Function (biology)

Cell biology

Type 2 diabetes

Impaired glucose tolerance

Biology

Plasma glucose

Insulin response

Endocrinology

Insulin sensitivity

Insulin

Glucose tolerance test

Insulin tolerance test

Insulin resistance

Internal medicine

Medicine

Obesity

Carbohydrate metabolism

Diabetes mellitus

AJP Endocrinology and Metabolism

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.

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