Hyperglycemia alone does not inhibit secretin-induced pancreatic bicarbonate secretion.
Administration of exogenous insulin (INS) inhibits secretin-stimulated pancreatic bicarbonate (HCO3) output via a dose-dependent, neurally mediated mechanism. To determine whether this effect was due to systemic hyperinsulinemia or to reduced endogenous insulin production, we examined the effect of hyperglycemia on secretin-stimulated pancreatic secretion. Chronic pancreatic fistulae were created in six dogs. After 30 minutes of equilibration, a computer-assisted hyperglycemic clamp protocol was used to maintain glucose (GLU) levels 100 or 150 mg/dL above basal in clamp animals; control animals received volume- and rate-matched infusions of 0.9% saline. One hour after beginning the clamp period, intravenous secretin dose-response (16-125 ng/kg/h) was begun, doubling the dose every half hour. Unstimulated (0-30 minutes) HCO3, GLU, and INS levels did not differ between groups. INS and GLU levels in clamp animals were significantly elevated during clamp (30-90 minutes) and stimulated (90-210 minutes) periods. For the same periods, HCO3 secretion was not significantly changed despite profound hyperinsulinemia. We conclude that systemic hyperinsulinemia alone does not inhibit secretin-stimulated HCO3 output. Since exogenous INS exerts feedback regulation on the pancreas, we propose that suppression of endogenous INS secretion mediates the previously reported inhibitory response.
Simon
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T
Atlanta Veteran Affairs Medical Center, and Department of Surgery, Emory University, Georgia 30033, USA.
Marcus
A
A
Royce
C L
CL
Chao
F
F
Mendez
T
T
Fink
A S
AS
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D004285:Dogs; D015309:Glucose Clamp Technique; D006943:Hyperglycemia / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D012633:Secretin / Q000008:administration & dosage / Q000494:pharmacology*
D001639:Bicarbonates; D001786:Blood Glucose; D007328:Insulin; D012633:Secretin