Project Details
Projekt
The insulin secretion in the pancreatic beta-cell under influence of different cannabinoid receptors and endocannabinoid metabolism
Subject Area
Endocrinology, Diabetology, Metabolism
Nuclear Medicine, Radiotherapy, Radiobiology
Nuclear Medicine, Radiotherapy, Radiobiology
Term
from 2017 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 386330389
The endocannabinoid system (ECS) consisted of cannabinoid receptors, enzymes for the synthesis and degradation and endogenous ligands, the so called endocannabinoids. The ECS influences neuronal signaling, as well as hormonal secretion of the pancreatic islet. The endocannabinoid system affects the activity of pancreatic beta-cells by modulation of insulin secretion. Different cannabinoid receptors coupled to intracellular signaling pathways mediate effects of endocannabinoids. However, little is known about the second messengers associated with these pathways.In the proposal we plan to the following aspects by using the well-established rat insulinoma beta beta cell model INS-1 and a newly characterized human beta cell model EndoC-betaH1, genetically modified variants of EndoC-betaH1, isolated human pancreatic islets and cannabinoid receptor knockout mice. We will focus on: (1) Participation of ECS on modulation of physiologically or diabetic stimulated insulin secretion, while simultaneously investigating the signaling components involved, and (2) the importance of endocannabinoid metabolism and the receptor alterations for regulating insulin secretion and type 2 diabetes.Prospectively, the proposed study might contribute to our knowledge of the impact of G-protein-coupled receptor signaling pathways in pancreatic islets and will shed new light on the role of the ECS for the insulin secretion. Actively influencing the ECS opens new options for the treatment of the clinically highly relevant disease of type 2 diabetes.
DFG Programme
Research Grants
