Metformin and Systemic Metabolism

Research output: Contribution to journalReview articlepeer-review

Abstract

Metformin can improve patients’ hyperglycemia through significant suppression of hepatic glucose production. However, up to 300 times higher concentrations of metformin accumulate in the intestine than in the circulation, where it alters nutrient metabolism in intestinal epithelial cells and microbiome, leading to increased lactate production. Hepatocytes use lactate to make glucose at the cost of energy expenditure, creating a futile intestine–liver cycle. Furthermore, metformin reduces blood lipopolysaccharides and its initiated low-grade inflammation and increased oxidative phosphorylation in liver and adipose tissues. These metformin effects result in the improvement of insulin sensitivity and glucose utilization in extrahepatic tissues. In this review, I discuss the current understanding of the impact of metformin on systemic metabolism and its molecular mechanisms of action in various tissues.

Original languageEnglish (US)
Pages (from-to)868-881
Number of pages14
JournalTrends in Pharmacological Sciences
Volume41
Issue number11
DOIs
StatePublished - Nov 2020

Keywords

  • Metformin
  • insulin resistance
  • mitochondria
  • nutrient metabolism

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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