Activation of central galanin receptor 2 mitigated insulin resistance in adipocytes of diabetic rats

J Endocrinol Invest. 2021 Mar;44(3):515-522. doi: 10.1007/s40618-020-01336-z. Epub 2020 Jun 25.

Abstract

Purpose: Our and other's studies showed that administration of neuropeptide galanin may mitigate insulin resistance via promoting glucose transporter 4 (GLUT4) expression and translocation in rats. The objective of this study is to investigate whether galanin receptor 2 (GAL2-R) in brain mediates the ameliorative effect of galanin on insulin resistance in adipose tissues of type 2 diabetic rats.

Methods: In this study galanin, GAL2-R agonist M1145 and GAL2-R antagonist M871 were respectively or cooperatively injected into intracerebroventricles of type 2 diabetic rats once a day for successive fifteen days. Then the plasma and fat tissues of rats were used to estimate the alterations of insulin resistance indexes.

Results: The central administration of galanin enhanced 2-deoxy-[3H]-D-glucose, peroxisome proliferator-activated receptor γ and adiponectin levels, food intake and body weight, GLUT4 mRNA expression and GLUT4 concentration in plasma membranes, as well as homeostasis model assessment-insulin resistance index. Those effects of galanin may be blocked by M817, and imitated by M1145 except for food intake and body weight.

Conclusion: Those results suggest that central GAL2-R mediates the beneficial effects of galanin on insulin sensitivity in type 2 diabetic rats. GAL2-R agonist may be taken as a potential antidiabetic agent to treat insulin resistance and type 2 diabetes.

Keywords: 2DG; Adiponectin; GLUT4; HOMA index; PPARγ.

MeSH terms

  • Adipocytes / drug effects*
  • Animals
  • Blood Glucose / analysis*
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Glucose Intolerance / metabolism
  • Glucose Intolerance / prevention & control*
  • Insulin Resistance*
  • Male
  • Rats
  • Rats, Wistar
  • Receptor, Galanin, Type 2 / agonists*

Substances

  • Blood Glucose
  • Receptor, Galanin, Type 2