Mechanisms of impaired fasting glucose and glucose intolerance induced by a ∼50% pancreatectomy

Aleksey V. Matveyenko, Johannes D. Veldhuis, Peter C. Butler

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) often coexist and as such represent a potent risk factor for subsequent development of type 2 diabetes. β-Cell mass is ∼50% deficient in IFG and ∼65% deficient in type 2 diabetes. To establish the effect of a ∼50% deficit in β-cell mass on carbohydrate metabolism, we performed a ∼50% partial pancreatectomy versus sham surgery in 14 dogs. Insulin secretion was quantified from insulin concentrations measured in the portal vein at 1-min sampling intervals under basal conditions, after a 30-g oral glucose, and during a hyperglycemic clamp. Insulin sensitivity was measured by a hyperinsulinemic- euglycemic clamp combined with isotope dilution. Partial pancreatectomy resulted in IFG and IGT. After partial pancreatectomy both basal and glucose-stimulated insulin secretion were decreased through the mechanism of a selective ∼50 and ∼80% deficit in insulin pulse mass, respectively (P < 0.05). These defects in insulin secretion were partially offset by decreased hepatic insulin clearance (P < 0.05). Partial pancreatectomy also caused a ∼40% decrease in insulin-stimulated glucose disposal (P < 0.05), insulin sensitivity after partial pancreatectomy being related to insulin pulse amplitude (r = 0.9, P < 0.01). We conclude that a ∼50% deficit in β-cell mass can recapitulate the alterations in glucose-mediated insulin secretion and insulin action in humans with IFG and IGT. These data support a mechanistic role of a deficit in β-cell mass in the evolution of IFG/IGT and subsequently type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)2347-2356
Number of pages10
JournalDiabetes
Volume55
Issue number8
DOIs
StatePublished - Aug 2006

Keywords

  • IFG, impaired fasting glucose
  • IGT, impaired glucose tolerance

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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