beta-cell adaptation in 60% pancreatectomy rats that preserves normoinsulinemia and normoglycemia.
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.
Liu
Y Q
YQ
Division of Endocrinology, Diabetes and Metabolism, University of Vermont, Burlington, Vermont 05405, USA.
Nevin
P W
PW
Leahy
J L
JL
D000222:Adaptation, Physiological; D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D005941:Glucokinase / Q000378:metabolism; D015151:Immunoblotting; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000503:physiopathology*; D010180:Pancreatectomy / Q000379:methods*; D011184:Postoperative Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D005941:Glucokinase