New insight into the role of isorhamnetin as a regulator of insulin signaling pathway in type 2 diabetes mellitus rat model: Molecular and computational approach

Biomed Pharmacother. 2021 Mar:135:111176. doi: 10.1016/j.biopha.2020.111176. Epub 2021 Jan 2.

Abstract

We intended to examine the molecular mechanism of action of isorhamnetin (IHN) to regulate the pathway of insulin signaling. Molecular analysis, immunofluorescence, and histopathological examination were used to assess the anti-hyperglycemic and insulin resistance lowering effects of IHN in streptozotocin /high fat diet-induced type 2 diabetes using Wistar rats. At the microscopic level, treatment with IHN resulted in the restoration of myofibrils uniform arrangement and adipose tissue normal architecture. At the molecular level, treatment with IHN at three different doses showed a significant decrease in m-TOR, IGF1-R & LncRNA-RP11-773H22.4. expression and it up-regulated the expression of AKT2 mRNA, miR-1, and miR-3163 in both skeletal muscle and adipose tissue. At the protein level, IHN treated group showed a discrete spread with a moderate faint expression of m-TOR in skeletal muscles as well as adipose tissues. We concluded that IHN could be used in the in ameliorating insulin resistance associated with type 2 diabetes mellitus.

Keywords: Bioinformatics; Insulin resistance; Isorhamnetin; RNA; Type 2 diabetes mellitus.

MeSH terms

  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / enzymology
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / pathology
  • Hypoglycemic Agents / pharmacology*
  • Insulin / blood*
  • Insulin Resistance*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Myofibrils / drug effects*
  • Myofibrils / metabolism
  • Myofibrils / pathology
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quercetin / analogs & derivatives*
  • Quercetin / pharmacology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, IGF Type 1 / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Hypoglycemic Agents
  • Igf1r protein, rat
  • Insulin
  • MicroRNAs
  • RNA, Long Noncoding
  • 3-methylquercetin
  • Quercetin
  • mTOR protein, rat
  • Receptor, IGF Type 1
  • Akt2 protein, rat
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases