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Reduced β-cell function contributes to impaired glucose tolerance in dogs made obese by high-fat feeding

1999; American Physiological Society; Volume: 277; Issue: 4 Linguagem: Inglês

10.1152/ajpendo.1999.277.4.e659

1522-1555

Karl J. Kaiyala, Ronald L. Prigeon, Steven E. Kahn, Stephen C. Woods, Daniel Porte, Michael W. Schwartz,

Diabetes Management and Research

The ability to increase β-cell function in the face of reduced insulin sensitivity is essential for normal glucose tolerance. Because high-fat feeding reduces both insulin sensitivity and glucose tolerance, we hypothesized that it also reduces β-cell compensation. To test this hypothesis, we used intravenous glucose tolerance testing with minimal model analysis to measure glucose tolerance ( K g ), insulin sensitivity (S I ), and the acute insulin response to glucose (AIR g ) in nine dogs fed a chow diet and again after 7 wk of high-fat feeding. Additionally, we measured the effect of consuming each diet on 24-h profiles of insulin and glucose. After high-fat feeding, S I decreased by 57% ( P = 0.003) but AIR g was unchanged. This absence of β-cell compensation to insulin resistance contributed to a 41% reduction of K g ( P = 0.003) and abolished the normal hyperbolic relationship between AIR g and S I observed at baseline. High-fat feeding also elicited a 44% lower 24-h insulin level ( P = 0.004) in association with an 8% reduction of glucose ( P = 0.0003). We conclude that high-fat feeding causes insulin resistance that is not compensated for by increased insulin secretion and that this contributes to the development of glucose intolerance. These effects of high-fat feeding may be especially deleterious to individuals predisposed to type 2 diabetes mellitus.