A new hypoglycemic mechanism of catalpol revealed by enhancing MyoD/MyoG-mediated myogenesis.

Abstract

AIMS:

Enhancing myogenesis has been identified as a possible target to improve insulin sensitivity and protect against metabolic diseases. Catalpol, an iridoid glycoside, has been shown to exert a hypoglycaemic effect by improvement of insulin sensitivity; however, the underlying mechanism remains unknown. In this study, we tested whether catalpol has the potential to improve insulin sensitivity by augmenting myogenesis.

MAIN METHODS:

We examined the hypoglycaemic mechanism of catalpol in db/db mice and C2C12 cells. db/db mice were treated with catalpol (200 mg/kg) for 8 consecutive weeks. Serum analysis, skeletal muscle performance and histology, and gene and protein expression were performed. In vitro glucose uptake, gene and protein expression were determined, and small interfering RNA was used to identify the underlying hypoglycaemic mechanism of catalpol.

KEY FINDINGS:

In this study, we tested whether catalpol has the potential to improve skeletal insulin sensitivity by augmenting myogenesis, in which we found that, catalpol treatment in db/db mice lowered blood glucose and improved insulin sensitivity via activation of phosphatidylinositol‑3‑Kinase (PI3K)/protein kinase B (AKT) pathway. Moreover, catalpol-treated mice exhibited enhanced myogenesis, as evidenced by increased myogenic differentiation (MyoD), myogenin (MyoG) and myosin heavy chain (MHC) expressions. The in vitro experimental results showed that both catalpol and metformin enhanced glucose uptake via activation of PI3K/AKT pathway. However, unlike metformin, the PI3K/AKT pathway activation by catalpol was dependent on enhanced MyoD/MyoG-mediated myogenesis.

SIGNIFICANCE:

Improvement of insulin sensitivity by enhancing MyoD/MyoG-mediated myogenesis may constitute a new therapeutic approach for treating type 2 diabetes.

• Authors: Dengqiu Xu, Lu Wang, Zhenzhou Jiang, Guolin Zhao, Hozeifa M Hassan, Lixin Sun, Sisi Fan, Zhixing Zhou, Luyong Zhang, Tao Wang
• Journal: Life sciences (Life Sci) Vol. 209 Pg. 313-323 (Sep 15 2018) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 30118770 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Iridoid Glucosides
• MyoD Protein
• MyoD1 myogenic differentiation protein
• Myog protein, mouse
• Myogenin
• catalpol

Topics

• Animals
• Blood Glucose (metabolism)
• Cell Differentiation (drug effects)
• Diabetes Mellitus, Experimental (drug therapy, metabolism, pathology)
• Diabetes Mellitus, Type 2 (drug therapy, metabolism, pathology)
• Hypoglycemic Agents (pharmacology)
• Insulin Resistance
• Iridoid Glucosides (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Muscle Development (drug effects)
• Muscle, Skeletal (drug effects, physiology)
• MyoD Protein (metabolism)
• Myogenin (metabolism)