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Yang

Yang de Marinis

Associate professor

Yang

Role of osteopontin and its regulation in pancreatic islet

Author

  • Mengyin Cai
  • Pradeep Bompada
  • Albert Salehi
  • Juan R. Acosta
  • Rashmi B. Prasad
  • David Atac
  • Markku Laakso
  • Leif Groop
  • Yang De Marinis

Summary, in English

Osteopontin (OPN) is involved in various physiological processes and also implicated in multiple pathological states. It has been suggested that OPN may have a role in type 2 diabetes (T2D) by protecting pancreatic islets and interaction with incretins. However, the regulation and function of OPN in islets, especially in humans, remains largely unexplored. In this study, we performed our investigations on both diabetic mouse model SUR1-E1506K+/+ and islets from human donors. We demonstrated that OPN protein, secretion and gene expression was elevated in the diabetic SUR1-E1506K+/+ islets. We also showed that high glucose and incretins simultaneously stimulated islet OPN secretion. In islets from human cadaver donors, OPN gene expression was elevated in diabetic islets, and externally added OPN significantly increased glucose-stimulated insulin secretion (GSIS) from diabetic but not normal glycemic donors. The increase in GSIS by OPN in diabetic human islets was Ca2+ dependent, which was abolished by Ca2+-channel inhibitor isradipine. Furthermore, we also confirmed that OPN promoted cell metabolic activity when challenged by high glucose. These observations provided evidence on the protective role of OPN in pancreatic islets under diabetic condition, and may point to novel therapeutic targets for islet protection in T2D.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Islet cell physiology
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2018

Language

English

Pages

1426-1431

Publication/Series

Biochemical and Biophysical Research Communications

Volume

495

Issue

1

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Keywords

  • Diabetes
  • Hyperglycemia
  • Incretins
  • Insulin
  • Islets
  • Osteopontin

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Islet cell physiology

ISBN/ISSN/Other

  • ISSN: 0006-291X