Title:
Insight into Stimulus-Secretion Coupling of Pancreatic Beta-Cell

 

Mitsuhisa Komatsu, M.D., Ph.D
Division of Diabetes, Endocrinology and Metabolism Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto

 

Abstract:
Diabetes mellitus is characterized by chronic elevation of plasma glucose concentrations, and it frequently leads to serious complications. Insulin, which is secreted from pancreatic β-cell, is the unique hormone that lowers plasma glucose concentration, and the deterioration of insulin secretion causes to the elevation of plasma glucose concentration, and eventually diabetes. Here, I will focus on the mechanisms of insulin secretion in order to understand pathophysiology of diabetes mellitus. A complex network in the β-cells controls insulin secretion. Among various determinants, glucose and incretin hormones are major regulators of the rates of insulin secretion. Glucose stimulates insulin release via two distinct but mutually related pathways. Upon stimulation with glucose, ATP is produced by glucose metabolism and it causes membrane depolarization by closure of KATP channel that determine membrane potential of the β-cells. Membrane depolarization opens the voltage-dependent Ca2+ channels and causes Ca2+ influx, thereby elevating intracellular Ca2+ concentration. Eventually, the Ca2+-stimulated insulin release occurs. On the other hand, glucose metabolism expands the size of the pool of insulin secretory granules that respond to Ca2+ stimulation via metabolic signals independent from Ca2+ signaling. The former refers to as a KATP channel-dependent pathway, and the latter are collectively called the KATP channel-independent glucose action. We had established the presence of KATP-independent pathway for the first time. Since then, we have been exploring the molecular basis and characteristics behind them. I will introduce our history of research for stimulus-secretion coupling in pancreatic β-cell.

 

References:
Komatsu M et al. Glucose-stimulated insulin secretion: A newer perspective. J Diabetes Invest 2013, 4:511-6.

Ishii H et al. Glucose-incretin interaction revisited. Endocr J 2011, 58:519-25.