Abstract
The insulin-like effects of vanadiumin vivo are likely to be achieved at micromolar concentrations. Demonstrated effects of vanadium on adipose tissue of streptozotocin-diabetic rats include inhibition of basal and stimulated rates of lipolysis and effects on fat cell protein phosphorylation. The studies described below examined the effects of vanadium (to a maximum concentration of 0.5 mM) on adipose cells or tissuein vitro. Vanadium, added as a vanadyl-albumin complex or as sodium orthovanadate, produced a marked (greater than 50%) inhibition of isoproterenol-stimulated lipolysis. Inhibition of lipolysis equivalent to that seen with insulin, was achieved with ∼100 μM vanadium. In contrast, no insulin-like stimulation ofde novo fatty acid biosynthesis was observed with vanadium below 0.5 mM. Surprisingly, the antilipolytic effects of vanadium persisted in the presence of cilostamide, an inhibitor of the insulin-sensitive isoform of cyclic nucleotide phosphodiesterase. Studies with purified preparations of the catalytic subunit of cyclic AMP-dependent protein kinase revealed dose-dependent inhibition with vanadyl-glutathione (to a maximum of ∼40% inhibition). Equivalent inhibition of cyclic AMP-dependent phosphorylation of Kemptide (∼50%) was observed upon incubation of freshly-prepared fat-pad supernatant fractions with vanadyl-glutathione. These results suggest that effects of low concentrations of vanadium may be mediated, at least in part, by actions on the catalytic subunit of cyclic AMP-dependent protein kinase.
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References
Cahill GF: Physiology of insulin in man. Diabetes 20: 785–789, 1971
Moller DE, Flier JS: Insulin resistance — mechanisms, syndromes and implications. N Engl J Med 325: 938–948, 1991
Randle PJ, Priestman DA, Mistry SC, Halsall A: Glucose fatty acid interactions and the regulation of glucose disposal. J Cell Biochem 55: 1–11 (suppl), 1994
Randle PJ, Hales CN, Garland PB, Newsholme EA: The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1: 785–789, 1963
Nikkila EA: Control of plasma and liver triglyceride kinetics by carbohydrate metabolism and insulin. Adv Lipid Res 7: 63–134, 1969
Saudek CD, Eder HA: Lipid metabolism in diabetes mellitus. Am J Med 66: 843–852, 1979
Howard BV, Howard WJ: Dyslipidemia in non-insulin-dependent diabetes mellitus. Endocri Rev 15: 263–274, 1994
Ramanadham S, Mongold JJ, Brownsey RW, Cros GH, McNeill JH: Oral vanadyl sulfate in treatment of diabetes mellitus in rats. Am J Physiol 257: H904-H911, 1989
Ramanadham S, Brownsey RW, Cros GH, Mongold JJ, McNeill JH: Sustained prevention of myocardial and metabolic abnormalities in diabetic rats following withdrawal from oral vanadyl treatment. Metabolism, 38: 1022–1028, 1989
Duckworth WC, Solomon SS, Liepnieks J, Hamel FG, Hand S, Peavy DE: Insulin-like effects of vanadate in isolated rat adipocytes. Endocrinol 122: 2285–2289, 1988
Nilsson NO, Stralfors P, Fredrickson G, Belfrage P: Regulation of adipose tissue lipolysis: effects of noradrenaline and insulin on phosphorylation of hormone-sensitive lipase and lipolysis in intact rat adipocytes. FEBS Lett 111: 125–130, 1980
Loten EG, Sneyd JGT: An effect of insulin on adipose-tissue adenosine 3′,5′-cyclic monophosphate phosphodiesterase. Biochem J 120: 187–193, 1970
Degerman E, Smith CJ, Tornqvist H, Vasta V, Belfrage P, Manganiello VC: Evidence that insulin and isoprenaline activate the cGMP-inhibited low-Km cAMP phosphodiesterase in rat fat cells by phosphorylation. Proc Natl Acad Sci USA 87: 533–537, 1990
Shibata H, Robinson FW, Soderling TR, Kono T: Effects of okadaic acid on insulin-sensitive cAMP phosphodiesterase in rat adipocytes. Evidence that insulin may stimulate the enzyme by phosphorylation. J. Biol Chem 266: 17948–17953, 1991
Vasta V, Smith CJ, Calvo J, Belfrage P, Manganiello VC: Insulin and isoproterenol induce phosphorylation of the particulate cyclic GMP-inhibited, low Km cyclic AMP phosphodiesterase (cGI PDE) in 3T3-L1 adipocytes. Biochem Biophys Res Commun 183: 1070–1075, 1992
