Hostname: page-component-cd9895bd7-dzt6s Total loading time: 0 Render date: 2024-12-27T02:57:06.624Z Has data issue: false hasContentIssue false
  • English
  • Français

Effects of pulsatile secretion of growth hormone (GH) on fat deposition in human GH transgenic rats

Published online by Cambridge University Press:  19 February 2013

Yasufumi Furuhata ,
Masugi Nishihara  and
Michio Takahashi
Yasufumi Furuhata*
Affiliation:
Department of Veterinary Physiology, Veterinary Medical Science, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
Masugi Nishihara
Affiliation:
Research Institute for Health Fundamentals, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki-shi, 210-0801, Japan
Michio Takahashi*
Affiliation:
Department of Veterinary Physiology, Veterinary Medical Science, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
*
†Dr M. Takahashi, fax +81 44 244 9617, email [email protected]
†Dr M. Takahashi, fax +81 44 244 9617, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Growth hormone (GH) is an endocrine regulator of glucose and lipid metabolism as well as body growth. GH levels are decreased and a unique pulsatile secretory pattern becomes obvious after puberty particularly in males. Coincidentally with this, males tend to deposit body fat. Experimental and clinical evidence has accumulated that obesity is associated with a decrease in GH levels. A strain of transgenic rats has been generated with severe obesity but normal nose-to-tail length, which has low circulating GH levels without pulsatility (human growth hormone (hGH) transgenic rats). The present review mainly focuses on recent and current work analysing the relationship between the occurrence of obesity and low GH levels and/or the absence of GH pulsatility in this transgenic animal model. This model has elevated blood glucose, non-esterified fatty acid, insulin and leptin levels associated with hyperphagia, suggesting that these rats also carry insulin- and leptin-resistant characteristics. hGH transgenic rats were subjected to a pair-feeding treatment to normalize food intake and chronic GH replacement to normalize GH levels. While the pair-feeding for 8 weeks successfully suppressed body-weight gain, the fat pad : body weight ratio remained very similar to freely-eating control hGH transgenic rats, which indicates the hyperphagia is not the sole contributor to the excess fat accumulation in this model. However, continuous elevation of peripheral hGH levels (approximately 2-fold) for 8 weeks by means of a slow-release vehicle resulted in a significant decrease in the fat mass : body weight ratios by 30 %. This GH treatment altered neither food intake nor body-weight gain. Thus, two characteristic phenotypes observed in the hGH transgenic rats, hyperphagia and obesity, seem to be closely related to GH levels and GH secretory pattern. This relationship might be working in the regulation of changes in seasonal body composition in wild animals.

Keywords

Growth hormoneTransgenic ratsObesityBody composition
Type
Research Article
Information
Nutrition Research Reviews , Volume 15 , Issue 2 , December 2002 , pp. 231 - 244
Copyright
Copyright © CABI Publishing 2002

