Protective effects of acarbose against insulitis in multiple low-dose streptozotocin-induced diabetic mice

Life Sci. 2020 Dec 15:263:118490. doi: 10.1016/j.lfs.2020.118490. Epub 2020 Sep 23.

Abstract

Aims: The development of type 1 diabetes is associated with inflammatory lesion of the pancreatic islets, known as insulitis. In this study, we focused on the protective effects of acarbose against insulitis in streptozotocin (STZ)-induced diabetic mice and the underlying mechanisms.

Main methods: The mouse models were established via intraperitoneal injection of multiple low-dose STZ. Blood glucose level and body weight were measured. The severity of insulitis and inflammatory parameters in pancreatic tissues were evaluated. Insulin levels in pancreas and serum were also assessed. In vitro, MIN6 β cells were exposed to pro-inflammatory cytokines to assess the protective effects of acarbose. Cell function and apoptosis were evaluated.

Key findings: We found that acarbose administration by gavage reduced the severity of insulitis and improved insulin levels in the experimental diabetic mice. ELISA revealed decreased levels of the inflammatory response markers IL-1β and TNF-α in mouse pancreatic tissues following acarbose treatment. In vitro, acarbose increased cell viability, decreased cell apoptosis, and improved GSIS in MIN6 β cells exposed to pro-inflammatory cytokines. In addition, caspase-3 level and p-p53/p53 ratio in β cells were reduced by acarbose treatment.

Significance: Taken together, these results revealed a novel function of acarbose in attenuating insulitis. The protective effects of acarbose elicited in vitro and in vivo were shown to be mediated, at least in part, through its anti-inflammatory action.

Keywords: Acarbose; Anti-inflammation; Diabetes mellitus; Insulitis; Pancreatic islets; Streptozotocin.

MeSH terms

  • Acarbose / pharmacology*
  • Animals
  • Diabetes Mellitus, Experimental / physiopathology*
  • Dose-Response Relationship, Drug
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protective Agents / pharmacology*

Substances

  • Glycoside Hydrolase Inhibitors
  • Protective Agents
  • Acarbose