Phosphatase and Tensin Homologue (PTEN)-Induced Putative Kinase 1 Promotes Pancreatic Β-Cells Proliferation in Glucotoxicity Through Activation of Akt/Mtor/Hif-1α Pathway

Sustained high glucose is harmful to pancreatic β-cells, resulting in impaired pancreatic β-cells proliferation. Understanding the molecular mechanisms related to β-cells proliferation is pivotal for the prevention of β-cells injury caused by glucotoxicity. The role of Phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1) in the proliferation of pancreatic β-cells constantly exposed to high glucose was studied. Sustained high glucose decreased Akt/mTOR/ HIF-1α proteins expression in INS-1 β-cells, and that this reduction can be further prompted by PINK1 silencing and conversely enhanced by PINK1 overexpression. PINK1 deficiency aggravated glucotoxicity-induced pancreatic β-cells proliferation and inhibition of Akt/mTOR/HIF-1α pathway whereas PINK1 over-expression could reverse these adverse effects. This study provides fundamental data supporting the potential protective role of PINK1 as a new therapeutic target necessary to preserve β-cells proliferation under non-physiological hyperglycemia conditions.