Understanding the mechanisms that regulate insulin secretion could lead to novel therapies for Type 1 and Type 2 diabetes. Two areas of interest focused on islet beta cells at Cedars-Sinai include:
- The role of anandamide, an endogenous cannabinoid receptor ligand, on insulin secretion
- The physiological relevance of islet size heterogeneity
Research is underway to elucidate the in vitro effects of anandamide on isolated pancreatic islets from lean and fat-fed animals using a canine model.
Another islet beta cell study is designed to ascertain why there are different-sized pancreatic islets and to determine whether small or large islets are primarily responsible for beta cell compensation in response to fat-diet-induced insulin resistance.
Orison Woolcott, MD, is a project scientist focused on both of these islet beta cell studies at Cedars-Sinai's Diabetes and Obesity Research Institute. Woolcott is using animal models to further understand the link between beta cell dysfunction, obesity and diabetes.
Current studies include:
- Beta cells' response to anandamide in diet-induced obesity
- Examine pancreatic islets in normal-fed and fat-fed animal models, focusing on beta cells.
- Work with islets in vitro to study effect of anandamide on beta cells.
- Explore possible mechanism of anandamide and whether it stimulates beta cells directly or through a secondary response.
- Compare response of beta cells to anandamide in normal-fed verses fat-fed models.
- Determine whether anandamide directly signals beta cells to produce insulin and, if so, how this occurs.
- Efficiency of large and small islets in diet-induced obesity
- Examine insulin secretion in large and small islets in both normal-fed and fat-fed animal models.
- Isolate islets for measurement and classify as small or large.
- Express beta cell function as the ratio of insulin secretion induced by glucose and as insulin units normalized to islet size.
- Determine whether larger or smaller islets compensate more for fat-induced insulin resistance.
Research that elucidates the mechanisms of insulin secretion can lead to breakthroughs for both Type 1 and Type 2 diabetes therapies. The link between the endocannabinoid system and pancreatic islet function is a relatively new frontier of study that may hold promise for creating therapies targeted to impaired pancreatic endocrine function. Understanding the physiological relevance of islet size heterogeneity also could help scientists identify medications aimed at specific islets for improved insulin production.