qi Liu, Peter W. Nevin, and Jack L. Leahy

Division of Endocrinology, Diabetes and Metabolism, University of Vermont, Burlington, Vermont 05405

Islet beta -cells are the regulatory element of the glucose homeostasis system. When functioning normally, they precisely counterbalance changes in insulin sensitivity or beta -cell mass to preserve normoglycemia. This understanding seems counter to the dogma that beta -cells are regulated by glycemia. We studied 60% pancreatectomy rats (Px) 4 wk postsurgery to elucidate the beta -cell adaptive mechanisms. Nonfasting glycemia and insulinemia were identical in Px and sham-operated controls. There was partial regeneration of the excised beta -cells in the Px rats, but it was limited in scope, with the pancreas beta -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 beta -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 beta -cell adaptive response in the 60% Px rats was an increased catalytic activity of glucokinase. The remaining beta -cells thus sense, and respond to, perceived hyperglycemia despite glycemia actually being normal. beta -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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