Amino acid polymorphism Gly 972 Arg in IRS-1 is not associated to lower clamp-derived insulin sensitivity in young healthy first degree relatives of patients with type 2 diabetes

Insulin resistance is a complex metabolic disorder implicated in the development of many chronic diseases. While it is generally accepted that body mass loss should be the primary approach for the management of insulin resistance-related disorders in overweight and obese individuals, there is no consensus among researchers regarding optimal protein intake during dietary restriction. Recently, it has been suggested that increased plasma branched-chain amino acids concentrations are associated with the development of insulin resistance and type 2 diabetes. The exact mechanism by which excessive amino acid availability may contribute to insulin resistance has not been fully investigated. However, it has been hypothesised that mammalian target of rapamycin (mTOR) complex 1 hyperactivation in the presence of amino acid overload contributes to reduced insulin-stimulated glucose uptake because of insulin receptor substrate (IRS) degradation and reduced Akt-AS160 activity. In addition, the long-term effects of high-protein diets on insulin sensitivity during both weight-stable and weight-loss conditions require more research. This review focusses on the effects of high-protein diets on insulin sensitivity and discusses the potential mechanisms by which dietary amino acids can affect insulin signalling. Novelty: Excess amino acids may over-activate mTOR, resulting in desensitisation of IRS-1 and reduced insulin-mediated glucose uptake.

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The effect of exercise, training, and inactivity on insulin sensitivity in diabetics and their relatives: what is new?

Applied Physiology Nutrition and Metabolism ◽

10.1139/h07-031 ◽

2007 ◽

Vol 32 (3) ◽

pp. 541-548 ◽

Cited By ~ 23

Author(s):

Torben Østergård ◽

Niels Jessen ◽

Ole Schmitz ◽

Lawrence J. Mandarino

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Fatty Acids ◽

Insulin Sensitivity ◽

Exercise Training ◽

Large Scale ◽

High Energy ◽

First Degree Relatives ◽

Type 2 Diabetics

Insulin resistance is a hallmark characteristic of type 2 diabetes. However, in healthy first-degree relatives of type 2 diabetics, insulin resistance is often present years before glucose intolerance or diabetes becomes clinically manifest. The mechanisms of insulin resistance involve conditions leading to an increased supply of fatty acids (e.g., high energy intake, obesity) and conditions in which the degradation/oxidation of muscular fatty acids is impaired. Several large-scale studies have documented the fact that increased physical activity can reduce or at least postpone the development of type 2 diabetes, and low physical fitness is a clear independent risk factor for the development of type 2 diabetes. The mechanisms responsible for the improvement in insulin sensitivity after exercise training have been studied extensively, but are not fully understood. This review focuses on insulin resistance in skeletal muscle and, in particular, its relation to changes in aerobic fitness in type 2 diabetics and their first-degree relatives.

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