Pulsatile Insulin Secretion: Detection, Regulation, and Role in Diabetes

Abstract

Insulin concentrations oscillate at a periodicity of 5-15 min per oscillation. These oscillations are due to coordinate insulin secretory bursts, from millions of islets. The generation of common secretory bursts requires strong within-islet and within-pancreas coordination to synchronize the secretory activity from the beta-cell population. The overall contribution of this pulsatile mechanism dominates and accounts for the majority of insulin release. This review discusses the methods involved in the detection and quantification of periodicities and individual secretory bursts. The mechanism by which overall insulin secretion is regulated through changes in the pulsatile component is discussed for nerves, metabolites, hormones, and drugs. The impaired pulsatile secretion of insulin in type 2 diabetes has resulted in much focus on the impact of the insulin delivery pattern on insulin action, and improved action from oscillatory insulin exposure is demonstrated on liver, muscle, and adipose tissues. Therefore, not only is the dominant regulation of insulin through changes in secretory burst mass and amplitude, but the changes may affect insulin action. Finally, the role of impaired pulsatile release in early type 2 diabetes suggests a predictive value of studies on insulin pulsatility in the development of this disease.