The Inhibitory Effects of Insulin on Hepatic Glucose Production Are Both Direct and Indirect

  1. Jean Girard
  1. From the Département Endocrinologie, Métabolisme, and Cancer, Institut Cochin, Paris, France; the Institut National de la Santé et de la Recherche Médicale, Paris, France; the Centre National de la Recherche Scientifique, Paris, France; and the Faculté de Médecine René Descartes, Université Paris, Paris, France
  1. Address correspondence and reprint requests to Jean Girard, Département Endocrinologie, Métabolisme, and Cancer, Institut Cochin, 24 rue du Fbg Saint-Jacques, F-75014 Paris, France. E-mail: girard{at}cochin.inserm.fr

Abstract

Previous studies suggest that insulin can inhibit hepatic glucose production by both direct and indirect actions. The indirect effects include inhibition of glucagon secretion, reduction in plasma nonesterified fatty acid levels, reduction of the amount of gluconeogenic precursor supplied to the liver, and change in neural input to the liver. There is a controversy concerning the fact that the dominant action of insulin on hepatic glucose production is direct, as suggested by studies in fed dogs, or indirect, via the hypothalamus, as suggested by studies in rodents. A possible explanation for this discrepancy will be proposed involving the relative importance of glycogenolysis and gluconeogenesis in hepatic glucose production in dogs and rodents. Finally, the relative importance of direct and/or indirect effects of insulin on hepatic glucose production for the treatment of diabetes will be discussed.

Footnotes

  • This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Servier.

    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 May 12, 2006.
    • Received March 27, 2006.
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This Article

  1. doi: 10.2337/db06-S009 Diabetes vol. 55 no. Supplement 2 S65-S69