Ageing-Related Alterations in Renal Epithelial Glucose Transport

Int J Mol Sci. 2023 Nov 17;24(22):16455. doi: 10.3390/ijms242216455.

Abstract

The kidney plays a crucial role in glucose homeostasis by regulating glucose transport. We aimed to investigate the impact of alterations in glucose transport on glucose metabolism during ageing. Adult male Sprague Dawley rats were divided into five groups: 3-month, 6-month, and 12-month control groups, and 6- and 12-month groups receiving the hydrogen sulfide donor molecule GYY4137. The study found that, as age increased, daily urinary uric acid and protein levels increased in the 12-month group. Blood sugar level and HOMA-IR index increased in the 12-month group, and were partially improved by GYY4137. The kidney tissue showed mild glomerulosclerosis in the 12-month group, which was diminished by GYY4137. Gene expression analysis showed decreased sirtuin and increased p21 expression in the aging groups. Increased SGLT1 and SGLT2 expression was observed in the 12-month group, which was reversed by GYY4137. Both GLUT1 and GLUT2 expression was increased in the 6- and 12-month groups, and reversed by GYY4137 in the 12-month group. The study concluded that aging was associated with increased blood sugar levels and the HOMA-IR index, and the abundance of renal glucose transporters increased as aging progressed. GYY4137 effectively reversed aging-related alterations in glucose homeostasis and renal epithelial transporters.

Keywords: GYY4137; ageing; glucose homeostasis; glucose transporter; hydrogen sulfide.

MeSH terms

  • Aging
  • Animals
  • Blood Glucose / metabolism
  • Glucose / metabolism
  • Hydrogen Sulfide* / metabolism
  • Kidney / metabolism
  • Male
  • Organothiophosphorus Compounds* / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • GYY 4137
  • Blood Glucose
  • Organothiophosphorus Compounds
  • Glucose
  • Hydrogen Sulfide