Gut hormone combinations as a novel and effective treatment for obesity-related Type 2 diabetes
Description: Obesity is the biggest risk factor for Type 2 diabetes. The most effective treatment, bariatric surgery, produces a rise in gut hormones [glucagon-like peptide 1 (GLP-1), Peptide YY (PYY) and oxyntomodulin (OXM)]. I have convincingly recreated the weight loss and diabetes remission achieved with surgery by injecting these hormones in combination to obese rodents. I have demonstrated an elevation in energy expenditure, which is key to sustained weight loss, and suggested direct effects on the pancreatic β cell to enhance insulin release. Combination gut hormone therapies are in the pipeline to treat diabetes and obesity in humans, but their sites of action are not fully understood. I will introduce siRNA to regionally knockdown gut hormone responsiveness in the rodent nervous system, to tease out the pathways of action of gut hormones on energy expenditure and glucose homeostasis. I will use a novel imaging platform to longitudinally assess their combined effects on islet function, allowing me to assess the relative anti-hyperglycaemic effects of weight loss versus direct actions on the pancreatic β cell. Together this will inform the development of better targeted and safe combination hormonal treatments, designed to recreate the diabetes remission and sustained weight loss achieved with bariatric surgery.
Funder: Diabetes UK
Amount: £871,200
Funding type: fellowship
Funder scheme: Harry Keen Intermediate Fellowship
Start date: 2016-08-01
End date: 2021-07-31
Investigators: Salem, Salem
Institution: Imperial College London
Funded outputs count: 6
Funder award ID: 15/0005317
OpenAlex ID: G4983808301