Research Summary

Human skeletal muscle intracellular signaling and insulin sensitivity: A study to understand the impact of life style intervention in pre diabetics.

The growing burden of type 2 diabetes mellitus in India is of concern. Insulin provides an integrated set of signals that allow balancing of glucose in the body. The primary targets of insulin action to maintain glucose homeostasis are skeletal muscle, liver, and adipose tissue. Among these, skeletal muscle is considered to be the largest insulin-sensitive organ. Reduced insulin sensitivity has been linked to muscle quality/functionality. Muscle contractile and metabolic “quality” depend on a number of factors, the former on contractile protein content and the latter on muscle fibre type composition (oxidative or glycolytic) relating to factors such as mitochondrial content and the amount of intramyocellular triglycerides.

Despite a normal body mass index, many Indians may be at risk of becoming insulin resistant, raising the possibility, that insulin resistance is related more to regional rather than general adiposity. Increased visceral fat in Indians is not often apparent from their body mass index, and has led to the terms “metabolic obesity” and “the thin-fat Indian”. Visceral fat is less sensitive to anti-lipolytic stimuli compared to subcutaneous fat. Therefore, it is more likely to release free fatty acids into the circulation, which may lead to ectopic fat storage in non adipose tissues like skeletal muscle. Fat storage in non adipose tissue could exist independent of generalized adiposity making it difficult to establish true associations between insulin resistance and body mass index. It is therefore critical to understand the role of non adipose tissue (especially muscle) in regulating insulin sensitivity, particularly in Indians. The present standard recommendations to either prevent or treat type 2 diabetes, are modifications in lifestyle habits. With a pre-existing low muscle mass, it will be very important to evaluate the impact of caloric restriction, protein supplementation and resistance exercise in regulating and maintaining insulin sensitivity in Indian population.

The overarching aim of the work outlined in this proposal is to increase our understanding of the role of skeletal muscle in the aetiology of type 2 diabetes in the Indian population and to evaluate the efficacy of interventions designed to target improvements in muscle mass, function and metabolic potential. A better understanding of the cause(s) of the predisposition of Indians to become diabetic will be very useful in planning healthcare policy and delivery in the coming years, in order to ensure that the burden of this disease is reduced.