Sera M, Tanaka K, Morita T, Ueki H: Increasing effect of vanadate on lipoprotein lipase activity in isolated rat fat pads. Arch. Biochem. Biophys. 279: 291–297, 1990
Souness JE, Maslen C, Scott LC: Effects of solubilization and vanadate/glutathione complex on inhibitor potencies against eosinophil cyclic AMP-specific phosphodiesterase. FEBS Lett 302: 181–184, 1992
Ueki H, Okuhama R, Sera M, Inoue T, Tominaga N, Morita T: Stimulatory effect of vanadate on 3′,5′-cyclic guanosine monophosphate-inhibited low Michaelis-Menten constant 3′,5′-cyclic adenosine monophosphate phosphodiesterase activity in isolated rat fat pads. Endocrinol 131: 441–446, 1992
Brownsey RW, Dong GW, Lam V, McGreer W: Studies on protein phosphorylation using subcellular fractions from insulin-treated white adipose tissue of rats. Biochem. Cell Biol 66: 296–308, 1988
Rodbell M: Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 239: 375–380, 1964
Honnor RC, Dhillon GS, Londos C: cAMP-dependent protein kinase and lipolysis in rat adipocytes. 1. Cell preparation, manipulation and predictability in behaviour. J Biol Chem 260: 15122–15129, 1985
Winz R, Hess D, Aebersold R, Brownsey RW: Unique structural features and differential phosphorylation of the 280-kDa component (isozyme) of rat liver acetyl-CoA carboxylase. J Biol Chem 269: 14438–14445, 1994
Garland PB, Randle PJ: A rapid enzymatic assay for glycerol. Nature 196: 987–988, 1962
Stansbie D, Brownsey RW, Crettaz M, Denton RM: Acute effectsin vivo of anti-insulin serum on rates of fatty acid synthesis and activities of acetyl-coenzyme A carboxylase and pyruvate dehydrogenase in liver and epididymal adipose tissue of fed rats. Biochem J 160: 413–416, 1976
Casnellie JE: Assay of protein kinases using peptides with basic residues for phosphocellulose binding. Methods Enzymol. 200: 115–120, 1991
Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254, 1976
Crans DC: Aqueous chemistry of labile oxovanadates: relevance to biological studies. Comments Inorg Chem 16: 1–33, 1994
Chasteen ND, Francavilla J: An electron paramagnetic resonance study of vanadyl(IV)-serum albumin complexes. J Phys Chem 80: 867–871, 1976
Macara IG, Kustin K, Cantley LC: Glutathione reduces cytoplasmic vanadate — mechanism and physiological implications. Biochim Biophys Acta 629: 95–106, 1980
Sakurai H, Shimomura S, Fukuzawa K, Ishizu K: Detection of oxovanadium (IV) and characterization of its ligand environment in subcellular fractions of the liver of rats treated with pentav alent vanadium (V). Biochem Biophys Res Commun 96: 293–298, 1980
Nechay BR, Nanninga LB, Nechay PSE: Vanadyl (IV) and vanadate (V) binding to selected endogenous phosphate, carboxyl and amino ligands: calculations of cellular vanadium species distribution. Arch Biochem Biophys 251: 128–138, 1986
Chasteen ND: Vanadyl(IV) electron nuclear double resonance/electron spin echo envelope modulation spin probes. Methods Enzymol 237: 232–244, 1993
Shechter Y, Karlish SJD: Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions. Nature 284: 556–558, 1980
Ramanadham S, Heyliger C, Gresser MJ, Tracey AS, McNeill JH: The distribution and half-life for retention of vanadium in the organs of normal and diabetic rats orally fed vanadium (IV) and vanadium (V). Biol Trace Elem Res 30: 119–124, 1990
Hamel FG, Solomon SS, Jespersen AS, Blotcky A, Rack E, Duckworth WC: Alteration of tissue vanadium content in diabetes. Metabolism 42: 1503–1505, 1993
Schmitz-Peiffer C, Reeves ML, Denton RM: Characterization of the cyclic nucleotide phosphodiesterase isoenzymes present in rat epididymal fat cells. Cell Signalling 4: 37–49, 1992
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Brownsey, R.W., Dong, G.W. Evidence for selective effects of vanadium on adipose cell metabolism involving actions on cAMP-dependent protein kinase. Mol Cell Biochem 153, 131–137 (1995). https://doi.org/10.1007/BF01075928
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DOI: https://doi.org/10.1007/BF01075928