Mechanisms of the amplifying pathway of insulin secretion in the β cell

Abstract

Pancreatic islet β cells secrete insulin in response to nutrient secretagogues, like glucose, dependent on calcium influx and nutrient metabolism. One of the most intriguing qualities of β cells is their ability to use metabolism to amplify the amount of secreted insulin independent of further alterations in intracellular calcium. Many years studying this amplifying process have shaped our current understanding of β cell stimulus-secretion coupling; yet, the exact mechanisms of amplification have been elusive. Recent studies utilizing metabolomics, computational modeling, and animal models have progressed our understanding of the metabolic amplifying pathway of insulin secretion from the β cell. New approaches will be discussed which offer in-roads to a more complete model of β cell function. The development of β cell therapeutics may be aided by such a model, facilitating the targeting of aspects of the metabolic amplifying pathway which are unique to the β cell.

Keywords: Amplifying pathway; Biphasic insulin secretion; Cell signaling; Glucose sensing; Metabolomics; Pancreatic islet beta cells.