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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: Publikationen MPI-CBG 2010-arch     Display Documents

ID: 546552.0, MPI für molekulare Zellbiologie und Genetik / Publikationen MPI-CBG 2010-arch
Impaired insulin turnover in islets from type 2 diabetic patients.
Authors:Ehehalt, Florian; Knoch, Klaus-Peter; Erdmann, Katja; Krautz, Christian; Jäger, Melanie; Steffen, Anja; Wegbrod, Carolin; Meisterfeld, Ronny; Kersting, Stephan; Bergert, Hendrik; Kuhlisch, Eberhard; Bornstein, Stefan R.; Bonifacio, Enzio; Saeger, Hans-Detlev; Solimena, Michele
Date of Publication (YYYY-MM-DD):2010
Title of Journal:Islets
Issue / Number:1
Start Page:30
End Page:36
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Failure of pancreatic β-cells contributes to the development of type 2 diabetes. Besides evidence of reduced glucose-stimulated insulin secretion and β-cell mass, little information is available about the molecular deficits of human diabetic islets. Islets were isolated from macroscopically normal pancreatic tissue from 8 patients with type 2 diabetes and 17 matched non-diabetic patients who underwent pancreatic surgery. Insulin content and insulin secretion were measured before and after islet stimulation with 25 mM glucose for 2 hours. In parallel, we also investigated the subcellular localization of polypyrimidine tract-binding protein 1 (PTBP1), whose nucleocytoplasmic translocation is involved in the rapid posttranscriptional up-regulation of insulin biosynthesis following islet stimulation with glucose and GLP-1. Glucose stimulated insulin secretion was decreased, albeit not significantly, in type 2 diabetic islets compared to non-diabetic islets. Stimulation increased the total amount of insulin (islet insulin content + secreted insulin) in islet preparation from non-diabetic patients, but not from type 2 diabetic subjects. Furthermore, the nuclear levels of PTBP1 were decreased in stimulated non-diabetic islets, but not in type 2 diabetic islets. These results suggest that impairment of rapid insulin increase in response to glucose is a specific trait of type 2 diabetic islets. Nuclear retention of PTBP1 is likely to play a role in this deficit, which in turn can contribute to impaired insulin secretion in type 2 diabetes. Overall, these data highlight the importance of investigating mechanisms of insulin biosynthesis and degradation to gain insight into the pathogenesis of type 2 diabetes.
External Publication Status:published
Document Type:Article
Communicated by:nn
Affiliations:MPI für molekulare Zellbiologie und Genetik
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