Abstract
In our westernised society, the level of physical activity is low. Interventions that increase energy expenditure are generally associated with an improvement in metabolic health. Exercise and exercise training increase energy metabolism and are considered to be among the best strategies for prevention of type 2 diabetes mellitus. More recently, cold exposure has been suggested to have a therapeutic value in type 2 diabetes. At a cellular level, there is evidence that increasing the turnover of cellular substrates such as fatty acids is associated with preventive effects against lipid-induced insulin resistance. Cellular energy sensors may underlie the effects linking energy turnover with metabolic health effects. Here we review data supporting the hypothesis that increasing energy and substrate turnover has beneficial effects on insulin sensitivity and should be considered a target for the prevention and treatment of type 2 diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-016-4068-3) contains a slideset of the figures for download, which is available to authorised users.
Highlights
Obesity is the major risk factor for the development of type 2 diabetes mellitus
Mitochondrial uncoupling or enhanced fatty acid turnover may occur, thereby preventing the negative effects of cellular substrate overload hypothesis, it was demonstrated by Schenk and Horowitz [63] that one bout of acute exercise could reverse lipid-induced insulin resistance in humans, and that this was accompanied by an increased partitioning of excess fatty acids towards triacylglycerol synthesis in muscle
Severe cold exposure in animals has been shown to increase lipolysis, lipid oxidation and NEFA turnover, as well as glucose oxidation and turnover, and thereby improves glucose tolerance and peripheral glucose uptake (Fig. 2) [87, 88]. These findings indicate that an increase in cold-induced shivering thermogenesis can have pronounced effects on glucose homeostasis; these studies were conducted under severe cold exposure, a condition that cannot be sustained for long periods of time
Summary
Obesity is the major risk factor for the development of type 2 diabetes mellitus. It is characterised by an increased storage of fat in subcutaneous white adipose tissue but is associated with increased storage of fat in non-adipose tissues, such as muscle and liver. We review the evidence, focusing on human intervention studies, suggesting that increasing energy turnover by exercise and/or cold exposure can offset obesity-related insulin resistance and be a preventive strategy for type 2 diabetes mellitus.
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