References

Almira, EC & Reddy, WJ (1979) Effect of fasting on insulin binding to hepatocytes and liver plasma membranes from rats. Endocrinology 104, 205–211.CrossRefGoogle ScholarPubMed
Anai, M, Funaki, M, Ogihara, T, Terasaki, J, Inukai, K, Katagiri, H, Fukushima, Y, Yazaki, Y, Kikuchi, M, Oka, Y & Asano, T (1998) Altered expression levels and impaired steps in the pathway to phosphatidylinositol 3-kinase activation via insulin receptor substrates 1 and 2 in Zucker fatty rats. Diabetes 47, 13–23.CrossRefGoogle ScholarPubMed
Banks, WA, Huang, AJ, Jaspan, JB & Maness, LM (1996) Leptin enters the brain by a saturable system independent of insulin. Peptides 17, 305–311.CrossRefGoogle ScholarPubMed
Beauville, M, Harant, I, Crampes, F, Riviere, D, Tauber, MT, Tauber, JP & Garrigues, M (1992) Effect of long-term rhGH administration in GH-deficient adults on fat cell epinephrine response. American Journal of Physiology 263, E467–E472.Google ScholarPubMed
Bengtsson, BA, Eden, S, Lonn, L, Kvist, H, Stokland, A, Lindstedt, G, Bosaeus, I, Tolli, J, Sjostrom, L & Isaksson, OG (1993) Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. Journal of Clinical Endocrinology and Metabolism 76, 309–317.Google ScholarPubMed
Bjarnason, R, Boguszewski, M, Dahlgren, J, Gelander, L, Kristrom, B, Rosberg, S, Carlsson, B, Albertsson-Wikland, K & Carlsson, LM (1997) Leptin levels are strongly correlated with those of GH-binding protein in prepubertal children. European Journal of Endocrinology 137, 68–73.CrossRefGoogle ScholarPubMed
Bjorntorp, P, Bergman, H, Varnauskas, E & Lindholm, B (1969) Lipid mobilization in relation to body composition in man. Metabolism: Clinical and Experimental 18, 840–851.CrossRefGoogle ScholarPubMed
Boyer, BB, Ormseth, OA, Buck, L, Nicolson, M, Pelleymounter, MA & Barnes, BM (1997) Leptin prevents posthibernation weight gain but does not reduce energy expediture in arctic ground squirrels. Comparative Biochemistry and Physiology 118, 405–412.Google ScholarPubMed
Brown-Borg, HM, Borg, KE, Meliska, CJ & Bartke, A (1996) Dwarf mice and the ageing process. In Nature. 384, 33.CrossRefGoogle ScholarPubMed
Burguera, B, Couce, ME, Curran, GL, Jensen, MD, Lloyd, RV, Cleary, MP & Poduslo, JF (2000) Obesity is associated with a decreased leptin transport across the blood-brain barrier in rats. Diabetes 49, 1219–1223.CrossRefGoogle ScholarPubMed
Caro, JF, Kolaczynski, JW, Nyce, MR, Ohannesian, JP, Opentanova, I & Goldman, WH (1996) Decreased cerebrospinal-fluid serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 348, 159–161.CrossRefGoogle ScholarPubMed
Cheatham, B, Vlahos, CJ, Cheatham, L, Wang, L, Blenis, J & Kahn, CR (1994) Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Molecular and Cellular Biology 14, 4902–4911.Google ScholarPubMed
Chen, H, Charlat, O, Tartaglia, LA, Woolf, EA, Weng, X, Ellis, SJ, Lakey, ND, Culpepper, J, Moore, KJ, Breitbart, RE, Duyk, GM, Tepper, RI & Morgenstern, JP (1996) Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice. Cell 84, 491–495.CrossRefGoogle ScholarPubMed
Chua, SC, Chung, WK, Wu-peng, XS, Zhang, Y, Liu, SM, Tartaglia, L, & Leibel, RL (1996) Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (Leptin) receptor. Science 271, 994–996.CrossRefGoogle ScholarPubMed
Clark, RG, Mortensen, DL, Carlsson, LM, Carlsson, B, Carmignac, D & Robinson, IC (1996) The obese growth hormone (GH)-deficient dwarf rat: body fat responses to patterned delivery of GH and insulin-like growth factor-I. Endocrinology 137, 1904–1912.CrossRefGoogle ScholarPubMed
Cuneo, RC, Salomon, F, McGauley, GA & Sonksen, PH (1992) The growth hormone deficiency syndrome in adults. Clinical Endocrinology 37, 387–397.CrossRefGoogle ScholarPubMed
Cusin, I, Sainsbury, A, Doyle, P, Rohner-Jeanrenaud, F & Jeanrenaud, B (1995) The ob gene and insulin. A relationship leading to clues to the understanding of obesity. Diabetes 44, 1467–1470.CrossRefGoogle Scholar
Daugaard, JR, Laustsen, JL, Hansen, BS & Richter, EA (1999) Insulin action in growth hormone-deficient and age-matched control rats: effect of growth hormone treatment. Journal of Endocrinology 160, 127–135.CrossRefGoogle ScholarPubMed
Davidson, MB (1987) Effect of growth hormone on carbohydrate and lipid metabolism. Endocrine Reviews 8, 115–131.CrossRefGoogle ScholarPubMed
