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Pancreatic and duodenal homeobox-1 (PDX1) contributes to β-cell mass expansion and proliferation induced by Akt/PKB pathway.
- Source :
-
Islets [Islets] 2020 Mar 03; Vol. 12 (2), pp. 32-40. - Publication Year :
- 2020
-
Abstract
- Maintenance of pancreatic β-cell mass and function is fundamental to glucose homeostasis and to prevent diabetes. The PI3 K-Akt-mTORC1 pathway is critical for β-cells mass and function, while PDX1 has been implicated in β-cell development, maturation, and function. Here we tested whether Akt signaling requires PDX1 expression to regulate β-cell mass, proliferation, and glucose homeostasis. In order to address that, we crossed a mouse model overexpressing constitutively active Akt mutant in β-cells ( β-caAkt ) with mice lacking one allele of PDX1gene ( β-caAkt/pdx1 <superscript>+/-</superscript> ) . While the β-caAkt mice exhibit higher plasma insulin levels, greater β-cell mass and improved glucose tolerance compared to control mice, the β-caAkt/pdx1 <superscript>+/-</superscript> mice are hyperglycemic and intolerant to glucose. The changes in glucose homeostasis in β-caAkt/pdx1 <superscript>+/-</superscript> were associated with a 60% reduction in β-cell mass compared to β-caAkt mice. The impaired β-cell mass in the β-caAkt/pdx1 <superscript>+/-</superscript> mice can be explained by a lesser β-cell proliferation measured by the number of Ki67 positive β-cells. We did not observe any differences in apoptosis between β-caAkt/pdx1 <superscript>+/-</superscript> and β-caAkt mice. In conclusion, PDX1 contributes to β-cell mass expansion and glucose metabolism induced by activation of Akt signaling.
- Subjects :
- Animals
Apoptosis
Homeostasis
Insulin metabolism
Mechanistic Target of Rapamycin Complex 1 metabolism
Mice
Models, Animal
Signal Transduction
Cell Proliferation
Glucose metabolism
Homeodomain Proteins metabolism
Insulin-Secreting Cells physiology
Proto-Oncogene Proteins c-akt metabolism
Trans-Activators metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1938-2022
- Volume :
- 12
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Islets
- Publication Type :
- Academic Journal
- Accession number :
- 32876522
- Full Text :
- https://doi.org/10.1080/19382014.2020.1762471