Calpain facilitates actin reorganization during glucose-stimulated insulin secretion.
Calpain-10 (CAPN10) has been identified as a diabetes susceptibility gene. Previous studies have shown that alterations in calpain activity alter both glucose uptake and insulin secretion. In this report, we investigated the role of calpain activity in the actin reorganization required for glucose-stimulated insulin secretion. In pancreatic INS-1 cells, acute exposure to a high glucose environment stimulated CAPN10 gene expression with a concomitant increase in calpain activity. However, high glucose did not significantly alter expression of the two major ubiquitously expressed calpain family members, CAPN1 and CAPN2. Furthermore, glucose stimulation resulted in the reorganization of actin and inhibition of calpain activity impaired this reorganization in INS-1 cells. Finally, we identified a 54 kDa isoform as the major CAPN10 isoform that associates with the actin cytoskeleton. Based on our findings, we propose that calpain plays a role in facilitating the actin reorganization required for glucose-stimulated insulin secretion in INS-1 cells.
Turner
Mark D
MD
Centre for Diabetes and Metabolic Medicine, Institute of Cell and Molecular Science, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, Whitechapel, London E1 2AT, UK. M.D.Turner@qmul.ac.uk
Fulcher
F Kent
FK
Jones
Cristina V
CV
Smith
Bethany T
BT
Aganna
Ebun
E
Partridge
Christopher J
CJ
Hitman
Graham A
GA
Clark
Anne
A
Patel
Yashomati M
YM
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002154:Calpain / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
D000199:Actins; D007328:Insulin; D002154:Calpain; C415197:calpain 10; D005947:Glucose