de Boer, H, Blok, GJ & Van der Veen, EA (1995) Clinical aspects of growth hormone deficiency in adults. Endocrine Reviews 16, 63–86.CrossRefGoogle ScholarPubMed
Dominici, FP, Arostegui Diaz, G, Bartke, A, Kopchick, J & Turyn, D (2000) Compensatory alterations of insulin signal transduction in liver of growth hormone receptor knockout mice. Journal of Endocrinology 166, 579–590.CrossRefGoogle ScholarPubMed
Dominici, FP, Balbis, A, Bartke, A & Turyn, D (1998) Role of hyperinsulinemia on hepatic insulin receptor concentration and autophosphorylation in the presence of high growth hormone levels in transgenic mice overexpressing growth hormone gene. Journal of Endocrinology 159, 15–25.CrossRefGoogle ScholarPubMed
Dominici, FP, Cifone, D, Bartke, A & Turyn, D (1999) Loss of sensitivity to insulin at early events of the insulin signaling pathway in the liver of growth hormone-transgenic mice. Journal of Endocrinology 161, 383–392.CrossRefGoogle ScholarPubMed
Eisen, EJ, Peterson, CB, Parker, IJ & Murray, JD (1998) Effects of zinc ion concentration on growth, fat content and reproduction in oMT1a-oGH transgenic mice. Growth, Development, and Aging 62, 173–186.Google ScholarPubMed
Fain, JN, Ihle, JH & Bahouth, SW (1999) Stimulation of lipolysis but not of leptin release by growth hormone is abolished in adipose tissue from Stat5a and b knockout mice. Biochemical and Biophysical Research Communications 263, 201–205.CrossRefGoogle Scholar
Fielder, PJ & Talamantes, F (1987) The lipolytic effects of mouse placental lactogen, mouse prolactin, and mouse growth hormone on adipose tissue from virgin and pregnant mice. Endocrinology 121, 493–497.CrossRefGoogle ScholarPubMed
Fisker, S, Vahl, N, Hansen, TB, Jorgensen, JO, Hagen, C, Orskov, H & Christiansen, JS (1997) Serum leptin is increased in growth hormone-deficient adults: relationship to body composition and effects of placebo-controlled growth hormone therapy for 1 year. Metabolism: Clinical and Experimental 46, 812–817.CrossRefGoogle ScholarPubMed
Furuhata, Y, Hirabayashi, K, Yonezawa, T, Takahashi, M & Nishihara, M (2002 a) Effects of pair-feeding and growth hormone treatment on obese transgenic rats. European Journal of Endocrinology 146, 245–249.CrossRefGoogle ScholarPubMed
Furuhata, Y, Kagaya, R, Hirabayashi, K, Ikeda, A, Chang, KT, Nishihara, M & Takahashi, M (2000) Development of obesity in transgenic rats with low circulating growth hormone levels: involvement of leptin resistance. European Journal of Endocrinology 143, 535–541.CrossRefGoogle ScholarPubMed
Furuhata, Y, Yonezawa, T, Takahashi, M & Nishihara, M (2002 b) Impaired insulin signaling in the liver of transgenic rats with low circulating growth hormone. Journal of Endocrinology 172, 127–136.CrossRefGoogle ScholarPubMed
Gabbay, RA, Sutherland, C, Gnudi, L, Kahn, BB, O'Brien, RM, Granner, DK & Flier, JS (1996) Insulin regulation of phosphoenolpyruvate carboxykinase gene expression does not require activation of the Ras/mitogen-activated protein kinase signaling pathway. Journal of Biological Chemistry 271, 1890–1897.CrossRefGoogle Scholar
Gavin, JR III, Roth, J, Neville, DM Jr, Meyts, PD & Buell, DN (1974) Insulin-dependent regulation of insulin receptor concentrations: a direct demonstration in cell culture. Proceedings of the National Academy of Sciences USA 71, 84–88.CrossRefGoogle ScholarPubMed
Ghilardi, N, Zingler, S, Wiestner, A, Soffel, R & Heim, MH (1996) Defective STAT signaling by leptin receptor in diabetic mice. Proceedings of the National Academy of Sciences USA 93, 6231–6235.CrossRefGoogle ScholarPubMed
Goodman, HM & Grichting, G (1983) Growth hormone and lipolysis: a reevaluation. Endocrinology 113, 1697–1702.CrossRefGoogle ScholarPubMed
Günzburg, WH, Salmons, B, Zimmermann, B, Müller, M, Erfle, V & Brem, G (1991) A mammary-specific promoter directs expression of growth hormone not only to the mammary gland, but also to bergman glia cells in transgenic mice. Molecular Endocrinology 5, 123–133.CrossRefGoogle ScholarPubMed
Hansen, LH, Madsen, B, Teisner, B & Nielsen, JH & Billestrup, N (1998) Characterization of the inhibitory effect of growth hormone on primary preadipocyte differentiation. Molecular Endocrinology 12, 1140–1149.CrossRefGoogle ScholarPubMed
