Diet-Induced Type II Diabetes in C57BL/6J Mice

TLDR

The study examined how diet‑induced obesity affects glucose metabolism in C57BL/6J and A/J mice. Twenty mice per strain were fed either a high‑fat, high‑simple‑carbohydrate diet or standard chow for six months. High‑fat diet induced obesity in both strains, but only C57BL/6J mice developed severe type II diabetes with fasting glucose >240 mg/dl, hyperinsulinemia, and exaggerated stress‑induced glycemic responses, indicating a genetic predisposition and suggesting adrenergic‑response dysregulation as a potential biomarker.

Abstract

We investigated the effects of diet-induced obesity on glucose metabolism in two strains of mice, C57BL/6J and A/J. Twenty animals from each strain received ad libitum exposure to a high–fat high-simple-carbohydrate diet or standard Purina Rodent Chow for 6 mo. Exposure to the high-fat, high-simple-carbohydrate, low-fiber diet produced obesity in both A/J and C57BL/6J mice. Whereas obesity was associated with only moderate glucose intolerance and insulin resistance in A/J mice, obese C57BL/6J mice showed clear-cut diabetes with fasting blood glucose levels of >240 mg/dl and blood insulin levels of >150 μU/ml. C57BL/6J mice showed larger glycemic responses to stress and epinephrine in the lean state than AJ mice, and these responses were exaggerated by obesity. These data suggest that the C57BL/6J mouse carries a genetic predisposition to develop non-insulin-dependent (type II) diabetes. Futhermore, altered glycemic response to adrenergic stimulation may be a biologic marker for this genetic predisposition to develop type II diabetes.