The Role of Phospholipase D in Regulating Insulin Secretion

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/376024

Funding Status
Closed

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Funded Activity Summary

Insulin, secreted appropriately by the b-cell of the pancreatic islets of Langerhans, regulates blood glucose levels through its effects on various tissues throughout the body. Precise control of insulin secretion from the pancreatic b-cell into the blood is therefore vital for accurate glucose homeostasis. Type II Diabetes Mellitus is caused by the inability of pancreatic b-cells to respond adequately to changes in blood glucose. In the last 18 months we have determined that the enzyme phospholipase D (PLD) plays an essential role in distally coordinating signals leading to accurately regulated insulin secretion from the pancreatic b-cell. Through this proposal we now aim to define the signalling pathways upstream of PLD and identify the mechanism downstream that allows PLD activity to regulate insulin secretion. We aim to use a combination of established and novel, biochemical and cell biological, approaches to characterize the role PKC alpha and beta isoforms and the small GTPase cdc42 may have in controlling PLD mediated insulin release. We will also use a variety of cell biological approaches to identify why, where, and when PLD activation is required for appropriate insulin secretion. We will also correlate these observations with the role the cell cytoskeleton may have in mediating PKC, cdc42 and-or PLD effects. In particular we aim to use a state-of-the-art microscope facility recently established at the Garvan Institute to achieve these aims. In doing this we will gain new insights into the pathways determining how insulin is released into the bloodstream, further define cellular processes common to all vesicular trafficking events and also identify potential targets for pharmacological intervention in the disease Diabetes.

Funded Activity Details

Start Date: 01-01-2006

End Date: 01-01-2008

Funding Scheme: NHMRC Project Grants

Funding Amount: $509,267.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Biochemistry and Molecular Biology | Diabetes (Type 2) | Islet of Langerhans | Phospholipase D | Protein Kinase C | exocytosis | insulin | membrane phospholipids

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