Dapagliflozin elevates plasma high-density lipoprotein levels and influences visceral fat gene expression in streptozotocin-induced diabetes mellitus

J Pharm Pharmacol. 2021 Apr 27;73(6):778-784. doi: 10.1093/jpp/rgab005.

Abstract

Objectives: Dapagliflozin (Dapa) could potentially be used to treat type 1 diabetes mellitus. We tested the hypothesis that it would influence blood lipid levels and visceral fat accumulation in a rodent diabetic model.

Methods: We used three groups of male Wistar rats: Controls, streptozotocin (STZ)-treated rats and STZ-treated orally with Dapa (STZ+Dapa), 10 mg/kg/day for six weeks. Blood glucose and serum lipids levels were determined. Plasma levels of lipases (hormone-sensitive lipase, HSL and lipoprotein lipase, LPL), adipokines (leptin and adiponectin) and proinflammatory cytokines [tumour necrosis factor-alpha (TNFα) and interleukin-6 (IL-6)] were determined by ELISA assays. mRNA levels in the perirenal fat were determined by real-time PCR.

Key findings: Dapa suppressed STZ-related hyperglycemia by 20% (P < 0.05) and increased serum HDL when compared to the controls and the STZ-only treated rats (both P < 0.05). STZ treatment caused elevations of other serum lipids that were resistant to Dapa treatment. Dapa treatment also increased both plasma and visceral fat mRNA levels of leptin, LPL and IL-6, while decreasing plasma and fat expressions of HSL and TNFα compared to the STZ-only treated rats (all P < 0.05).

Conclusions: Our results suggest that Dapa, in addition to its antidiabetic effect, also influences the function of adipose tissue which could be beneficial in the treatment of diabetes.

Keywords: adipokines; cytokines; dapagliflozin; diabetes mellitus type 1; lipoproteins; rat.

MeSH terms

  • Adipose Tissue / metabolism
  • Administration, Oral
  • Animals
  • Benzhydryl Compounds / pharmacology*
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Gene Expression Regulation / drug effects
  • Glucosides / pharmacology*
  • Hypoglycemic Agents / pharmacology*
  • Intra-Abdominal Fat / drug effects
  • Lipids / blood
  • Lipoproteins, HDL / blood*
  • Male
  • Rats
  • Rats, Wistar
  • Streptozocin

Substances

  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Hypoglycemic Agents
  • Lipids
  • Lipoproteins, HDL
  • dapagliflozin
  • Streptozocin