A Dash of Salt-Inducible Kinase 1 Keeps Insulin Levels in Check.

Abstract

The precise control of insulin release from pancreatic β-cells in response to changes in circulating glucose levels is essential for maintaining metabolic homeostasis. Understanding the pathways coupling insulin secretion to blood glucose levels is critical for the development of new strategies to treat a variety of metabolic disorders, including type 2 diabetes. In this issue of Diabetes , Kim et al. (1) propose a novel regulatory feedback mechanism operating within β-cells that acts to reduce insulin secretion. Within β-cells, cyclic AMP (cAMP) acts as a positive regulator of insulin secretion by both nontranscriptional and transcriptional mechanisms. Increased cAMP levels can directly potentiate insulin granule release, as well as regulate genes involved in β-cell function and survival (2–4). Thus, cAMP levels within β-cells must be tightly regulated in order to ensure proper secretion of adequate amounts of insulin. The importance of cAMP in type 2 diabetes is underscored by the proliferation of incretin-based drugs on the market over the past decade, including glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase-4 inhibitors, which potentiate insulin release by increasing cAMP signaling in β-cells (5). Thus, developing our understanding of the mechanisms controlling cAMP levels in β-cells has great potential to uncover new therapeutic …