Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle - PubMed (original) (raw)

Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle

J K Kim et al. J Clin Invest. 2000 Jun.

Abstract

Obesity and insulin resistance in skeletal muscle are two major factors in the pathogenesis of type 2 diabetes. Mice with muscle-specific inactivation of the insulin receptor gene (MIRKO) are normoglycemic but have increased fat mass. To identify the potential mechanism for this important association, we examined insulin action in specific tissues of MIRKO and control mice under hyperinsulinemic-euglycemic conditions. We found that insulin-stimulated muscle glucose transport and glycogen synthesis were decreased by about 80% in MIRKO mice, whereas insulin-stimulated fat glucose transport was increased threefold in MIRKO mice. These data demonstrate that selective insulin resistance in muscle promotes redistribution of substrates to adipose tissue thereby contributing to increased adiposity and development of the prediabetic syndrome.

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Figures

Figure 1

(a) Steady-state glucose infusion rate, obtained from averaged rates of 90–120 minutes of hyperinsulinemic-euglycemic clamps, in the control group and MIRKO group. (b) Hepatic glucose production during the insulin-stimulated state in the control group and MIRKO group. Values are means ± SE for eight or nine experiments. A_P_ < 0.05 versus control group.

Figure 2

Whole-body and skeletal muscle glucose transport and metabolism. (a) Insulin-stimulated whole-body glucose uptake, glycolysis, and glycogen/lipid synthesis in vivo in the control group and MIRKO group. (b) Insulin-stimulated glucose transport, glycolysis, and glycogen synthesis in skeletal muscle (gastrocnemius) in vivo in the control group and MIRKO group. Values are means ± SE for eight or nine experiments. A_P_ < 0.005 versus control group.

Figure 3

In vivo and in vitro glucose transport in adipose tissue. (a) Insulin-stimulated glucose transport in gastrocnemius muscle (left) and epididymal white adipose tissue (right) in vivo in the control group and MIRKO group. (b) Basal and insulin-stimulated glucose transport in isolated adipocytes in the control group and MIRKO group. Values are means ± SE for four to nine experiments. A_P_ < 0.005 versus control group.

Figure 4

Glucose metabolic flux in isolated adipocytes. (a) Basal (left) and insulin-stimulated (right) conversion of glucose into lactate in isolated adipocytes in the control group and MIRKO group. (b) Basal (left) and insulin-stimulated (right) conversion of glucose into triglyceride in isolated adipocytes in the control group and MIRKO group. (c) Basal (left) and insulin-stimulated (right) conversion of glucose into CO2 in isolated adipocytes in the control group and MIRKO group. Values are means ± SE for four or five experiments. A_P_ < 0.05 versus control group.

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Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle - PubMed (original) (raw)