Resting beta-cells to reduce their metabolic demand and improve enduring glycaemic control
Description: Type 2 diabetes is characterised by a gradual reduction in beta-cell mass and function over time. Therefore, treatment regimens to reverse or prevent beta-cell dysfunction are highly sought after. We and others have demonstrated that beta-cell rest can significantly preserve beta-cell function over time, by reducing oxidative stress and workload. In this regard, we now know that Pancreatic Polypeptide (PP) induces beta-cell rest and also independently enhances beta-cell proliferation to apoptosis ratio. Given that clinically approved glucagon-like peptide-1 (GLP-1) mimetics are known to stimulate insulin secretion whilst also enhancing beta-cell survival, appropriate sequential administration of both agents could yield significant benefits. Based on this information and to progress a new approach to diabetes therapy that will preserve the function of islets, we need to understand: (i) if beta-cell rest with our long-acting, enzymatically stable, PP analogue can improve diabetes control and what are the related underlying mechanisms, (ii) if positive effects are sustainable and apparent at all stages of diabetes and (iii) whether induction of beta-cell rest can be improved with sequential liraglutide administration. Together, this research represents a crucial step in providing a scientific basis for development of an effective therapeutic regimen for people living with diabetes.
Funder: Diabetes UK
Amount: £285,100
Funding type: research
Funder scheme: Project Grant
Start date: 2023-03-01
End date: 2026-02-28
Investigators: Nigel Irwin, Nigel Irwin
Institution: University of Ulster
Funded outputs count: 3
Funder award ID: 22/0006448
OpenAlex ID: G1892580305