ALK7 signalling and insulin secretion.
Research type
Research Study
Full title
Deciphering the role of ALK7 signalling in the regulation of insulin secretion and type 2 diabetes risk.
IRAS ID
351581
Contact name
Constantinos Christodoulides
Contact email
Sponsor organisation
University of Oxford / Research Governance, Ethics and Assurance
Duration of Study in the UK
4 years, 3 months, 30 days
Research summary
Recent large-scale genetic studies have shown that individuals with rare DNA variants in the ACVR1C gene - expressed in both fat cells and pancreatic beta cells - and the INHBE gene, which is uniquely expressed in the liver, exhibit a reduced risk of developing type 2 diabetes (T2D). Animal and cell studies further suggest that ACVR1C and INHBE might function as a receptor-ligand pair, potentially establishing a communication pathway between the liver, fat cells, and pancreas that plays a role in regulating fat storage and insulin secretion. This study aims to understand how these genes modulate T2D risk by investigating insulin secretion in individuals with rare INHBE and ACVR1C gene variants. The study will include up to 15 participants with rare DNA variants in ACVR1C, 15 with INHBE variants, and 30 control participants without these variants. All participants will undergo assessments through an oral glucose tolerance test and the hyperglycaemic clamp technique, which involves ingesting an oral glucose load and controlled glucose infusions respectively to examine how the pancreas modulates insulin release in response to elevated blood glucose levels. By elucidating how ACVR1C and INHBE influence T2D susceptibility, this study aims to identify new therapeutic targets, potentially leading to more effective treatments for managing T2D through enhanced insulin secretion.
REC name
West Midlands - Black Country Research Ethics Committee
REC reference
25/WM/0063
Date of REC Opinion
15 May 2025
REC opinion
Further Information Favourable Opinion