There is considerable evidence indicating that the secretory defect in non-insulin-dependent-diabetesmellitus is contributed to by a mis-regulation of beta cell intracellular pH, and can be corrected through pharmacological manipulation of intracellular pH. These hypotheses will be tested by comparing the regulation of intracellular pH in islets from healthy and diabetic animals, and monitoring insulin secretion from defective islets after pharmacological alteration of intracellular pH. The mechanisms of how intracellular pH influences insulin secretion is not known, and this will be investigated by monitoring changes in the production of reducing equivalents parallel to changes in intracellular pH and insulin secretion.
| Gunawardana, Subhadra C; Head, W Steven; Piston, David W (2008) Dimethyl amiloride improves glucose homeostasis in mouse models of type 2 diabetes. Am J Physiol Endocrinol Metab 294:E1097-108 |
| Hao, Mingming; Head, W Steven; Gunawardana, Subhadra C et al. (2007) Direct effect of cholesterol on insulin secretion: a novel mechanism for pancreatic beta-cell dysfunction. Diabetes 56:2328-38 |
| Gunawardana, Subhadra C; Rocheleau, Jonathan V; Head, W Steven et al. (2006) Mechanisms of time-dependent potentiation of insulin release: involvement of nitric oxide synthase. Diabetes 55:1029-33 |
