Alkaline pH induces IRR-mediated phosphorylation of IRS-1 and actin cytoskeleton remodeling in a pancreatic beta cell line.
Biochimie
; 138: 62-69, 2017 Jul.
Article
in En
| MEDLINE
| ID: mdl-28438671
ABSTRACT
Secretion of mildly alkaline (pH 8.0-8.5) juice to intestines is one of the key functions of the pancreas. Recent reports indicate that the pancreatic duct system containing the alkaline juice may adjoin the endocrine cells of pancreatic islets. We have previously identified the insulin receptor-related receptor (IRR) that is expressed in islets as a sensor of mildly alkaline extracellular media. In this study, we show that those islet cells that are in contact with the excretory ducts are also IRR-expressing cells. We further analyzed the effects of alkaline media on pancreatic beta cell line MIN6. Activation of endogenous IRR but not of the insulin receptor was detected that could be inhibited with linsitinib. The IRR autophosphorylation correlated with pH-dependent linsitinib-sensitive activation of insulin receptor substrate 1 (IRS-1), the primary adaptor in the insulin signaling pathway. However, in contrast with insulin stimulation, no protein kinase B (Akt/PKB) phosphorylation was detected as a result of alkali treatment. We observed overexpression of several early response genes (EGR2, IER2, FOSB, EGR1 and NPAS4) upon alkali treatment of MIN6 cells but those were IRR-independent. The alkaline medium but not insulin also triggered actin cytoskeleton remodeling that was blocked by pre-incubation with linsitinib. We propose that the activation of IRR by alkali might be part of a local loop of signaling between the exocrine and endocrine parts of the pancreas where alkalinization of the juice facilitate insulin release that increases the volume of secreted juice to control its pH and bicabonate content.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Actin Cytoskeleton
/
Receptor, Insulin
/
Insulin-Secreting Cells
/
Insulin Receptor Substrate Proteins
/
Insulin
Limits:
Animals
Language:
En
Journal:
Biochimie
Year:
2017
Document type:
Article
Affiliation country:
RUSSIA