Mechanisms underlying the metabolic and vasodilator effects of insulin

Stride, Ann Elizabeth (2013). Mechanisms underlying the metabolic and vasodilator effects of insulin. University of Birmingham. Ph.D.

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Abstract

Insulin causes uptake of glucose into cells and also causes increases in skeletal muscle blood flow by vasodilatation. In order for insulin to act at receptors on the skeletal muscle membrane, it must move through the capillary endothelium. In conditions associated with insulin resistance, insulin-induced glucose uptake and vasodilatation are often blunted and disordered transport across endothelium has been suggested.
Firstly, studies were conducted using the hyperinsulinaemic euglycaemic (HE) clamp in rats to assess the relationship between insulin-induced muscle vasodilatation and glucose uptake into skeletal muscle. Insulin-induced vasodilatation was abolished by nitric oxide (NO) synthase inhibition in Wistar rats, implicating NO. Nutritional status and hence availability of glucose also affected vasodilatation in Wistar rats, leading to the proposal that vasodilatation was linked to glucose metabolism.
Vasodilator response to insulin was significantly higher in lean versus obese Zucker rats. Nicotinic acid (NAc) did not decrease plasma FFA concentrations versus HE clamp, nevertheless, vasodilator response and glucose uptake were enhanced in lean and obese rats by some mechanism other than lowering FFA.
Optimisation of the microdialysis technique allowed measurement, for the first time, of interstitial insulin concentrations in lean and obese Zucker rats and showed a significant difference under basal conditions.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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