Download PDF
Horm Metab Res 2001; 33(2): 73-77
DOI: 10.1055/s-2001-12428
Original Basic

© Georg Thieme Verlag Stuttgart · New York

Effect of GLP-1 on Lipid Metabolism in Human Adipocytes

M. L. Villanueva-Peñacarrillo, L. Márquez, N. González, M. Díaz-Miguel*, I. Valverde
  • 1 Department of Metabolism, Nutrition and Hormones
  • 2 Department of General Surgery, Fundación Jiménez Díaz, Madrid, Spain
Further Information

Publication History

Publication Date:
31 December 2001 (online)

Also available at
    Permissions and Reprints

We have studied the effect of several doses of GLP-1, compared to that of insulin and glucagons, on lipogenesis, lipolysis and cAMP cellular content, in human adipocytes isolated from normal subjects. In human adipocytes, GLP-1 exerts a dual action, depending upon the dose, on lipid metabolism, being lipogenic at low concentrations of the peptide (ED50, 10-12 M), and lipolytic only at doses 10 - 100 times higher (ED50, 10-10 M); both effects are time- and GLP-1 concentration-dependent. The GLP-1 lipogenic effect is equal in magnitude to that of equimolar amounts of insulin; both hormones apparently act synergically, and their respective action is abolished by glucagon. The lipolytic effect of GLP-1 is comparable to that of glucagon, apparently additive to it, and the stimulated value induced by either one is neutralized by the presence of insulin. In the absence of IBMX, GLP-1, at 10-13 and 10-12 M, only lipogenic doses, does not modify the cellular content of cAMP, while from 10-11 M to 10-9 M, also lipolytic concentrations, it has an increasing effect; in the presence of IBMX, GLP-1 at already 10-12 M increased the cellular cAMP content. In human adipocytes, GLP-1 shows glucagon- and also insulin-like effects on lipid metabolism, suggesting the possibility of GLP-1 activating two distinct receptors, one of them similar or equal to the pancreatic one, accounting cAMP as a second messenger only for the lipolytic action of the peptide.

Key words:

