Lack of effect of calcitonin gene-related peptide and amylin on major markers of glucose metabolism in hepatocytes.
Effects of amylin and calcitonin gene-related peptide on several processes involved in carbohydrate metabolism were investigated in rat hepatocytes, non-parenchymal cells (Kupffer, Ito and endothelial cells) and alveolar macrophages. In hepatocytes, cAMP levels were increased 25-fold by glucagon (10 nM), less than 2-fold by calcitonin gene-related peptide (100 nM) and not at all by amylin (100 nM). In non-parenchymal cells and cultured alveolar macrophages, calcitonin gene-related peptide potently, and amylin weakly, stimulated cAMP levels. In hepatocytes neither amylin nor calcitonin gene-related peptide affected glycogen phosphorylase activity, glucose output, lactate uptake, glycogen synthesis, glycogen mass or tyrosine aminotransferase activity. The density of calcitonin gene-related peptide specific binding sites in parenchymal cells was 10-fold less then seen in non-parenchymal cells. We found no significant evidence of specific amylin binding sites. These results are consistent with the notion that amylin does not exert a direct effect in hepatocytes. However, we do not rule out that amylin may affect hepatic glucose output indirectly through Cori cycling of lactate derived from skeletal muscle or from interactions through non-parenchymal cells.
Pittner
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RA
Amylin Pharmaceuticals, Inc., San Diego, CA 92121-3027, USA. rpittner@amylin.com
D000682:Amyloid / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D015415:Biomarkers; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D014444:Tyrosine Transaminase / Q000096:biosynthesis
D000682:Amyloid; D015415:Biomarkers; D058228:Islet Amyloid Polypeptide; D008112:Liver Glycogen; D019344:Lactic Acid; D000242:Cyclic AMP; D006005:Phosphorylases; D014444:Tyrosine Transaminase; D005947:Glucose; D015740:Calcitonin Gene-Related Peptide