Abstract
BackgroundCalpain-10 was the first gene to be identified influencing the risk of type 2 diabetes (T2D) by positioning cloning. Studies in β-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 FindingsCalpain-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.ConclusionsWhile 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.
Highlights
Impaired insulin secretion from pancreatic b-cells together with insulin resistance in peripheral tissues represent hallmarks of type 2 diabetes (T2D)
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
The aims of the present study were to 1) analyze calpain-10 expression in pancreatic islets from multi-organ donors with and without T2D, 2) examine if two polymorphisms (SNP-43 and SNP44) in the CAPN10 gene are associated with gene expression and insulin secretion in human islets and 3) test if calpain-10 expression is associated with insulin secretion in human islets
Summary
Impaired insulin secretion from pancreatic b-cells together with insulin resistance in peripheral tissues represent hallmarks of type 2 diabetes (T2D). Common variants in the CAPN10 gene have been associated with transcript levels in skeletal muscle and adipose tissue [9,11,17]. The aims of the present study were to 1) analyze calpain-10 expression in pancreatic islets from multi-organ donors with and without T2D, 2) examine if two polymorphisms (SNP-43 and SNP44) in the CAPN10 gene are associated with gene expression and insulin secretion in human islets and 3) test if calpain-10 expression is associated with insulin secretion in human islets. Studies in b-cell lines and rodent islets suggest that calpain-10 may act as a regulator of insulin secretion. We tested if polymorphisms in the CAPN10 gene are associated with gene expression and insulin secretion in vitro
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