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
Diabetesjournal_title
Diabetesauthors
Matveyenko AV,Veldhuis JD,Butler PCdoi
10.2337/db06-0345subject
Has Abstractpub_date
2006-08-01 00:00:00pages
2347-56issue
8eissn
0012-1797issn
1939-327Xpii
55/8/2347journal_volume
55pub_type
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