Regulation of VLDL secretion in primary culture of rat hepatocytes: involvement of cAMP and cAMP‐dependent protein kinases
- 1 February 1994
- journal article
- Published by Wiley in European Journal of Clinical Investigation
- Vol. 24 (2), 137-148
- https://doi.org/10.1111/j.1365-2362.1994.tb00979.x
Abstract
When hepatocytes were cultured for 24 h in the presence of forskolin (10(-4) mol l-1) or isobutylmethylxanthine (IBMX, 10(-3) mol l-1), the intracellular cAMP concentration peaked (320-380 pmol mg-1 protein) after 10-20 min of culture. This increase was accompanied by a decrease in the secretion of triacylglycerol, cholesterol and apoprotein B associated with VLDL. After 4 h cAMP levels had returned almost to basal values but the inhibition of VLDL secretion persisted. There was a small intracellular accumulation of triacylglycerol but not of apoprotein B. Addition of forskolin and IBMX together led to a further increase in intracellular cAMP and a further suppression of VLDL output. Similar effects on the secretion of VLDL were also observed after addition of Bt2cAMP. Exposure of cell cultures to glucagon (10(-7) mol l-1) for only 10 min raised cellular cAMP levels to > 200 pmol mg-1 protein, and suppressed VLDL secretion during the next 24 h to < 40% of control. All of the substances tested inhibited de novo synthesis of fatty acids but had little or no effect on cholesterol synthesis and did not inhibit oleate esterification to triacylglycerol. The cAMP-dependent protein kinase antagonist Rp-cAMPS prevented suppression of VLDL triacylglycerol secretion induced by glucagon (10(-7) mol l-1) and abolished glucagon-induced ketogenesis. Rp-cAMPS also inhibited Bt2cAMP (7.5 x 10(-6) mol l-1)-induced suppression of VLDL secretion and enhancement of ketogenesis. It is concluded that rat hepatic VLDL metabolism can be regulated by cAMP and cAMP-dependent protein kinases, and that the initial transient rise in cellular cAMP levels induced by glucagon is sufficient to maintain a long-term inhibitory effect on assembly and secretion of VLDL.Keywords
This publication has 39 references indexed in Scilit:
- Expression cloning and signaling properties of the rat glucagon receptorScience, 1993
- Forskolin inhibits and reverses the effects of brefeldin A on Golgi morphology by a cAMP-independent mechanism.The Journal of cell biology, 1991
- Mechanism of galanin-inhibited insulin releaseEuropean Journal of Biochemistry, 1988
- Mechanism of galanin-inhibited insulin release. Occurrence of a pertussis-toxin-sensitive inhibition of adenylate cyclaseEuropean Journal of Biochemistry, 1988
- Hormonal Regulation Of Hepatic Gluconeogenesis And GlycolysisAnnual Review of Biochemistry, 1988
- A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesisFEBS Letters, 1987
- The production and utility of monoclonal antibodies to rat apolipoprotein B lipoproteinsAtherosclerosis, 1986
- Mobilization of intracellular calcium by glucagon and cyclic AMP analogues in isolated rat hepatocytesFEBS Letters, 1986
- Effect of E-series prostaglandins on cyclic AMP-dependent and -independent hormone-stimulated glycogenolysis in hepatocytesDiabetes, 1985
- Effects of duodenal perfusion with sodium taurocholate on biliary and pancreatic secretion in manEuropean Journal of Clinical Investigation, 1982