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FP7

BRIDIT Result In Brief

Project ID: 622612
Funded under: FP7-PEOPLE
Country: United Kingdom

Beta-cell receptors for diabetes

Diabetes is a chronic metabolic disorder affecting millions of Europeans. EU researchers investigated the role of G-protein coupled receptors (GPCRs) in glucose homeostasis to find novel solutions without unpleasant side-effects.
Beta-cell receptors for diabetes
Type 2 diabetes is a condition where the β-cells in the islets of Langerhans in the pancreas are unable to produce enough insulin to regulate blood glucose levels. This is attributed to impaired insulin secretion and/or reduced β-cell mass. Some drugs currently used to treat diabetes target the GPCRs in the islets but these drugs also have undesirable side effects.

Using cutting edge islet biology methodologies, the two-year project BRIDIT (Beta-cell receptors in diabetes therapy) investigated the role of the GPCRs – FFAR2 and FFAR3 in β-cell function in response to short-chain fatty acids (SCFAs). Researchers also studied other islet GPCRs such as GPR55 and peptide YY to determine their role in regulating insulin secretion.

Study outcomes revealed that SCFAs directly activate the FFAR2 receptors on the islets of Langerhans β-cells and stimulate insulin release. Acetate and propionate were successfully used to potentiate insulin secretion and protect β-cells from cytotoxic and lipotoxic insults. Using mice models deficient in FFAR2, BRIDIT demonstrated that FFAR2 is required to facilitate the effects of acetate and propionate. These results indicate that targeting the FFAR2 receptor for diabetes therapy could prove effective.

BRIDIT researchers found that a GPR55 agonist stimulates glucose-dependent insulin secretion and protects islets from undergoing apoptosis.

Overall, the BRIDIT study has provided important information on GPCRs and their ability to increase insulin secretion, stimulate β-cell proliferation or protect β-cells from undergoing apoptosis. Targeting FFAR2 or GPR55 could prove to be effective in diabetes treatment.

Related information

Keywords

Diabetes, GPCR, glucose homeostasis, insulin secretion, β-cell mass, BRIDIT, islet biology, FFAR2
Record Number: 190753 / Last updated on: 2016-12-20
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