Download PDF
Horm Metab Res 2006; 38(1): 1-7
DOI: 10.1055/s-2006-924964
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Expression of Glucose-6-phosphatase System Genes in Murine Cortex and Hypothalamus

B.-H.  Goh1 , A.  Khan1 , S.  Efendić1 , N.  Portwood1
  • 1 The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
Further Information

Publication History

Received 19 May 2005

Accepted after revision 29 August 2005

Publication Date:
13 February 2006 (online)

Also available at
    Permissions and Reprints

Abstract

The glucose-6-phosphatase (G6Pase) system participates in the regulation of glucose homeostasis by converting glucose-6-phosphate (G6P) into glucose and inorganic phosphates. We have used an RT-PCR-based cloning and sequencing approach to study the expression of components of the G6Pase system in the hypothalamus and cortex tissues of the ob/ob mouse. We observed the expression of hepatic G6Pase catalytic subunit, G6PC, in both tissues, although increased template inputs were required for its detection. Conversely, expression of both the mouse homologue of the previously-described brain-specific G6P translocase T1 (G6PT1) variant and of the hepatic G6PT1 isoform was easily detectable in hypothalamus and cortex tissues. Of the proposed G6Pase catalytic subunit homologues, the expression of murine ubiquitous G6Pase catalytic subunit-related protein (UGRP, G6PC3) was also easily detectable in both tissues. However, islet-specific G6Pase catalytic subunit-related protein (IGRP, G6PC2) was expressed in a tissue-specific manner, and was detectable only in hypothalamus tissue at increased template inputs. We conclude that cells within ob/ob mouse hypothalamus and cortex tissues express genes with either established or proposed roles in G6P hydrolysis.

Key words

Cortex - G6PC - G6PC2 - G6PC3 - G6PT1 - glucose-6-phosphate - ob/ob

References

  • 1 Nordlie R C. Glucose-6-Phosphatase-Phosphotransferase: Roles and Regulation in Relation to Gluconeogenesis. In: Hanson RW, Mehlman MA (eds) Gluconeogenesis: its regulation in mammalian species. New York; John Wiley & Sons Inc 1976: 93-152
    Google Scholar
  • 2 van de Werve G, Lange A, Newgard C, Méchin M-C, Li Y, Berteloot A. New lessons in the regulation of glucose metabolism taught by the glucose-6-phosphatase system.  Eur J Biochem. 2000;  267 1533-1549
    CrossrefPubMedGoogle Scholar
  • 3 Shelly L L, Lei K-J, Pan C-J, Sakata S F, Ruppert S, Schultz G, Chou J Y. Isolation of the gene for murine glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1a.  J Biol Chem. 1993;  268 21 482-21 485
    PubMedGoogle Scholar
  • 4 Gerin I, Veiga-da-Cunha M, Achouri Y, Collet J F, van Schaftingen E. Sequence of a putative glucose-6-phosphate translocase, mutated in glycogen storage disease type 1b.  FEBS Lett. 1997;  419 235-238
    CrossrefPubMedGoogle Scholar
  • 5 Ashmore J, Hastings A B, Nesbett F B. The effect of diabetes and fasting on liver glucose-6-phosphatase.  Proc Natl Acad Sci USA. 1954;  40 673-678
    PubMedGoogle Scholar
  • 6 Segal H L, Washko M E. Studies of liver glucose-6-phosphatase. III. Solubilization and properties of the enzyme from normal and diabetic rats.  J Biol Chem. 1959;  234 1937-1941
    PubMedGoogle Scholar
  • 7 Liu Z Q, Barrett E J, Dalkin A C, Zwart A D, Chou J Y. Effect of acute diabetes on rat hepatic glucose-6-phosphatase activity and its messenger RNA level.  Biochem Biophys Res Commun. 1994;  205 680-686
    CrossrefPubMedGoogle Scholar
  • 8 Massillon D, Barzilai N, Chen W, Hu M, Rossetti L. Glucose regulates in vivo glucose-6-phosphatase gene expression in the liver of diabetic rats.  J Biol Chem. 1996;  271 9871-9874
    CrossrefPubMedGoogle Scholar
  • 9 Li Y, Méchin M-C, van de Werve G. Diabetes affects similarly the catalytic subunit and putative glucose-6-phosphate translocase of glucose-6-phosphatase.  J Biol Chem. 1999;  274 33 866-33 868
    PubMedGoogle Scholar
  • 10 Arden S D, Zahn T, Steegers S, Webb S, Bergman B, O’Brien R M, Hutton J C. Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit-related protein.  Diabetes. 1999;  48 531-542
    CrossrefPubMedGoogle Scholar
  • 11 Martin C C, Oeser J K, Svitek C A, Hunter S I, Hutton J C, O’Brien R M. Identification and characterization of a human cDNA and gene encoding a ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein.  J Mol Endocrinol. 2002;  29 205-222
    CrossrefPubMedGoogle Scholar
  • 12 Petrolonis A J, Yang Q, Tummino P J, Fish S M, Prack A E, Jain S, Parsons T F, Li P, Dales N A, Ge L, Langston S P, Schuller A G, An W F, Tartaglia L A, Chen H, Hong S B. Enzymatic characterization of the pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP).  J Biol Chem. 2004;  279 13 976-13 983
    PubMedGoogle Scholar
  • 13 Guionie O, Clottes E, Stafford K, Burchell A. Identification and characterization of a new human glucose-6-phosphatase isoform.  FEBS Lett. 2003;  551 159-164
    CrossrefPubMedGoogle Scholar
  • 14 Boustead J N, Martin C C, Oeser J K, Svitek C A, Hunter S I, Hutton J C, O’Brien R M. Identification and characterization of a cDNA and the gene encoding the mouse ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein.  J Mol Endocrinol. 2004;  32 33-53
    CrossrefPubMedGoogle Scholar
  • 15 Shieh J J, Pan C J, Mansfield B C, Chou J Y. A glucose-6-phosphate hydrolase, widely expressed outside the liver, can explain age-dependent resolution of hypoglycemia in glycogen storage disease type Ia.  J Biol Chem. 2003;  278 47 098-47 103
    PubMedGoogle Scholar
  • 16 Lin B, Annabi B, Hiraiwa H, Pan C-J, Chou J Y. Cloning and characterization of cDNAs encoding a candidate glycogen storage disease type 1b protein in rodents.  J Biol Chem. 1998;  273 31 656-31 660
    PubMedGoogle Scholar
  • 17 Lin B, Pan C-J, Chou J-Y. Human variant glucose-6-phosphate transporter is active in microsomal transport.  Hum Genet. 2000;  107 526-529
    PubMedGoogle Scholar
  • 18 Martin C C, Bischof L J, Bergman B, Hornbuckle L A, Hilliker C, Frigeri C, Wahl D, Svitek C A, Wong R, Goldman J K, Oeser J K, Lepetre F, Froguel P, O’Brien R M, Hutton J C. Cloning and characterization of the human and rat islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) genes.  J Biol Chem. 2001;  276 25 197-25 207
    PubMedGoogle Scholar
  • 19 Rajas F, Bruni N, Montano S, Zitoun A, Mithieux G. The glucose-6 Phosphatase Gene Is Expressed in Human and Rat Small Intestine: Regulation of Expression in Fasted and Diabetic Rats.  Gastroenterology. 1999;  117 132-139
    CrossrefPubMedGoogle Scholar
  • 20 Goh B-H, Efendić S, Khan A, Portwood N. Evidence for the expression of both the hydrolase and translocase components of hepatic glucose-6-phosphatase in murine pancreatic islets.  Biochem Biophys Res Comm. 2003;  307 935-941
    CrossrefPubMedGoogle Scholar
  • 21 Colilla W, Jorgenson R A, Nordlie R C. Mammalian Carbamyl Phosphate: Glucose Phosphotransferase and Glucose-6-phosphate Phosphohydrolase: Extended Tissue Distribution.  Biochim Biophys Acta. 1975;  377 117-125
    PubMedGoogle Scholar
  • 22 Huang M-T, Veech R L. The Quantitative Determination of the in vivo Dephosphorylation of Glucose 6-Phosphate in Rat Brain.  J Biol Chem. 1982;  257 11 358-11 363
    PubMedGoogle Scholar
  • 23 Khan A, Zong-Chao L, Efendić S, Landau B R. Glucose-6-Phosphatase Activity in the Hypothalamus of the ob/ob Mouse.  Metab Clin Exp. 1998;  47 627-629
    PubMedGoogle Scholar
  • 24 Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J M. Positional cloning of the mouse obese gene and its human homologue.  Nature. 1994;  372 425-432
    CrossrefPubMedGoogle Scholar
  • 25 Schwartz M W, Seeley R J, Campfield L A, Burn P, Baskin D G. Identification of Targets of Leptin Action in Rat Hypothalamus.  J Clin Invest. 1996;  98 1101-1106
    CrossrefPubMedGoogle Scholar
  • 26 Wynne K, Stanley S, McGowan B, Bloom S. Appetite control.  J Endocrinol. 2005;  184 291-318
    CrossrefPubMedGoogle Scholar
  • 27 Slotnick B M, Leonard C M. A Stereotaxic Atlas of the Albino Mouse Forebrain. Rockville, MD; US Department of Health, Education, and Welfare, Alcohol, Drug Abuse and Mental Health Administration 1975
    Google Scholar
  • 28 Tadros H, Chrétien M, Mbikay M. The testicular germ-cell protease PC4 is also expressed in macrophage-like cells of the ovary.  J Reprod Immunol. 2001;  49 133-152
    PubMedGoogle Scholar
  • 29 Middleditch C, Clottes E, Burchell A. A different isoform of the transport protein mutated in glycogen storage disease 1b is expressed in brain.  FEBS Lett. 1998;  433 33-36
    CrossrefPubMedGoogle Scholar
  • 30 Forsyth R J, Bartlett K, Burchell A, Scott H M, Eyre J A. Astrocytic glucose-6-phosphatase and the permeability of brain microsomes to glucose 6-phosphate.  Biochem J. 1993;  294 145-151
    PubMedGoogle Scholar
  • 31 Anuradha B, Varalakshmi P. Activities of Glucose-metabolizing Enzymes in Experimental Neurotoxic Models with Lipoate as an Alleviator.  J Appl Toxicol. 1999;  19 405-409
    CrossrefPubMedGoogle Scholar
  • 32 Ghosh A, Cheung Y Y, Mansfield B C, Chou J Y. Brain Contains a Functional Glucose-6-Phosphatase Complex Capable of Endogenous Glucose Production.  J Biol Chem. 2005;  280 11 114-11 119
    PubMedGoogle Scholar
  • 33 Palkovits M. Micro- and Macroscopic Structure, Innervation, and Vasculature of the Hypothalamus. In: Conn PM, Freeman ME (eds) Neuroendocrinology in Physiology and Medicine. New Jersey; Humana Press Inc 2000: 23-40
    Google Scholar

Neil Portwood

The Rolf Luft Center for Diabetes Research · Department of Molecular Medicine and Surgery · Karolinska Institute

SE-171 76 · Stockholm · Sweden ·

Phone: +46 (8) 517 73398/+46 (8) 517 79459

Fax: +46 (8) 517 73658

Email: Neil.Portwood@molmed.ki.se

      >