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Research Paper

Impaired insulin turnover in islets from type 2 diabetic patients

Florian Ehehalt, Klaus Knoch, Katja Erdmann, Christian Krautz, M Jäger, A. Steffen, C. Wegbrod, Ronny Meisterfeld, Stephan Kersting, Hendrik Bergert, E. Kuhlisch, Stefan Bornstein, Ezio Bonifacio, Hans-Detlev Saeger and Michele Solimena

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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.

Authors

Florian Ehehalt

Department of GI, Thoracic and Vascular Surgery; Dresden University of Technology, Dresden, Germany

Klaus Knoch

Department of Molecular Diabetology and Paul Langerhans Institute Dresden, Dresden University of Technology, Dresden, Germany

Katja Erdmann

Department of Molecular Diabetology and Paul Langerhans Institute Dresden, Dresden University of Technology, Dresden, Germany

Christian Krautz

Department of GI, Thoracic and Vascular Surgery; Dresden University of Technology, Dresden, Germany

M Jäger

Department of Molecular Diabetology and Paul Langerhans Institute Dresden, Dresden University of Technology, Dresden, Germany

A. Steffen

Department of Medicine III and Paul Langerhans Institute Dresden Dresden University of Technology, Dresden, Germany

C. Wegbrod

Department of Molecular Diabetology and Paul Langerhans Institute Dresden, Dresden University of Technology, Dresden, Germany

Ronny Meisterfeld

Department of GI, Thoracic and Vascular Surgery; Dresden University of Technology, Dresden, Germany

Stephan Kersting

Department of GI, Thoracic and Vascular Surgery; Dresden University of Technology, Dresden, Germany

Hendrik Bergert

Department of GI, Thoracic and Vascular Surgery; Dresden University of Technology, Dresden, Germany

E. Kuhlisch

Institute for Medical Informatics and Biometrics; Dresden University of Technology, Dresden, Germany

Stefan Bornstein

Department of Medicine III and Paul Langerhans Institute Dresden Dresden University of Technology, Dresden, Germany

Ezio Bonifacio

Preclinical Approaches to Stem Cell Therapy/Diabetes, Center for Regenerative Therapies Dresden, Dresden Germany

Hans-Detlev Saeger Corresponding author: hans-detlev.saeger@uniklinikum-dresden.de

Department of GI, Thoracic and Vascular Surgery; Dresden University of Technology, Dresden, Germany

Michele Solimena Corresponding author: michele.solimena@tu-dresden.de

Preclinical Approaches to Stem Cell Therapy/Diabetes, Center for Regenerative Therapies Dresden, Dresden Germany

This is an open-access article

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