Regulation of fatty-acid metabolism by pancreatic hormones in cultured human hepatocytes.
The effects of pancreatic hormones and cyclic AMP on long-chain fatty-acid metabolism were investigated in human hepatocytes isolated from 12 liver biopsy specimens and cultured for 4 days in an insulin-free medium. Glucagon (10(-6) mol/L) increased endogenous ketone body production by 150%. This resulted from alterations in the partition of long-chain fatty acids from esterification toward oxidation. Glucagon or cyclic AMP enhanced (14C) oleate oxidation (basal = 45.8% +/- 5.0%; glucagon = 66.8% +/- 5.3%; cyclic AMP = 67.6% +/- 5.0% of metabolized oleate) at the expense of oleate esterification. Insulin (10(-7) mol/L) antagonized the glucagon-induced oleate oxidation. After 24 hr in basal culture conditions, the rate of lipogenesis decreased to the same low rate as in glucagon-treated cells. The presence of insulin did not restore a high rate of lipogenesis. These results are the first direct evidence of a control of ketone body production by glucagon in the human liver.
Vons
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Groupe de Recherche sur la Chirurgie du Foie et de l'Hypertension Portale, Hôpital Antoine Béclère, Clamart, France.
Pegorier
J P
JP
Girard
J
J
Kohl
C
C
Ivanov
M A
MA
Franco
D
D
D000328:Adult; D001706:Biopsy; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007657:Ketone Bodies / Q000096:biosynthesis; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010187:Pancreatic Hormones / Q000502:physiology*; D013997:Time Factors
D005227:Fatty Acids; D007328:Insulin; D007657:Ketone Bodies; D008055:Lipids; D009829:Oleic Acids; D010187:Pancreatic Hormones; D019301:Oleic Acid; D005934:Glucagon; D000242:Cyclic AMP