[Frontiers in Bioscience 16, 1197-1210, January 1, 2011]

Regulation of resident and newcomer insulin granules by calcium and SNARE proteins

Kyota Aoyagi, Mica Ohara-Imaizumi, Shinya Nagamatsu

Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo, 181-8611, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Overview of insulin secretion
3.1. Functional coupling between glucose stimulation and insulin secretion
3.2. Biphasic insulin secretion
3.3. Exocytotic process and SNARE functions
3.4. Current model for biphasic insulin secretion
4. Imaging analysis of insulin secretion
4.1. TIRF microscopy
4.2. Application of TIRF microscopy to imaging analysis of dynamics of secretory granules
4.3. Docked granules detected by electron and TIRF microscopies
4.4. Analysis of biphasic insulin secretion by TIRF microscopy
4.5. Relationship between SNARE proteins and biphasic insulin release
4.6. Second phase insulin release and fusions from newcomer granules
4.7. Different characteristics of Ca2+ sensing in previously docked and newcomer granules
4.8. Regulation of second phase insulin release by phosphatidylinositol 3-kinase
4.9. Akt substrates, possible regulator of second phase insulin secretion
5. Proposed model for biphasic insulin secretion
6. Acknowledgment
7. References

1. ABSTRACT

Insulin, stored in large dense core granules, is biphasically exocytosed by glucose stimulation in pancreatic beta-cells. Several molecules, such as SNARE proteins, and Ca2+ ion are involved in the regulation of insulin exocytosis. 　Indeed, studies using gene targeting mice revealed critical roles of SNARE proteins and their accessory proteins, which may be associated with diabetes mellitus. In particular, the total internal reflection fluorescent (TIRF) imaging technique shed new light on the molecular mechanism of the insulin exocytotic process. In this review we discuss the mechanism of insulin exocytosis mainly from a point of view of imaging techniques.