PINK1 DEFICIENCY-MEDIATED GLUT4 UP REGULATION IN DRUG-INDUCED TYPE 2 DIABETES

Abstract

Glucose is the primary energy substrate for cellular metabolism; however, its entry into cells is strictly regulated and requires coordinated action of glucose transporters and intracellular signaling proteins. Impairment of glucose uptake is a hallmark of type 2 diabetes mellitus (T2DM), where dysregulation of insulin signaling and GLUT4-mediated glucose transport plays a central role. Cellular signaling pathways are tightly controlled by both activators and repressors, and removal of inhibitory regulators may enhance pathway efficiency.

PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine kinase, is ubiquitously expressed with high abundance in metabolically active tissues such as skeletal muscle, heart, and testes. Although PINK1 is well characterized for its role in mitochondrial quality control, its contribution to glucose metabolism remains poorly understood.

In the present study, we investigated the molecular and behavioral consequences of Pink1 gene deletion using Pink1 knockout mice. Our findings demonstrate a significant upregulation of GLUT4 expression in the absence of PINK1, suggesting that PINK1 negatively regulates GLUT4-associated glucose uptake. These results identify a previously unrecognized link between PINK1 and glucose transport regulation. However, the precise molecular mechanism underlying this regulation remains to be elucidated.

Collectively, our study highlights PINK1 as a potential modulator of glucose homeostasis and suggests that targeting PINK1-associated signaling pathways may offer new therapeutic avenues for the management of insulin resistance and type 2 diabetes.