Antidiabetic effect of free amino acids supplementation in human visceral adipocytes through adiponectin-dependent mechanism

Indian J Med Res. 2019 Jan;149(1):41-46. doi: 10.4103/ijmr.IJMR_1782_16.

Abstract

Background & objectives: : Amino acids are general nutrients having anti-diabetic property. The present study was undertaken to investigate the mechanism of anti-diabetic effects of amino acids in human visceral adipocyte cells in high glucose environment.

Methods: : Experiments were carried out in human visceral adipocytes. Adiponectin (APN) siRNAs were designed using Ambion tools. APN mRNA expression was quantified using real-time polymerase chain reaction, and protein level was studied using ELISA. AMP-activated kinase (AMPK) activity was measured and glucose uptake by 2-deoxyglucose uptake method.

Results: : Amino acids (proline and phenylalanine) exposure to adipocytes significantly (P <0.01) increased APN mRNA by 1.5-folds when compared to control whereas proline increased APN secretion by 10.6-folds (P <0.01), phenylalanine by 12.7-folds (P <0.001) and alanine by 6.3-folds (P <0.01). Free amino acid-induced AMPK activity and glucose uptake were decreased with the transient knockdown of APN.

Interpretation & conclusions: : Antidiabetic effect of the tested amino acids was exhibited by increased glucose uptake through the AMPK pathway by an APN-dependent mechanism in human visceral adipocytes. This should be tested and confirmed in in vivo system. Newer treatment modalities with amino acids which can enhance glucose uptake and APN secretion can be developed as drug for treating both diabetes and obesity.

Keywords: AMPK activity; Adiponectin; adiponectin siRNA; amino acids; anti-diabetic; glucose uptake.

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adiponectin / genetics*
  • Amino Acids / pharmacology
  • Cells, Cultured
  • Diabetes Mellitus / diet therapy*
  • Diabetes Mellitus / metabolism
  • Dietary Supplements
  • Gene Expression Regulation / drug effects
  • Glucose / metabolism*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Intra-Abdominal Fat / drug effects
  • Intra-Abdominal Fat / metabolism
  • Obesity / diet therapy*
  • Obesity / metabolism
  • Obesity / pathology
  • Phenylalanine / pharmacology
  • Proline / pharmacology
  • Protein Kinases / genetics*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Signal Transduction / drug effects

Substances

  • ADIPOQ protein, human
  • Adiponectin
  • Amino Acids
  • Hypoglycemic Agents
  • RNA, Messenger
  • RNA, Small Interfering
  • Phenylalanine
  • Proline
  • Protein Kinases
  • AMP-Activated Protein Kinase Kinases
  • Glucose