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Understanding the role of GLP-1

Project summary

Regulation of glucagon secretion by GLP-1: a role for GLP (9-36) mediated by a novel GLP-1 receptor?

GLP-1 is a potential therapy for diabetes because it increases insulin production and reduces production of glucagon, a hormone that elevates blood glucose. Dr Ramracheya will study islets in the lab to uncover the mechanisms involved in GLP-1 action.

Background to research

The high blood glucose levels experienced in Type 1 and Type 2 diabetes result from insufficient release of insulin combined with over-production of glucagon. Glucagon is a hormone produced by alpha-cells in the pancreas that increases blood glucose by causing glucose to be released from stores in the liver. Glucagon-like peptide-1 (GLP-1) is a hormone that has great potential as a treatment for diabetes because it increases insulin production and reduces the production of glucagon. Currently GLP-1 itself, drugs similar to GLP-1 (such as Byetta) and drugs that prevent the breakdown of GLP-1 (such as Sitagliptin) are used to help manage blood glucose in people with diabetes. The mechanisms by which GLP-1 improves insulin production are well-understood but much less is known about the mechanisms by which GLP-1 inhibits glucagon production and how these vary in diabetes.

Research aims

Dr Ramracheya aims to uncover GLP-1-related effects on the release of glucagon from islets in the pancreas and will find out if these effects involve an as yet unidentified receptor for GLP-1. This will involve studying the effects of GLP-1 on electrical activity and chemical signalling in alpha cells of the pancreas, finding out if alpha cells contain a GLP-1 receptor distinct from the one in beta cells, performing studies to work out the molecular structure of the receptor and studying the signalling mechanisms that work to stop glucagon release. Her work will involve studying isolated human islets in the laboratory and comparing the effects of GLP-1 with drugs that mimic the effects of GLP-1 

Potential benefit to people with diabetes

The role of the hormone glucagon in the management of diabetes has so far been largely overlooked in the search for new therapies to increase insulin production. In the long term, findings from this Fellowship could lead to the development of new therapies for accurately targeting the overproduction of glucagon in both Type 1 and Type 2 diabetes.

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