Human Fat - GLP-1 (7 - 36)amide - Lipogenesis - Lipolysis - cAMP

References

  • 1 Gutniak M, Ørskov C, Holst J J, Ahren B, Effendic S. Antidiabetogenic effects of glucagon-like peptide-1(7 - 36)amide in normal subjects and patients with diabetes mellitus.  N Engl J Med. 1992;  326 1316-1322
    CrossrefPubMedSearch in Google Scholar
  • 2 D’Alessio D A, Kahn S E, Leusner C R, Ensinck J V. Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal.  J Clin Invest. 1994;  93 2263-2266
    PubMedSearch in Google Scholar
  • 3 Valverde I, Morales M, Clemente F, López-Delgado M I, Delgado E, Perea A, Villanueva-Peñacarrillo M L. Glucagon-like peptide 1: a potent glycogenic hormone.  FEBS Lett. 1994;  349 313-316
    CrossrefPubMedSearch in Google Scholar
  • 4 Villanueva-Peñacarrillo M L, Alcántara A I, Clemente F, Delgado E, Valverde I. Potent glycogenic effect of GLP-1(7 - 36)amide in rat skeletal muscle.  Diabetologia. 1994;  37 1163-1166
    PubMedSearch in Google Scholar
  • 5 Morales M, López-Delgado M I, Alcántara A, Luque M A, Clemente F, Márquez L, Puente J, Viñambres C, Malaisse W J, Villanueva-Peñacarrillo M L, Valverde I. Preserved effects upon glycogen synthase activity and glucose metabolism in isolated hepatocytes and skeletal muscle from diabetic rats.  Diabetes. 1997;  46 1264-1269
    PubMedSearch in Google Scholar
  • 6 Villanueva-Peñacarrillo M L, Delgado E, Trapote M A, Alcántara A, Clemente F, Luque M A, Perea A, Valverde I. Glucagon-like peptide-1 binding to rat hepatic membranes.  J Endocrinol. 1995;  146 183-189
    PubMedSearch in Google Scholar
  • 7 Delgado E, Luque M A, Alcántara A, Trapote M A, Clemente F, Galera C, Valverde I, Villanueva-Peñacarrillo M L. Glucagon-like peptide-1 binding to rat skeletal muscle.  Peptides. 1995;  16 225-229
    CrossrefPubMedSearch in Google Scholar
  • 8 Yang H, Egan J M, Wang Y, Moyes C D, Roth J, Montrose M H, Montrose-Rafizadeh C. GLP-1 action in L6 myotubes is via a receptor different from the pancreatic GLP-1 receptor.  Am J Physiol. 1998;  275 C675-C683
    PubMedSearch in Google Scholar
  • 9 Márquez L, Trapote M A, Luque M A, Valverde I, Villanueva-Peñacarrillo M L. Inositolphosphoglycans possibly mediate the effects of glucagon-like peptide-1(7 - 36)amide on rat liver and adipose tissue.  Cell Biochem Funct. 1998;  16 51-56
    CrossrefPubMedSearch in Google Scholar
  • 10 Trapote M A, Clemente F, Galera C, Morales M, Alcántara A I, López-Delgado M I, Villanueva-Peñacarrillo M L, Valverde I. Inositolphosphoglycans are possible mediators of the glucagon-like peptide-1(7 - 36)amide action in the liver.  J Endocrinol Invest. 1996;  19 114-118
    PubMedSearch in Google Scholar
  • 11 Galera C, Clemente F, Alcántara A, Trapote M A, Perea A, López-Delgado M I, Villanueva-Peñacarrillo M L, Valverde I. Inositolphosphoglycans and diacylglycerol are possible mediatiors in the glycogenic effect of GLP-1(7 - 36)amide in BC3H-1 myocytes.  Cell Biochem Funct. 1996;  14 43-48
    PubMedSearch in Google Scholar
  • 12 Thorens B. Expression cloning of the pancreatic B cell receptor for the gluco-incretin hormone glucagon-like peptide 1.  Proc Natl Acad Sci USA. 1992;  89 8641-8645
    CrossrefPubMedSearch in Google Scholar
  • 13 Valverde I, Mérida E, Delgado E, Trapote M A, Villanueva-Peñacarrillo M L. Presence and characterization of glucagon-like peptide-1(7 - 36)amide receptors in solubilized membranes of rat adipose tissue.  Endocrinology. 1993;  132 75-79
    CrossrefPubMedSearch in Google Scholar
  • 14 Perea A, Viñambres C, Clemente F, Villanueva-Peñacarrillo M L, Valverde I. GLP-1(7 - 36)amide effects on glucose transport and metabolism in rat adipose tissue.  Horm Metab Res. 1997;  29 417-421
    PubMedSearch in Google Scholar
  • 15 Ruiz-Grande C, Alarcón C, Mérida E, Valverde I. Lipolytic action of glucagon-like peptides in isolated rat adipocytes.  Peptides. 1992;  13 13-16
    CrossrefPubMedSearch in Google Scholar
  • 16 Mérida E, Delgado E, Molina L M, Villanueva-Peñacarrillo M L, Valverde I. Presence of glucagon and glucagon-like peptide-1-(7 - 36)amide receptors in solubilized membranes of human adipose tissue.  J Clin Endocrinol Metab. 1993;  77 1654-1657
    CrossrefPubMedSearch in Google Scholar
  • 17 Robdell M. Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis.  J Biol Chem. 1964;  239 375-380
    PubMedSearch in Google Scholar
  • 18 Greenwood F C, Hunter W H, Glover J S. The preparation of iodine-131 labelled human growth hormone of high specific activity.  Biochem J. 1963;  89 114-123
    PubMedSearch in Google Scholar
  • 19 Moody A J, Stan M A, Stan M. A simple free fat cell bioassay for insulin.  Horm Metab Res. 1974;  6 12-16
    PubMedSearch in Google Scholar
  • 20 Wieland O. Glycerol. In: Bergmeyer HU (ed.). Methods in Enzymatic Analysis.  New York; Academic Press 1963: 211-214
    Search in Google Scholar
  • 21 Perea A, Clemente F, Martinell J, Villanueva-Peñacarrillo M L, Valverde I. Physiological effect of glucagon in human isolated adipocytes.  Horm Metab Res. 1995;  27 372-375
    PubMedSearch in Google Scholar
  • 22 Oben J, Morgan L, Fletcher J, Marks V. Effect of the entero-pancreatic hormones, gastric inhibitory polypeptide and glucagon-like polypeptide-1(7 - 36) amide, on fatty acid synthesis in explants of rat adipose tissue.  J Endocrinol. 1991;  130 267-272
    PubMedSearch in Google Scholar
  • 23 Miki H, Namba M, Nishimura T, Mineo I, Matsumura T, Miyagawa J, Nakajima H, Kuwajima M, Hanafusa T, Matsuzawa Y. Glucagon-like peptide-1(7 - 36)amide enhances insulin-stimulated glucose uptake and decreases intracellular cAMP content in isolated rat adipocytes.  Biochem Biophys Acta. 1996;  1312 132-136
    PubMedSearch in Google Scholar
  • 24 Montrose-Refizadeh C, Yang H, Wang Y, Roth J, Montrose M H, Adams L G. Novel signal transduction and peptide specificity of glucagon-like peptide receptor in 3T3-L1 adipocytes.  J Cell Physiol. 1997;  172 275-283
    CrossrefPubMedSearch in Google Scholar
  • 25 Yang H, Egan J M, Wang Y, Moyes C D, Roth J, Montrose M H, Montrose-Rafizadeh C. GLP-1 action in L6 myotubes is via a receptor different from the pancreatic GLP-1 receptor.  Am J Physiol. 1998;  275 C675-C683
    PubMedSearch in Google Scholar

Dr. M. L. Villanueva-Peñacarrillo

Dpt. Metabolismo, Nutrición y Hormonas
Fundación Jiménez Díaz

Avda. Reyes Católicos, 2
28040 Madrid
Spain


Phone: Phone:+ 34 (91) 5504899

Fax: Fax:+ 34 (91) 5440247

Email: E-mail:mlvillanueva@fjd.es