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Jens Lagerstedt

Associate professor

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Apolipoprotein A-I primes beta cells to increase glucose stimulated insulin secretion

Author

  • Oktawia Nilsson
  • Rita Del Giudice
  • Mototsugu Nagao
  • Caitriona Grönberg
  • Lena Eliasson
  • Jens O Lagerstedt

Summary, in English

The increase of plasma levels of high-density lipoproteins and Apolipoprotein A-I (ApoA-I), its main protein component, has been shown to have a positive action on glucose disposal in type 2 diabetic patients. The current study investigates the unexplored function of ApoA-I to prime beta cells for improved insulin secretion. INS-1E rat clonal beta cells as well as isolated murine islets were used to study the effect of ApoA-I on responsiveness of the beta cells to high glucose challenge. Confocal and transmission electron microscopy were used to dissect ApoA-I mechanisms of action. Chemical endocytosis blockers were used to understand the role of ApoA-I internalization in mediating its positive effect. Pre-incubation of beta cells and isolated murine islets with ApoA-I augmented glucose stimulated insulin secretion. This effect appeared to be due to an increased reservoir of insulin granules at the cell membrane, as confirmed by confocal and transmission electron microscopy. Moreover, ApoA-I induced pancreatic and duodenal homeobox 1 (PDX1) shuttling from the cytoplasm to the nucleus, with the subsequent increase in the proinsulin processing enzyme protein convertase 1 (PC1/3). Finally, the blockade of ApoA-I endocytosis in beta cells resulted in a loss of ApoA-I positive action on insulin secretion. The proposed mechanisms of the phenomenon here described include ApoA-I internalization into beta cells, PDX1 nuclear translocation, and increased levels of proinsulin processing enzymes. Altogether, these events lead to an increased number of insulin granules.

Department/s

  • Diabetes - Islet Cell Exocytosis
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Department of Clinical Sciences, Malmö

Publishing year

2020-03-01

Language

English

Publication/Series

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volume

1866

Issue

3

Document type

Journal article

Publisher

Elsevier

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 0925-4439