Role of osteopontin and its regulation in pancreatic islet

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Sun Yat-sen University
  • Skåne University Hospital
  • University of Eastern Finland
  • University of Helsinki
  • Lund University
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Endokrinologi och diabetes

Nyckelord

Originalspråkengelska
Sidor (från-till)1426-1431
TidskriftBiochemical and Biophysical Research Communications
Volym495
Utgivningsnummer1
Tidigt onlinedatum2017 nov 24
StatusPublished - 2018
PublikationskategoriForskning
Peer review utfördJa