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Ehehalt, F.* ; Knoch, K.P.* ; Erdmann, K.* ; Krautz, C.* ; Jäger, M.* ; Steffen, A.* ; Wegbrod, C.* ; Meisterfeld, R.* ; Kersting, S.* ; Bergert, H.* ; Kuhlisch, E.* ; Bornstein, S.* ; Bonifacio, E.* ; Saeger, H.-D.* ; Solimena, M.*

Impaired insulin turnover in islets from type 2 diabetic patients.

Islets 2, 30-36 (2010)
DOI Verlagsversion bestellen
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 1938-2014
e-ISSN 1938-2022
Zeitschrift Islets
Quellenangaben Band: 2, Heft: 1, Seiten: 30-36 Artikelnummer: , Supplement: ,
Verlag Landes Bioscience
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)