Amino Acid-Induced Impairment of Insulin Signaling and Involvement of G-Protein Coupling Receptor

Nutrients. 2021 Jun 29;13(7):2229. doi: 10.3390/nu13072229.

Abstract

Amino acids are needed for general bodily function and well-being. Despite their importance, augmentation in their serum concentration is closely related to metabolic disorder, insulin resistance (IR), or worse, diabetes mellitus. Essential amino acids such as the branched-chain amino acids (BCAAs) have been heavily studied as a plausible biomarker or even a cause of IR. Although there is a long list of benefits, in subjects with abnormal amino acids profiles, some amino acids are correlated with a higher risk of IR. Metabolic dysfunction, upregulation of the mammalian target of the rapamycin (mTOR) pathway, the gut microbiome, 3-hydroxyisobutyrate, inflammation, and the collusion of G-protein coupled receptors (GPCRs) are among the indicators and causes of metabolic disorders generating from amino acids that contribute to IR and the onset of type 2 diabetes mellitus (T2DM). This review summarizes the current understanding of the true involvement of amino acids with IR. Additionally, the involvement of GPCRs in IR will be further discussed in this review.

Keywords: G-protein coupled receptor (GPCRs); branched-chain amino acid (BCAAs); gut microbiome; inflammation; insulin resistance (IR); mammalian target of rapamycin (mTOR); metabolic dysfunction; type 2 diabetes mellitus (T2DM).

Publication types

  • Review

MeSH terms

  • Amino Acids / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Gastrointestinal Microbiome
  • Humans
  • Insulin Resistance / physiology*
  • Metabolic Diseases / blood
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases / metabolism*
  • Up-Regulation

Substances

  • Amino Acids
  • Receptors, G-Protein-Coupled
  • MTOR protein, human
  • TOR Serine-Threonine Kinases