l-norleucine on high glucose-induced insulin sensitivity and mitochondrial function in skeletal muscle cells

Biochem Biophys Res Commun. 2024 Apr 23:705:149742. doi: 10.1016/j.bbrc.2024.149742. Epub 2024 Feb 29.

Abstract

l-norleucine, an isomer of leucine, stimulates the anabolic process of insulin. However, it is not known if and how it improves insulin sensitivity and insulin resistance. This experiment describes the generation of an insulin resistance model using high glucose-induced cells and the administration of 1.0 mmol/L l-norleucine for 48 h, to observe the effects on metabolism and gene expression in skeletal muscle cells. The results showed that l-norleucine significantly increased mitochondrial ATP content, decreased the amount of reactive oxygen species (ROS) and promoted the expression of mitochondrial generation-related genes TFAM, AMPK, PGC-1α in cells under high glucose treatment; at the same time, l-norleucine also increased glucose uptake, suggesting that l-norleucine increased insulin sensitivity and improved insulin resistance. This study suggesting that l-norleucine improves insulin resistance by ameliorating oxidative stress damage of mitochondria, improving mitochondrial function, and improving insulin sensitivity in skeletal muscle cell caused by high glucose, rather than by altering mitochondrial efficiency.

Keywords: Glucose uptake; Insulin resistance; Mitochondrial function; ROS; l-norleucine.

MeSH terms

  • Glucose / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin Resistance* / physiology
  • Mitochondria / metabolism
  • Mitochondria, Muscle / metabolism
  • Muscle, Skeletal / metabolism
  • Norleucine / metabolism
  • Norleucine / pharmacology
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism

Substances

  • Insulin
  • Norleucine
  • Glucose
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha