Characteristic of GLP-1 effects on glucose metabolism in human skeletal muscle from obese patients

Regul Pept. 2011 Jun 7;168(1-3):39-44. doi: 10.1016/j.regpep.2011.03.002. Epub 2011 Mar 16.


Direct effects of GLP-1, kinase-mediated, on glucose and lipid metabolism in rat and human extrapancreatic tissues, are amply documented and also changes in type-2 diabetic (T2D) patients. Here, we explored the characteristics of the GLP-1 action and those of its analogs Ex-4 and Ex-9, on muscle glucose transport (GT) and metabolism in human morbid obesity (OB), as compared with normal and T2D subjects. In primary cultured myocytes from OB, GT and glycogen synthase a (GSa) activity values were lower than normal, and comparable to those reported in T2D patients; GT was increased by either GLP-1 or Ex-9 in a more efficient manner than in normal or T2D, up to normal levels; the Ex-4 increasing effect on GSa activity was two times that in normal cells, while Ex-9 failed to modify the enzyme activity. In OB, the control value of all kinases analyzed - PI3K, PKB, MAPKs, and p70s6K - although lower than that in normal or T2D subjects, the cells maintained their response capability to GLP-1, Ex-4, Ex-9 and insulin, with some exceptions. GLP-1 and exendins showed a direct normalizing action in the altered glucose uptake and metabolism in the muscle of obese subjects, which in the case of GLP-1 could account, at least in part, for the reported restoration of the metabolic conditions of these patients after restrictive surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged, 80 and over
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / surgery
  • Female
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glucose / metabolism*
  • Glucose / pharmacokinetics
  • Humans
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism*
  • Obesity, Morbid / metabolism*
  • Obesity, Morbid / pathology
  • Obesity, Morbid / surgery
  • Peptide Fragments / pharmacology*


  • Peptide Fragments
  • glucagon-like peptide 1 (7-36)amide
  • Glucagon-Like Peptide 1
  • Glucose