GLP-1 effect upon the GPI/IPG system in adipocytes and hepatocytes from diabetic rats.
GLP-1 (glucagon-like peptide 1), proposed as a possible tool for Type 2 diabetes therapy, has insulin-like effects upon glucose metabolism in extrapancreatic tissues, whose plasma membranes contain specific receptors for the peptide, being those, at least in liver and muscle, not associated to the adenylate cyclase/cAMP system. GLP-1, as insulin, modulates the content of glycosylphosphatidylinositols (GPIs)--precursors of inositolphosphoglycans (IPGs), considered mediators of insulin action--in several extrapancreatic cell lines and in normal rat hepatocytes and adipocytes. In the present paper, we document that in a streptozotocin-induced Type 2 diabetic rat model, GLP-1, as insulin, provokes a rapid decrease of the [myo-3H-inositol]GPI content in isolated adipocytes--indicative of its hydrolysis and immediate short-lived generation of IPG--as that previously observed in normal animals; in hepatocytes, GLP-1, but not insulin, induced a reduction in the cellular GPI, although delayed in relation to normal rats. In adipocytes from streptozotocin-induced Type 1 diabetic rats, GLP-1, as insulin, seems to induce a reduction in the cellular GPI content, which was smaller and occurred later than that provoked in the Type 2 diabetic model; in the hepatocytes, GLP-1 and insulin failed to affect the control GPI content at any time tested. In Type 2 diabetic rat, the hepatocyte retains its response capability to GLP-1, but not to insulin, suggesting that the peptide could be bypassing possible defective steps in the insulin signaling pathway in the liver of this diabetic model.
Márquez
L
L
Department of Metabolism, Nutrition and Hormones, Fundación Jiménez Díaz, Madrid, Spain.
González
N
N
Puente
J
J
Valverde
L
L
Villanueva-Peñacarrillo
M L
ML
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D005934:Glucagon / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D007295:Inositol Phosphates; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D009844:Oligosaccharides / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D011134:Polysaccharides; D011498:Protein Precursors / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D017261:Glycosylphosphatidylinositols; D007004:Hypoglycemic Agents; D007295:Inositol Phosphates; D007328:Insulin; D009844:Oligosaccharides; D010446:Peptide Fragments; D011134:Polysaccharides; D011498:Protein Precursors; C028039:inositol phosphate glycan; D052216:Glucagon-Like Peptide 1; D005934:Glucagon