1. Academic Validation
  2. HL271, a novel chemical compound derived from metformin, differs from metformin in its effects on the circadian clock and metabolism

HL271, a novel chemical compound derived from metformin, differs from metformin in its effects on the circadian clock and metabolism

  • Biochem Biophys Res Commun. 2016 Jan 15;469(3):783-9. doi: 10.1016/j.bbrc.2015.11.069.
Hansang Row 1 Jaekap Jeong 2 Sehyung Cho 3 Sungwuk Kim 2 Kyungjin Kim 4
Affiliations

Affiliations

  • 1 Department of Biological Sciences, Seoul National University, Seoul 151-742, South Korea; Department of Brain and Cognitive Science, DGIST, Daegu 711-873, South Korea.
  • 2 Hanall Biopharma Inc., Seoul 138-950, South Korea.
  • 3 Research Center and Department of Physiology, Kyung Hee University School of Medicine, Seoul 130-701, South Korea.
  • 4 Department of Brain and Cognitive Science, DGIST, Daegu 711-873, South Korea. Electronic address: kyungjin@dgist.ac.kr.
Abstract

Metformin is a treatment of choice for patients with type 2 diabetes. Its action involves the phosphorylation of 5'-adenosine monophosphate activated protein kinase (AMPK), leading to inhibition of liver gluconeogenesis. The effects of a novel chemical compound derived from metformin, HL271, on molecular and physiological actions involving AMPK and rhythmically-expressed circadian clock genes were investigated. HL271 potently activated AMPK in a dose-dependent manner, and produced shortening of the circadian period and enhanced degradation of the clock genes PER2 and CRY1. Although the molecular effects of HL271 resembled those of metformin, it produced different physiological effects in mice with diet-induced obesity. HL271 did not elicit glucose-lowering or insulin-sensitizing effects, possibly because of altered regulation of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1. This indicated that, although HL271 acted on circadian clock machinery through a similar molecular mechanism to metformin, it differed in its systemic effect on glucose and lipid metabolite regulations.

Keywords

AMPK; Cell metabolism; Circadian clock; Gluconeogenesis; Lipid metabolites; Metformin.

Figures
Products