Title:Angiotensin-(1-7) Improves Islet β-cell Dedifferentiation by Activating
PI3K/Akt/FoxO1 Pathway
Volume: 30
Issue: 12
Author(s): Hao Guo, Dandan Guo, Min An, Ruonan Zhang, Caixia Wang and Junhua He*
Affiliation:
- Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
Keywords:
Diabetes mellitus, angiotensin-(1-7), islet β-cell, dedifferentiation, pi3k/akt/foxo1, protein.
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.
Objectives: 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.
