Research Theme

Diabetes and Metabolism

Diabetes and its associated complications, which include heart, kidney and eye disease, affect the quality of life of a large number of Australians. It is estimated that 940,000 Australians have diabetes and, about half of those are not aware that they have the condition. The number has doubled since the early 1980s and is expected to pass 1 million over the next 10 years unless effective strategies are put into place (Source: AIHW 2004).

Some examples of research projects within the Diabetes and Metabolism research theme at the Menzies Research Institute:

Control of muscle metabolism by microvascular perfusion

Our group continued to explore the relationship between insulin-mediated uptake of glucose by muscle and insulin-mediated increases in microvascular perfusion. We published three invited reviews in 2006 on factors influencing the hemodynamic and metabolic effects of insulin in muscle; nutritive blood flow as an essential element supporting muscle anabolism; and muscle metabolism and control of capillary blood flow relating to insulin and exercise.

Effect of the nitric oxide-dependent vasodilator on insulin action in muscle

Methacholine is a nitric-vasodilator but unlike other vasodilators, potentiates insulin-mediated glucose uptake by muscle. The present study aimed to resolve whether this action was the result of a vascular effect of methacholine to increase muscle perfusion or a direct effect of methacholine on the myocytes. We hypothesised that vascular-mediated insulin-stimulated glucose uptake responses to methacholine occur at lower doses than direct myocyte methacholine-mediated increase in glucose uptake.

We found that methacholine has dose-dependent effects both on the vasculature and on muscle metabolism. At low dose, methacholine is a potent vasodilator in muscle in vivo and in vitro without metabolic effects; at higher doses there is a direct metabolic effect of methacholine to increase glucose uptake.

Insulin-mediated vasoreactivity in skeletal muscle resistance arteries

This project was an external collaboration which investigated whether an inflammatory cytokine TNFalpha, that is elevated in the blood of type 2 diabetics, directly impaired insulin-mediated vasoreactivity in skeletal muscle arteries as well as examining the role of certain signalling kinases. TNFalpha was found to inhibit vasodilator but not vasoconstrictor effects and was mediated by the proposed kinase.

For more information, contact:

 

Associate Professor Steve Rattigan

Senior Member

Telephone: (03) 6226 2671