Affiliation:
1. Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
2. Department of Physiology, Faculty of Basics Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
Abstract
Background:
Islet β-cell dedifferentiation may be the main cause of reduced insulin secretion.
Angiotensin-(1-7) [Ang-(1-7)] can attenuate high glucose-induced apoptosis and dedifferentiation
of pancreatic β-cell, but the specific signal transduction pathway and mechanism are not
yet clear.
Objective:
This study aimed to investigate the effects of Ang-(1-7) on high glucose-induced islet
β-cell dedifferentiation by activating the phosphatidylinositol-3-kinase/Protein kinase B/ Forkhead
box transcription factor O1 (PI3K/Akt/FoxO1) signaling pathway.
Methods:
The mouse islet β-cell line MIN6 cells were passaged and cultured and randomly divided
into five groups: control (Con) group, high glucose (HG) group, HG with Ang-(1-7) group, HG
with Ang-(1-7) and specific MasR antagonist A-779 group, and HG with Ang-(1-7) and PI3K inhibitor
LY294002 group. After 48 hours, glucose-stimulated insulin secretion (GSIS) was detected
by Enzyme-Linked Immunosorbent Assay (ELISA). The mRNA and protein expression levels
of β-cell-specific factors (Pancreatic duodenal homeobox-1 (Pdx1), v-maf musculoaponeurotic fibrosarcoma
oncogene homolog A(MafA)) and endocrine progenitor cell-specific factors (Octamer
binding transcription factor 4(Oct4), Nanog) were measured by Real Time-PCR and Western blot.
The factors of protein expression levels of PI3K/Akt/FoxO1 signaling pathway (Akt, p-Akt, Fox-
O1, p-FoxO1) were determined by Western blot.
Results:
We observed for the first time that high glucotoxicity can induce dedifferentiation of pancreatic
islet β-cell, causing a decrease in insulin secretion levels and expression of Pdx1, MafA, p--
FoxO1, and p-Akt and an increase in expression of Oct4 and Nanog. After Ang-(1-7) intervention,
insulin secretion levels and expression of Pdx1, MafA, p-FoxO1 and p-Akt were increased, and
the levels of Oct4 and Nanog were reduced. However, A-779 and LY294002 could reverse this effect.
During these processes, the total Akt and total FoxO1 expression did not change significantly.
Conclusion:
Ang-(1-7) may prevent high glucose-induced pathological dedifferentiation of pancreatic
β-cell by activating the PI3K/Akt/FoxO1 signaling pathway.
Funder
Shanxi Province Science and Technology Cooperation and Exchanges Project
Research Project Supported by the Shanxi Scholarship Council of China
Scientific Research Project of Shanxi Province Health Commission of China
Publisher
Bentham Science Publishers Ltd.
Subject
Biochemistry,General Medicine,Structural Biology