Summary
Withdrawal of exogenous insulin and a subsequent fast (24 h) of alloxan diabetic rats stimulated rates of gluconeogenesis, ureogenesis, ketogenesis, and amino acid release by in situ perfused livers when compared to those from normal, fasted rats. The contribution of liver glycogen to the high rates of gluconeogenesis observed with the diabetic liver could be excluded. Perfusate lactate concentrations remained constant during the period when the elevated rate of gluconeogenesis was observed with diabetic liver. Addition of insulin as a bolus (750 mU) and continuous infusion (12.5 mU/min) to the perfusion medium of diabetic livers resulted in constant perfusate levels of glucose, urea and α-amino nitrogen indicating a suppression of the catabolic processes present in the fasted, diabetic liver. The rate of ketogenesis was also slowed by insulin to about half the rate prior to addition of the hormone. These data indicate that insulin has an immediate anti-catabolic effect in the perfused, diabetic liver.
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Mortimore, G.E.: Effect of insulin on release of glucose and urea by isolated rat liver. Am. J. Physiol. 204, 699–704 (1963)
Mortimore, G.E., King, E., Jr., Mondon, C.E., Glinsmann, W.H.: Effects of insulin on net carbohydrate alterations in perfused rat liver. Am. J. Physiol. 212, 179–183 (1967)
Mondon, C.E., Mortimore, G.E.: Effects of insulin on amino acid release and urea formation in perfused rat liver. Am. J. Physiol. 212, 173–178 (1967)
Mortimore, G.E., Mondon, D.E.: Inhibition by insulin of valine turnover in liver. Evidence for a general control of proteolysis. J. Biol. Chem. 245, 2375–2383 (1970)
Heimberg, M., Dunkerley, A., Brown, T.O.: Hepatic lipid metabolism in experimental diabetes. I. Release and uptake of triglycerides by perfused livers from normal and alloxan-diabetic rats. Biochim. Biophys. Acta 125, 252–264 (1966)
Exton, J.H., Harper, S.C., Tucker, A.L., Ho, R.-J.: Effects of insulin on gluconeogenesis and cyclic AMP levels in perfused livers from diabetic rats. Biochim. Biophys. Acta 329, 23–40 (1973)
Söling, H.D., Kneer, P., Drägert, W., Creutzfeldt, W.: Die Wirkung von Insulin auf den Stoffwechsel der isolierten perfundierten Leber normaler und alloxandiabetischer Ratten. II. Stoffwechseländerungen unter dem Einfluß intraportaler Insulininfusionen. Diabetologia 2, 32–44 (1966)
Miller, L.L.: Some direct actions of insulin, glucagon, and hydrocortisone on the isolated perfused rat liver. Recent Prog. Horm. Res. 17, 539–564 (1961)
Haft, D.E., Miller, L.L.: Alloxan diabetes and demonstrated direct action of insulin on metabolim of isolated perfused rat liver. Am. J. Physiol. 192, 33–42 (1958)
Boden, G., Willms, B.: Einfluß von Insulin auf Kohlenhydrat und Fettstoffwechsel der perfundierten Leber bei normalen und Alloxan-diabetischen Ratten. Klin. Wochenschr. 44, 579–583 (1966)
Haft, D.E.: Studies of the metabolism of isolated livers of normal and alloxan-diabetic rats perfused with insulin. Diabetes 17, 244–250 (1968)
Hems, R., Ross, B.D., Berry, M.N., Krebs, H.A.: Gluconeogenesis in the perfused rat liver. Biochem. J. 101, 284–292 (1966)
Eilers, R.J.: Notification of final adoption of an international method and standard solution for hemoglobinometry specification for preparation of standard solution. Am. J. Clin. Pathol. 47, 212–214 (1967)
Krebs, H.A., Henseleit, K.: Untersuchungen über die Harnstoffbildung im Tierkörper. Hoppe Seylers Z. Physiol. Chem. 210, 33–66 (1932)
Wollenberger, A., Ristau, O., Schoffa, G.: Eine einfache Technik der extrem schnellen Abkühlung größerer Gewebestücke. Pfluegers Arch. 270, 399–412 (1960)
Lloyd, G.B., Whelan, W.J.: An improved method for enzymic determination of glucose in the presence of maltose. Anal. Biochem. 30, 467–469 (1969)
Hohorst, H.J.: L-(+)-lactate: Determination with lactic dehydrogenase and DPN. In: H.U. Bergmeyer (ed.): Methods of Enzymatic Analysis, pp. 266–270. New York and London: Academic Press 1965
Mellanby, J., Williamson, D.H.: Acetoacetate. In: H.U. Bergmeyer (ed.): Methods of Enzymatic Analysis, pp. 454–458. New York and London: Academic Press 1965
Williamson, D.H., Mellanby, J.: D-(-)-β-hydroxybutyrate. In: H.U. Bergmeyer (ed.): Methods of Enzymatic Analysis, pp. 459–461. New York and London: Academic Press 1965
Kaplan, A.P.: Urea nitrogen and urinary ammonia. In: S. Meites (ed.): Standard Methods of Clinical Chemistry, pp. 245–256. New York: Academic Press 1965
Rosen, H.: A modified ninhydrin colorimetric analysis for amino acids. Arch. Biochem. Biophys. 67, 10–15 (1967)
Huijing, F.: A rapid enzymatic method for glycogen estimation in very small tissue samples. Clin. Chim. Acta 30, 567–572 (1970)
Laurell, S.: A method for routine determination of plasma triglycerides. Scand. J. Clin. Lab. Invest. 18, 668–672 (1966)
Woodside, W.F., Heimberg, M.: Effects of anti-insulin serum, insulin, and glucose on output of triglycerides and on ketogenesis by the perfused rat liver. J. Biol. Chem. 251, 13–23 (1976)
Jefferson, L.S., Exton, J.H., Butcher, R.W., Sutherland, E.W., Park, C.R.: Role of adenosine 3′, 5′-monophosphate in the effects of insulin and anti-insulin serum on liver metabolism. J. Biol. Chem. 243, 1031–1038 (1968)
Menahan, L.A., Wieland, O.: Interaction of glucagon and insulin on the metabolism of perfused livers from fasted rats. Eur. J. Biochem. 9, 55–62 (1969)
Exton, J.H., Harper, S.C., Tucker, A.L., Flagg, J.L., Park, C.R.: Effects of adrenalectomy and glucocorticoid replacement on gluconeogenesis in perfused livers from diabetic rats. Biochim. Biophys. Acta 329, 41–57 (1973)
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Lombardo, Y.B., Hron, W.T. & Menahan, L.A. Effect of insulin in vitro on the isolated, perfused alloxan-diabetic rat liver. Diabetologia 14, 47–51 (1978). https://doi.org/10.1007/BF00429707
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DOI: https://doi.org/10.1007/BF00429707