Role of osteopontin and its regulation in pancreatic islet

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
Organisations
External organisations
  • Sun Yat-sen University
  • Skåne University Hospital
  • University of Eastern Finland
  • University of Helsinki
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes

Keywords

  • Diabetes, Hyperglycemia, Incretins, Insulin, Islets, Osteopontin
Original languageEnglish
Pages (from-to)1426-1431
JournalBiochemical and Biophysical Research Communications
Volume495
Issue number1
Early online date2017 Nov 24
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes