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Fetal programming of perivenous glucose uptake reveals a regulatory mechanism governing hepatic glucose output during refeeding

Murphy, Helena C., Regan, Gemma, Bogdarina, Irina G., Clark, Adrian J.L., Iles, Richard A., Cohen, Robert D., Hitman, Graham A., Berry, Colin L., Coade, Zoe, Petry, Clive J. and Burns, Shamus P. (2003) Fetal programming of perivenous glucose uptake reveals a regulatory mechanism governing hepatic glucose output during refeeding. Diabetes, 52 (6). pp. 1326-1332. ISSN 0012-1797

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Abstract

Increased hepatic gluconeogenesis maintains glycemia during fasting and has been considered responsible for elevated hepatic glucose output in type 2 diabetes. Glucose derived periportally via gluconeogenesis is partially taken up perivenously in perfused liver but not in adult rats whose mothers were protein-restricted during gestation (MLP rats)—an environmental model of fetal programming of adult glucose intolerance exhibiting diminished perivenous glucokinase (GK) activity. We now show that perivenous glucose uptake rises with increasing glucose concentration (0–8 mmol/l) in control but not MLP liver, indicating that GK is flux-generating. The data demonstrate that acute control of hepatic glucose output is principally achieved by increasing perivenous glucose uptake, with rising glucose concentration during refeeding, rather than by downregulation of gluconeogenesis, which occurs in different hepatocytes. Consistent with these observations, glycogen synthesis in vivo commenced in the perivenous cells during refeeding, MLP livers accumulating less glycogen than controls. GK gene transcription was unchanged in MLP liver, the data supporting a recently proposed posttranscriptional model of GK regulation involving nuclear-cytoplasmic transport. The results are pertinent to impaired regulation of hepatic glucose output in type 2 diabetes, which could arise from diminished GK-mediated glucose uptake rather than increased gluconeogenesis.

Item Type: Article
Additional Information: © 2003 by the American Diabetes Association, Inc.
Uncontrolled Keywords: hepatic gluconeogenesis glycemia glucose diabetes
Subjects: Q Science > Q Science (General)
Q Science > QP Physiology
Q Science > QR Microbiology
Schools: School of Applied Sciences
References: REFERENCES 1. Rossetti L, Giaccari A, Barzilai N, Howard K, Sebel G, Hu M: Mechanism by which hyperglycemia inhibits hepatic glucose production in conscious rats. J Clin Invest 92:1126–1134, 1993 2. McGarry JD, Kuwajima M, Newgard CB, Foster DW: From dietary glucose to liver glycogen: the full circle round. Ann Rev Nutr 7:51–73, 1987 3. Newgard CB, Hirsch LJ, Foster DW, McGarry JD: Studies on the mechanism by which exogenous glucose is converted into liver glycogen in the rat. J Biol Chem 258:8046–8052, 1983 4. Newgard CB, Moore SV, Foster DW, McGarry JD: Efficient hepatic glycogen synthesis in refeeding rats requires continued flow through the gluconeogenic pathway. J Biol Chem 259:6958–6963, 1984 5. Ludvik B, Nolan JJ, Roberts J, Baloga M, Joyce J, Bell J, Olefsky JM: Evidence for decreased splanchnic glucose uptake after glucose administration in non-insulin dependent diabetes mellitus. J Clin Invest 100:2354– 2361, 1997 6. Liljenquist J, Meuller G, Cherrington A, Perry J, Rabinowitz D: Hyperglycaemia per se can inhibit glucose production in man. J Clin Endocrinol Metab 48:171–175, 1979 7. Basu A, Caumo A, Bettini F, Gelisio A, Alzaid A, Cobelli C, Rizza RA: Impaired basal glucose effectiveness in NIDDM. Contribution of defects in glucose disappearance and production, measured using an optimized minimal model independent protocol. Diabetes 46:421–432, 1997 8. Mevorach M, Giacca A, Aharon Y, Hawkins M, Shamoon H, Rossetti L: Regulation of endogenous glucose production by glucose per se is impaired in type 2 diabetes mellitus. J Clin Invest 102:744–753, 1998 9. Minassian C, Daniele N, Bordet JC, Zitoun C, Mithieux G: Liver glucose-6- phosphatase activity is inhibited by refeeding in rats. J Nutr 125:2727– 2732, 1995 10. Burns SP, Cohen RD, Iles RA, Germain JP, Going TCH, Evans SJW, Royston P: A method for the determination in situ of variations within the hepatic lobule of hepatocyte function and metabolite concentrations. Biochem J 319:377–383, 1996 11. Jungermann K, Katz N: Functional specialization of different hepatocyte populations. Physiol Rev 69:708–764, 1989 12. Burns SP, Desai M, Cohen RD, Hales CN, Iles RA, Germain JP, Going TCH, Bailey RA: Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation. J Clin Invest 100:1768–1774, 1997 13. Toyoda Y, Miwa I, Kamiya M, Ogiso S, Nonogaki N, Aoki S, Okuda J: Tissue and subcellular distribution of glucokinase in rat liver and their changes during fasting-refeeding. Histochemistry 103:31–38, 1995 14. Burns SP, Murphy HC, Iles RA, Bailey RA, Cohen RD: Hepatic intralobular mapping of fructose metabolism in the rat liver. Biochem J 349:539–545, 2000 15. Hales CN, Barker DJP: Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 35:595–601, 1992 16. Hales CN, Desai M, Ozanne SE, Crowther NJ: Fishing in the stream of diabetes: from measuring insulin to the control of fetal organogenesis. Biochem Soc Trans 24:341–350, 1996 17. Cohen RD, Iles RA Barnett D, Howell MEO, Strunin J: The effect of change in lactate uptake on the intracellular pH of the perfused rat liver. Clin Sci 41:159–170, 1971 18. Krebs HA, Henseleit K: Untersuchungen u¨ ber die Harnstoffbildung im Tierko¨ rper. Hoppe-Seylers Zeitschr Physiol Chem 210:33–36, 1932 19. Davidson AL, Arion WJ: Factors underlying significant underestimations of glucokinase activity in crude liver extracts: physiological implications of higher cellular activity. Arch Biochem Biophys 253:156–167, 1987 20. Babcock MB, Cardell RR: Hepatic glycogen patterns in fasted and fed rats. Am J Anat 140:299–338, 1974 21. Moorman AF, de Boer PA, Charles R, Lamers WH: Pericentral expression pattern of glucokinase RNA in the rat liver lobulus. FEBS Lett 287:47–52, 1991 22. Rossetti L, Chen W, Hu M, Hawkins M, Barzilai N, Efrat S: Abnormal regulation of HGP by hyperglycemia in mice with a disrupted glucokinase allele. Am J Physiol 273: E743–E750, 1997 23. Matschinsky FM: Glucokinase as glucose sensor and metabolic signal generator in pancreatic beta-cells and hepatocytes. Diabetes 39:647–652, 1990 24. Kurland IJ, Pilkis SJ: Indirect versus direct routes of hepatic glycogen synthesis. FASEB J 3:2277–2281, 1989 25. Kuwajima M, Golden S, Katz J, Unger RH, Foster DW, McGarry JD: Active hepatic glycogen synthesis from gluconeogenic precursors despite high tissue levels of fructose 2,6-bisphosphate. J Biol Chem 261:2632–2637, 1986 26. Seoane J, Gomez-Foix AM, O’Doherty R, Gomez-Ara C, Newgard CB, Guinovart JJ: Glucose 6-phosphate produced by glucokinase, but not hexokinase 1, promotes the activation of hepatic glycogen synthase. J Biol Chem 271:23756–23760, 1996 27. Gomis RR, Cid E, Garcia-Rocha M, Ferrer JC Guinovart JJ: Liver glycogen synthase but not the muscle isoform differentiates between glucose 6-phosphate produced by glucokinase or hexokinase. J Biol Chem 277: 23246–23252, 2002 28. Agius L, Peak M, Newgard CB, Gomez-Foix AM, Guinovart JJ: Evidence for a role of glucose-induced translocation of glucokinase in the control of hepatic glycogen synthesis. J Biol Chem 271:30479–30486, 1996 29. Gomis RR, Ferrer JC Guinovart JJ: Shared control of hepatic glycogen synthesis by glycogen synthase and glucokinase. Biochem J 351:811–816, 2000 30. Iynedjian PB, Gjinovci A, Renold AE: Stimulation by insulin of glucokinase gene transcription in liver of diabetic rats. J Biol Chem 263:740–744, 1988 31. Iynedjian PB, Jotterand D, Nouspikel T, Asfari M, Pilot P-R: Transcriptional induction of glucokinase gene by insulin in cultured liver cells and its repression by the glucagon-cAMP system. J Biol Chem 264:21824–21829, 1989 32. Vandercammen A, Van Schaftingen E: Species and tissue distribution of the regulatory protein of glucokinase. Biochem J 294:551–556, 1993 33. Fernandez-Novell JM, Castel S, Bellido D, Ferrer JC, Vilaro S, Guinovart JJ: Intracellular distribution of hepatic glucokinase and glucokinase regulatory protein during the fasted to refed transition in rats. FEBS Lett 459:211–214, 1999 34. Farrelly D, Brown KS, Tieman A, Ren J, Lira SA, Hagan D, Gregg R, Mookhtiar KA, Hariharan N: Mice mutant for GK regulatory protein exhibit decreased liver GK: a sequestration mechanism in metabolic regulation. Proc Natl Acad Sci U S A 96:14511–14516, 1999 35. Grimsby J, Coffey JW, Dvorozniak MT, Magram J, Li G, Matschinsky FM, Shiota C, Kaur S, Magnuson MA, Grippo JF: Characterization of glucokinase regulatory protein-deficient mice. J Biol Chem 275:7826–7831, 2000 36. Cohen RD: Roles of the liver and kidney in acid-base regulation and its disorders. Br J Anaesth 67:154–164, 1991 37. Magnusson R, Rothman DL, Katz LD, Shulman RG, Shulman GI: Increased rate of gluconeogenesis in type II diabetes mellitus: a 13C nuclear magnetic resonance study. J Clin Invest 90:1323–1327, 1992
Depositing User: Sara Taylor
Date Deposited: 20 Dec 2007
Last Modified: 06 Apr 2018 16:52
URI: http://eprints.hud.ac.uk/id/eprint/203

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