Anti-diabetic Role of Adropin in Streptozotocin Induced Diabetic Rats via Alteration of PI3K/Akt and Insulin Signaling Pathway

J Oleo Sci. 2021;70(5):657-664. doi: 10.5650/jos.ess21019.

Abstract

Diabetes mellitus (DM) is a hyperglycemia-related multifactorial condition with an elevated risk of microvascular and microvascular complications associated with this disease. The current experimental study was to examine the antidiabetic activity of streptozotocin (STZ)-induced adropin against diabetic rats by altering the PI3K/Akt and insulin signaling pathways. STZ (60 mg/kg) was used for the induction of DM and rats were divided into different groups and received the adropin (20, 40 and 80 mg/kg) and glibenclamide (10 mg/kg) till 28 days. Body weight, plasma insulin, blood glucose and food intake were estimated, respectively. Biochemical enzymes, carbohydrate enzymes, lipid parameters, AMPK and insulin signalling pathway parameters were estimated. GLUT4 and PPARγ expression were also estimated. Oral administration of adropin significantly (p < 0.001) increased the glycogen, glucose-6-phosphatase dehydrogenase, insulin, hexokinase and belittled the blood glucose level, fructose 1-6-biphosphatase, glucose-6-phosphatase at dose dependent manner. Adropin significantly (p < 0.001) reduced the level of triglyceride, cholesterol, low density lipoprotein, very low density lipoprotein and increased the level of high density lipoprotein at dose dependent manner. Adropin significantly (p < 0.001) activated the Akt, IRS-2, IRS-1, IR, p-AKT and PI3k, which are the key modulator molecules of PI3K/Akt, AMPK and insulin signalling pathway in DM rats. The current experimental study confirms the anti-diabetic effect of adropin on DM rats induced by AMPK and insulin signalling pathway against STZ.

Keywords: adropin; AMPK pathway; PI3K/Akt pathway; antioxidant; carbohydrate enzymes; free radical; insulin signalling; streptozotocin.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Blood Proteins / pharmacology*
  • Blood Proteins / physiology*
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetes Mellitus, Experimental / metabolism*
  • Dose-Response Relationship, Drug
  • Hypoglycemic Agents*
  • Insulin / metabolism*
  • Lipid Metabolism / drug effects
  • Male
  • Peptides / pharmacology*
  • Peptides / physiology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics*
  • Streptozocin

Substances

  • Blood Proteins
  • ENHO protein, rat
  • Hypoglycemic Agents
  • Insulin
  • Peptides
  • Streptozocin
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinases