Effect of GLP-1 on glucose transport and its cell signalling in human myocytes

Regul Pept. 2005 Mar 30;126(3):203-11. doi: 10.1016/j.regpep.2004.10.002.

Abstract

Glucagon-like peptide-1 (GLP-1) controls glucose metabolism in extrapancreatic tissues participating in glucose homeostasis, through receptors not associated to cAMP. In rat hepatocytes, activation of PI3K/PKB, PKC and PP-1 mediates the GLP-1-induced stimulation of glycogen synthase. We have investigated the effect of GLP-1 in normal human myocytes, and that of its structurally related peptides exendin-4 (Ex-4) and its truncated form 9-39 (Ex-9) upon glucose uptake, and the participation of cellular enzymes proposed to mediate insulin actions. GLP-1 and both exendins activated, like insulin, PI3K/PKB and p42/44 MAPK enzymes, but p70s6k was activated only by GLP-1 and insulin. GLP-1, Ex-4 and Ex-9, like insulin, stimulated glucose uptake; wortmannin blocked the action of GLP-1, insulin and Ex-9, and reduced that of Ex-4; PD98059 abolished the effect of all peptides/hormones, while rapamycin blocked that of insulin and partially prevented that of GLP-1. H-7 abolished the action of GLP-1, insulin and Ex-4, while Ro 31-8220 prevented only the Ex-4 and Ex-9 effect. In conclusion, GLP-1, like insulin, stimulates glucose uptake, and this involves activation of PI3K/PKB, p44/42 MAPKs, partially p70s6k, and possibly PKC; Ex-4 and Ex-9 both have GLP-1-like effect upon glucose transport, in which both share with GLP-1 an activation of PI3K/PKB--partially in the case of Ex-4--and p44/42 MAPKs but not p70s6k.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Aged
  • Aged, 80 and over
  • Androstadienes / pharmacology
  • Biological Transport / drug effects
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Exenatide
  • Female
  • Flavonoids / pharmacology
  • Glucagon / pharmacology*
  • Glucagon / physiology*
  • Glucagon-Like Peptide 1
  • Glucose / metabolism*
  • Humans
  • Indoles / pharmacology
  • Insulin / pharmacology
  • Male
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Muscle Cells / drug effects
  • Muscle Cells / metabolism*
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / physiology*
  • Peptides / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase C / antagonists & inhibitors
  • Protein Precursors / pharmacology*
  • Protein Precursors / physiology*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa / antagonists & inhibitors
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction*
  • Sirolimus / pharmacology
  • Venoms / pharmacology
  • Wortmannin

Substances

  • Androstadienes
  • Flavonoids
  • Indoles
  • Insulin
  • Peptide Fragments
  • Peptides
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Precursors
  • Proto-Oncogene Proteins
  • Venoms
  • exendin (9-39)
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Glucagon-Like Peptide 1
  • Glucagon
  • Exenatide
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Protein Kinase C
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Glucose
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Sirolimus
  • Ro 31-8220
  • Wortmannin