Mechanisms of impaired fasting glucose and glucose intolerance induced by an approximate 50% pancreatectomy.

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. beta-Cell mass is approximately 50% deficient in IFG and approximately 65% deficient in type 2 diabetes. To establish the effect of a approximately 50% deficit in beta-cell mass on carbohydrate metabolism, we performed a approximately 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 approximately 50 and approximately 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 approximately 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 approximately 50% deficit in beta-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 beta-cell mass in the evolution of IFG/IGT and subsequently type 2 diabetes.

journal_name

Diabetes

journal_title

Diabetes

authors

Matveyenko AV,Veldhuis JD,Butler PC

doi

10.2337/db06-0345

subject

Has Abstract

pub_date

2006-08-01 00:00:00

pages

2347-56

issue

8

eissn

0012-1797

issn

1939-327X

pii

55/8/2347

journal_volume

55

pub_type

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