Partial Inhibition of Insulin Secretion Results in Glucose Intolerance but Not Hyperglucagonemia

  1. Philip E. Cryer1
  1. 1Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
  2. 2Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri
  1. Corresponding author: Philip E. Cryer, pcryer{at}wustl.edu.

Abstract

OBJECTIVE We tested the hypotheses that in nondiabetic individuals, partial inhibition of insulin secretion with the ATP-sensitive K+ channel agonist (opener) diazoxide, compared with placebo, results in higher plasma glucose and higher plasma glucagon concentrations after a mixed meal and after administration of the sulfonylurea glimepiride.

RESEARCH DESIGN AND METHODS Plasma glucose, insulin, C-peptide, and glucagon concentrations were measured every 30 min from −60 through 180 min with random-sequence, double-blind administration of diazoxide (6.0 mg/kg) or placebo at −30 and 1 min, ingestion of a formula mixed meal (Ensure Plus) at 0 min after diazoxide and after placebo and, on a separate occasion, ingestion of glimepiride (4.0 mg) at 0 min (with glucose infused to prevent hypoglycemia) after diazoxide and after placebo in 11 healthy young adults.

RESULTS With diazoxide administration, insulin (P = 0.0016) and C-peptide (P = 0.0287) concentrations were decreased and glucose concentrations were increased (e.g., 180-min values of 106 ± 4 mg/dL [5.9 ± 0.2 mmol/L] compared with 87 ± 2 mg/dL [4.8 ± 0.1 mmol/L] with placebo; P < 0.0001), but glucagon concentrations were no different after the mixed meal. Similarly, with diazoxide, C-peptide concentrations were decreased (P = 0.0015) and glucose concentrations were increased (P < 0.0001), but glucagon concentrations declined similarly after glimepiride administration.

CONCLUSIONS Partial inhibition of insulin secretion results in impairment of glucose tolerance after a mixed meal and after glimepiride administration in the absence of a difference in glucagon secretion. They underscore the primary glucoregulatory role of insulin and support the evidence that β-cell secretion is not the only regulator of α-cell glucagon secretion.

  • Received November 15, 2010.
  • Accepted February 2, 2011.

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  1. Diabetes vol. 60 no. 4 1324-1328
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