Insulin's Role as a Vascular Hormone in Health and Disease

Cleland, Stephen Jackson (1998) Insulin's Role as a Vascular Hormone in Health and Disease. PhD thesis, University of Glasgow.

Abstract

A series of studies is described in which both clinical and basic techniques have been used to investigate insulin's role as a vascular hormone and the relationship of this to metabolic insulin sensitivity and vascular endothelial function. These techniques (described in chapter 2) have been used to investigate: the physiological mechanisms of insulin-mediated vasodilation (chapter 3); the relationship between insulin's metabolic and vascular actions (chapter 4); the effect on insulin sensitivity of induced endothelial dysfunction (chapter 5); the relationship between structural components of skeletal muscle and insulin action (chapter 6); the associations among insulin sensitivity, insulin vasodilation and basal endothelial function in insulin-resistant subjects (chapter 7); the sensitivity of platelets to agonist-induced aggregation with respect to different levels of insulin sensitivity (chapter 8); the role of immunogold electron microscopy in direct visualisation of GLUT4 translocation in skeletal muscle cells (chapter 9). Conclusions: Insulin is a vasoactive hormone. Mechanisms of insulin-mediated vasodilation include stimulation of endothelial NO production and membrane hyperpolarisation via stimulation of Na+K+ATPase. Insulin-mediated vasodilation occurs gradually over 40-50 minutes suggesting involvement of intermediate mechanisms. Cellular glucose uptake augments insulin-mediated vasodilation. Whole-body insulin-stimulated glucose uptake and local insulin/glucose vasodilation are functionally linked. Systemic inhibition of NO production does not impair whole-body insulin-mediated glucose uptake. Skeletal muscle capillary density is not associated with insulin's vascular action. Insulin resistance is not associated with increased sensitivity of washed platelets to thrombin-induced aggregation. Insulin-mediated vasodilation is preserved in older men but is blunted in parallel with reductions in insulin sensitivity. Vasoconstriction in response to local inhibition of NO synthase is delayed during hyperinsulinaemia compared with fasting conditions suggesting that insulin stimulates eNOS activity. Insulin sensitivity correlates with basal endothelial NO production in both young and older men. Insulin-mediated vasodilation correlates with basal endothelial NO production in older, but not in young men. Insulin's stimulation of endothelial NO production may be a key intermediate mechanism linking insulin sensitivity with basal endothelial function. (Abstract shortened by ProQuest.).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: John Connell
• Keywords: Medicine, Endocrinology
• Date of Award: 1998
• Depositing User: Enlighten Team
• Unique ID: glathesis:1998-75283
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 21:20
• Last Modified: 19 Nov 2019 21:20
• URI: https://theses.gla.ac.uk/id/eprint/75283