Role of osteopontin and its regulation in pancreatic islet
(2018) In Biochemical and Biophysical Research Communications 495(1). p.1426-1431- 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... (More)
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.
(Less)
- author
- Cai, Mengyin ; Bompada, Pradeep LU ; Salehi, Albert LU ; Acosta, Juan R. ; Prasad, Rashmi B. LU ; Atac, David LU ; Laakso, Markku ; Groop, Leif LU and De Marinis, Yang LU
- organization
- publishing date
- 2018
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Diabetes, Hyperglycemia, Incretins, Insulin, Islets, Osteopontin
- in
- Biochemical and Biophysical Research Communications
- volume
- 495
- issue
- 1
- pages
- 1426 - 1431
- publisher
- Elsevier
- external identifiers
-
- scopus:85035350858
- pmid:29180017
- ISSN
- 0006-291X
- DOI
- 10.1016/j.bbrc.2017.11.147
- language
- English
- LU publication?
- yes
- id
- 136fe9a4-7fbe-4002-87a8-c8316d27b19c
- date added to LUP
- 2017-12-12 14:36:34
- date last changed
- 2024-04-15 00:09:41
@article{136fe9a4-7fbe-4002-87a8-c8316d27b19c, abstract = {{<p>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 Ca<sup>2+</sup> dependent, which was abolished by Ca<sup>2+</sup>-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.</p>}}, author = {{Cai, Mengyin and Bompada, Pradeep and Salehi, Albert and Acosta, Juan R. and Prasad, Rashmi B. and Atac, David and Laakso, Markku and Groop, Leif and De Marinis, Yang}}, issn = {{0006-291X}}, keywords = {{Diabetes; Hyperglycemia; Incretins; Insulin; Islets; Osteopontin}}, language = {{eng}}, number = {{1}}, pages = {{1426--1431}}, publisher = {{Elsevier}}, series = {{Biochemical and Biophysical Research Communications}}, title = {{Role of osteopontin and its regulation in pancreatic islet}}, url = {{http://dx.doi.org/10.1016/j.bbrc.2017.11.147}}, doi = {{10.1016/j.bbrc.2017.11.147}}, volume = {{495}}, year = {{2018}}, }