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Postprandial Suppression of Glucagon Secretion Depends on Intact Pulsatile Insulin Secretion

Further Evidence for the Intraislet Insulin Hypothesis

  1. Juris J. Meier1,
  2. Lise L. Kjems1,
  3. Johannes D. Veldhuis2,
  4. Pierre Lefèbvre3 and
  5. Peter C. Butler1
  1. 1Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, Los Angeles, California
  2. 2Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota
  3. 3Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, Centre Hospitalier Universitaire du Sart Tilman, Liège, Belgium
  1. Address correspondence and reprint requests to Peter C. Butler, Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, 24-130 Warren Hall, 900 Veteran Ave., Los Angeles, CA 90095-7073. E-mail: pbutler{at}mednet.ucla.edu

Abstract

Type 2 diabetes is characterized by an ∼60% loss of β-cell mass, a marked defect in postprandial insulin secretion, and a failure to suppress postprandial glucagon concentrations. It is possible that postprandial hyperglucagonemia in type 2 diabetes is due to impaired postprandial insulin secretion. To address this, we studied eight adult Goettingen minipigs before and after an ∼60% reduction in β-cell mass induced by alloxan. Pigs were studied fasting and after ingestion of a mixed meal. Insulin and glucagon secretion were determined by deconvolution of blood hormone concentrations measured at 1-min intervals. The relationship between insulin and glucagon release was analyzed using cross-correlation and forward versus reverse cross–approximate entropy. We report that glucagon and insulin were secreted in ∼4-min pulses. Prealloxan, postprandial insulin secretion drove an ∼20% suppression of glucagon concentrations (P < 0.01), through inhibition of glucagon pulse mass. The alloxan-induced ∼60% deficit in β-cell mass lead to an ∼70% deficit in postprandial insulin secretion and loss of the postprandial insulin-driven suppression of glucagon secretion. We conclude that postprandial hyperglucagonemia in type 2 diabetes is likely due to loss of intraislet postprandial suppression of glucagon secretion by insulin.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted January 4, 2006.
    • Received November 4, 2005.
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