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Calpain-10 expression is elevated in pancreatic islets from patients with type 2 diabetes.

Ling, Charlotte LU ; Groop, Leif LU ; Guerra, Silvia Del and Lupi, Roberto (2009) In PLoS ONE 4(8).
Abstract
BACKGROUND: Calpain-10 was the first gene to be identified influencing the risk of type 2 diabetes (T2D) by positioning cloning. Studies in beta-cell lines and rodent islets suggest that calpain-10 may act as a regulator of insulin secretion. However, its role in human pancreatic islets remains unclear. The aim of this study was to examine if calpain-10 expression is altered in islets from patients with T2D and if the transcript level correlates with insulin release. We also tested if polymorphisms in the CAPN10 gene are associated with gene expression and insulin secretion in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Calpain-10 mRNA expression was analysed in human pancreatic islets from 34 non-diabetic and 10 T2D multi-organ donors. CAPN10... (More)
BACKGROUND: Calpain-10 was the first gene to be identified influencing the risk of type 2 diabetes (T2D) by positioning cloning. Studies in beta-cell lines and rodent islets suggest that calpain-10 may act as a regulator of insulin secretion. However, its role in human pancreatic islets remains unclear. The aim of this study was to examine if calpain-10 expression is altered in islets from patients with T2D and if the transcript level correlates with insulin release. We also tested if polymorphisms in the CAPN10 gene are associated with gene expression and insulin secretion in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Calpain-10 mRNA expression was analysed in human pancreatic islets from 34 non-diabetic and 10 T2D multi-organ donors. CAPN10 SNP-43 and SNP-44 were genotyped and related to gene expression and insulin release in response to glucose, arginine and glibenclamide. The mRNA level of calpain-10 was elevated by 64% in pancreatic islets from patients with T2D compared with non-diabetic donors (P = 0.01). Moreover, the calpain-10 expression correlated positively with arginine-stimulated insulin release in islets from non-diabetic donors (r = 0.45, P = 0.015). However, this correlation was lost in islets from patients with T2D (r = 0.09; P = 0.8). The G/G variant of SNP-43 was associated with reduced insulin release in response to glucose (P</=0.04) in non-diabetic donors. CONCLUSIONS: While calpain-10 expression correlates with insulin release in non-diabetic human islets, this correlation is lost in T2D suggesting that a stimulatory effect of calpain-10 could be lost in patients with T2D. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
4
issue
8
publisher
Public Library of Science
external identifiers
  • wos:000269075800002
  • pmid:19688040
  • scopus:68949213757
ISSN
1932-6203
DOI
10.1371/journal.pone.0006558
language
English
LU publication?
yes
id
6c7d38fb-33fe-4d9a-a106-0290f1b818c0 (old id 1469633)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19688040?dopt=Abstract
date added to LUP
2009-09-07 14:25:59
date last changed
2017-07-23 04:58:08
@article{6c7d38fb-33fe-4d9a-a106-0290f1b818c0,
  abstract     = {BACKGROUND: Calpain-10 was the first gene to be identified influencing the risk of type 2 diabetes (T2D) by positioning cloning. Studies in beta-cell lines and rodent islets suggest that calpain-10 may act as a regulator of insulin secretion. However, its role in human pancreatic islets remains unclear. The aim of this study was to examine if calpain-10 expression is altered in islets from patients with T2D and if the transcript level correlates with insulin release. We also tested if polymorphisms in the CAPN10 gene are associated with gene expression and insulin secretion in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Calpain-10 mRNA expression was analysed in human pancreatic islets from 34 non-diabetic and 10 T2D multi-organ donors. CAPN10 SNP-43 and SNP-44 were genotyped and related to gene expression and insulin release in response to glucose, arginine and glibenclamide. The mRNA level of calpain-10 was elevated by 64% in pancreatic islets from patients with T2D compared with non-diabetic donors (P = 0.01). Moreover, the calpain-10 expression correlated positively with arginine-stimulated insulin release in islets from non-diabetic donors (r = 0.45, P = 0.015). However, this correlation was lost in islets from patients with T2D (r = 0.09; P = 0.8). The G/G variant of SNP-43 was associated with reduced insulin release in response to glucose (P&lt;/=0.04) in non-diabetic donors. CONCLUSIONS: While calpain-10 expression correlates with insulin release in non-diabetic human islets, this correlation is lost in T2D suggesting that a stimulatory effect of calpain-10 could be lost in patients with T2D.},
  articleno    = {e6558},
  author       = {Ling, Charlotte and Groop, Leif and Guerra, Silvia Del and Lupi, Roberto},
  issn         = {1932-6203},
  language     = {eng},
  number       = {8},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Calpain-10 expression is elevated in pancreatic islets from patients with type 2 diabetes.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0006558},
  volume       = {4},
  year         = {2009},
}