There are two major objectives of this research proposal for a Fogarty Senior International Fellowship. l. For the applicant to learn electrophysiology and patchclamping so as to enhance his research ability in the future and, in particular, to be able to take the next logical steps in his current studies on the mechanisms of action of inhibitors of insulin secretion. 2. To begin to understand the signal transduction mechanisms controlling insulin secretion in the human (Beta-cell with particular emphasis on the actions of inhibitors such as norepinephrine and somatostatin. Both of these objectives will be achieved by studying the properties of the KATP channel in the human (Beta-cell, and by determining which of the pertussis toxin sensitive heterotrimeric G-proteins mediate the activation of the channel by the inhibitors in their action to hyperpolarise the cell membrane. These studies will be of value to our understanding of Diabetes.
Straub, S G; Cosgrove, K E; Ammala, C et al. (2001) Hyperinsulinism of infancy: the regulated release of insulin by KATP channel-independent pathways. Diabetes 50:329-39 |
Straub, S G; James, R F; Dunne, M J et al. (1998) Glucose augmentation of mastoparan-stimulated insulin secretion in rat and human pancreatic islets. Diabetes 47:1053-7 |
Straub, S G; James, R F; Dunne, M J et al. (1998) Glucose activates both K(ATP) channel-dependent and K(ATP) channel-independent signaling pathways in human islets. Diabetes 47:758-63 |