A. M. Kressel1, S. Chavan1,2, K. J. Tracey1,2 1Northwell Health,Center For Biomedical Science,Manhasset, NY, USA 2Northwell Health,Center For Bioelectronic Medicine,Manhasset, NY, USA
Introduction: Diabetes and its sequelae are a significant cause of morbidity and mortality, affecting the lives of millions of people worldwide. Many current therapies for diabetes are aimed at lowering blood glucose. Evidence indicates that inappropriate hyperglucagonemia may contribute to the phenotype of diabetes, and is therefore a potential target for treatment. Under normal conditions, glucagon is released into the blood from α-cells in the pancreas in response to hypoglycemia and induces gluconeogenesis in the liver. Glucagon release from the pancreas may be subject to neural control, as the pancreas is innervated by the vagus nerve. However, the specific neurotransmitters involved are not yet completely understood. Here, we developed a bioassay and analyzed the effects of neurotransmitters on the islet response ex vivo.
Methods: Pancreatic islets were isolated from adult mice and maintained in culture. After a recovery period of 24 hours, islets were placed in a hypoglycemic environment and exposed to different neurotransmitters in a range of concentrations. They were then stimulated with acetylcholine to augment glucagon and insulin release. Supernatants were collected one hour later, and insulin and glucagon levels were quantified by ELISA.
Results: GABA and somatostatin were found to inhibit glucagon release from cultured pancreatic islets in a concentration-dependent manner.
Conclusion: These findings demonstrate that exogenous neurotransmitters attenuate glucagon release from pancreatic islets ex vivo in the setting of hypoglycemia and acetylcholine challenge.
