Mechanisms of reversible lipotoxicity of the pancreas in T2 diabetes

• Research type

  Research Study

• Full title

  Mechanisms mediating reversible lipotoxicity of the pancreas in obesity-induced type 2 diabetes

• IRAS ID

  324459

• Contact name

  Ahmad Al-Mrabeh

• Contact email

  ahmad.al-mrabeh@ed.ac.uk

• Sponsor organisation

  University of Edinburgh

• Duration of Study in the UK

  5 years, 0 months, 0 days

• Research summary

  “Why did I develop type 2 diabetes (T2D) even though I’m not as heavy as my friends who did not?” This is a common question in diabetes clinics that remains a puzzle for long time. Although it is not the cause, obesity is a major risk factor. T2D can be reversed by dietary weight loss (~10%) intervention. However, this approach is challenging from the perspective of compliance because it involves following a low-calorie diet and avoiding weight regain. In addition, this approach does not suit everybody including those with normal body weight.
  
  The precise changes in lipid (fat) metabolism leading to pancreas failure to secrete adequate insulin and the mechanisms by which this is weight loss reverses this process are unknown. The main objective of this project is to understand how weight loss restores normal pancreas function in secreting insulin to develop novel therapies for remission. To answer these critical questions, I will investigate how weight loss, achieved by low calorie diet, changes fat delivery to the pancreas and restores pancreas mass and function. A particular focus of this project is the de novo lipogenesis process [DNL: conversion of sugar by the liver into fat]. I will use cutting-edge technologies [labelled isotopes/ advanced non-invasive MRI] to identify the potential toxic lipids. In addition, I aim to clarify whether remission of diabetes improves the capacity of adipose tissues to store fat safely away from the liver and pancreas tissues, whereas those who remains diabetics have altered adipose tissue function. Collectively, this will identify the precise sequence of events leading to pancreas lipotoxicity (dysfunction by excess fat build-up) and development of T2D. It will open new avenues towards novel more targeted therapies for remission of diabetes.

• REC name

  North West - Greater Manchester West Research Ethics Committee

• REC reference

  23/NW/0368

• Date of REC Opinion

  19 Dec 2023

• REC opinion

  Further Information Favourable Opinion