Pancreatic and duodenal homeobox-1 (PDX1) contributes to β-cell mass expansion and proliferation induced by Akt/PKB pathway

Mark Anthony Jara, Joao Pedro Werneck-De-Castro, Camila Lubaczeuski, James D. Johnson, Ernesto Bernal-Mizrachi

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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+/-). 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+/- mice are hyperglycemic and intolerant to glucose. The changes in glucose homeostasis in β-caAkt/pdx1+/- 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+/- 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+/- and β-caAkt mice. In conclusion, PDX1 contributes to β-cell mass expansion and glucose metabolism induced by activation of Akt signaling.

Original languageEnglish (US)
Pages (from-to)32-40
Number of pages9
Issue number2
StatePublished - Mar 3 2020
Externally publishedYes


  • AKT/PKB signaling
  • PDX1
  • diabetes
  • β-cell expansion
  • β-cell proliferation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint Dive into the research topics of 'Pancreatic and duodenal homeobox-1 (PDX1) contributes to β-cell mass expansion and proliferation induced by Akt/PKB pathway'. Together they form a unique fingerprint.

Cite this