Lentivirus-Mediated hFGF21 Stable Expression in Liver of Diabetic Rats Model and Its Antidiabetic Effect Observation

Hum Gene Ther. 2020 Apr;31(7-8):472-484. doi: 10.1089/hum.2019.322. Epub 2020 Mar 30.

Abstract

The incidence of type 2 diabetes mellitus (T2DM) has been increasing annually, which is a serious threat to human health. Fibroblast growth factor 21 (FGF21) is one of the most popular targets for the treatment of diabetes because it effectively improves glycolipid metabolism. In our experiment, human FGF21 (hFGF21) was injected and stably expressed in the liver tissues of a rat T2DM model with lentivirus system. Based on clinical and histopathological examinations, islet cells were protected and liver tissue lesions were repaired for >4 months. Glucose metabolism and histopathology were controlled perfectly when hFGF21 was stably expressed in partial liver of T2DM rats. The results showed that the liver tissue cell apoptosis was reduced, the lipid droplet content was decreased, the oxidative stress indexes were improved, the glycogen content was increased, and the islet cells were increased too. Besides, insulin sensitivity and glycogen synthesis-related genes expression were increased, but cell apoptosis-related genes caspase3 and NFκB expression were decreased. The effectiveness of results suggested that injecting hFGF21 to rats liver could effectively treat T2DM.

Keywords: T2DM rats model; antidiabetes; fibroblast growth factor 21; lentivirus; stable expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / therapy*
  • Fibroblast Growth Factors / genetics*
  • Genetic Therapy / methods*
  • HEK293 Cells
  • Humans
  • Insulin / metabolism
  • Lentivirus*
  • Lipids / blood
  • Liver / metabolism*
  • Male
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Streptozocin

Substances

  • Blood Glucose
  • Insulin
  • Lipids
  • fibroblast growth factor 21
  • Streptozocin
  • Fibroblast Growth Factors