Hardie, LJ, Guilhot, N & Trayhurn, P (1996) Regulation of leptin production in cultured mature white adipocytes. Hormone and Metabolic Research 28, 685–689.CrossRefGoogle ScholarPubMed
Hew, FL, Koschmann, M, Christopher, M, Rantzau, C, Vaag, A, Ward, G, Beck-Nielsen, H & Alford, F (1996) Insulin resistance in growth hormone-deficient adults: defects in glucose utilization and glycogen synthase activity. Journal of Clinical Endocrinology and Metabolism 81, 555–564.Google ScholarPubMed
Hickey, MS, Israel, RG, Gardiner, SN, Considine, RV, McCammon, MR, Tyndall, GL, Houmard, JA, Marks, RH & Caro, JF (1996) Gender differences in serum leptin levels in humans. Biochemical Molecular Medicine 59, 591–616.CrossRefGoogle ScholarPubMed
Hotamisligil, GS, Peraldi, P, Budavari, A, Ellis, R, White, MF & Spiegelman, BM (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271, 665–668.CrossRefGoogle ScholarPubMed
Ikeda, A, Chang, KT, Matsumoto, Y, Furuhata, Y, Nishihara, M, Sasaki, F & Takahashi, M (1998) Obesity and insulin resistance in human growth hormone transgenic rats. Endocrinology 139, 3057–3063.CrossRefGoogle ScholarPubMed
Ikeda, A, Matsuyama, S, Nishihara, M, Tojo, H & Takahashi, M (1994) Changes in endogenous growth hormone secretion and onset of puberty in transgenic rats expressing human growth hormone gene. Endocrine Journal 41, 523–529.CrossRefGoogle ScholarPubMed
Janssen, YJH, Frolich, M, Deurenberg, P & Roelfsema, F (1997) Serum leptin levels during recombinant human GH therapy in adults with GH deficiency. European Journal of Endocrinology 137, 650–654.CrossRefGoogle ScholarPubMed
Johansson, JO, Fowelin, J, Landin, K, Lager, I & Bengtsson, BA (1995) Growth hormone-deficient adults are insulin-resistant. Metabolism: Clinical and Experimental 44, 1126–1129.CrossRefGoogle ScholarPubMed
Kahn, CR, Goldfine, ID, Neville, DM Jr & De Meyts, P (1978) Alterations in insulin binding induced by changes in vivo in the levels of glucocorticoids and growth hormone. Endocrinology 103, 1054–1066.CrossRefGoogle ScholarPubMed
Kamel, A, Norgren, S, Elimam, A, Danielsson, P & Marcus, C (2000) Effects of growth hormone treatment in obese prepubertal boys. Journal of Clinical Endocrinology & Metabolism 85, 1412–1419.Google ScholarPubMed
Kanai, F, Ito, K, Todaka, M, Hayashi, H, Kamohara, S, Ishii, K, Okada, T, Hazeki, O, Ui, M & Ebina, Y (1993) Insulin-stimulated GLUT4 translocation is relevant to the phosphorylation of IRS-1 and the activity of PI3-kinase. Biochemical anad Biophysical Research Communications 195, 762–768.CrossRefGoogle Scholar
Kanety, H, Feinstein, R, Papa, MZ, Hemi, R & Karasik, A (1995) Tumor necrosis factor α-induced phosphorylation of insulin receptor substrate-1 (IRS-1). Possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1. Journal of Biological Chemistry 270, 23780–23784.CrossRefGoogle ScholarPubMed
Kato, R & Yamazoe, Y (1993) Hormonal regulation of cytochrome P450 in rat liver. In Cytochrome P450: Handbook of Experimental Pharmacology. vol. 105 pp. 447–459 [John, BS and Helmut, G editors]. Berlin: Springer.CrossRefGoogle Scholar
Kopchick, JJ, Bellush, LL & Coschigano, KT (1999) Transgenic models of growth hormone action. Annual Review of Nutrition 19, 437–461.CrossRefGoogle ScholarPubMed
Kopelman, PG (2000) Obesity as a medical problem. Nature 404, 635–643.CrossRefGoogle ScholarPubMed
Kunz, TH, Wrazen, JA & Burnett, CD (1998) Changes in body mass and body composition in pre-hibernating little brown bats (Myotis lucifugus). Ecoscience 5, 8–17.CrossRefGoogle Scholar
Lee, GH, Proenca, R, Montez, JM, Carroll, KM, Darvishzadeh, JG, Lee, JI & Friedman, JM (1996) Abnormal splicing of the leptin receptor in diabetic mice. Nature 379, 632–635.CrossRefGoogle ScholarPubMed
Lesniak, MA & Roth, J (1976) Regulation of receptor concentration by homologous hormone. Effect of human growth hormone on its receptor in IM-9 lymphocytes. Journal of Biological Chemistry 251, 3720–3729.CrossRefGoogle ScholarPubMed
Levin, N, Nelson, C, Gurney, A, Vandlen, R & de Sauvage, F (1996) Decreased food intake does not completely account for adiposity reduction after ob protein infusion. Proceedings of the National Academy of Sciences of the United States of America 93, 1726–1730.CrossRefGoogle Scholar
McKinley, MJ & Oldfield, BJ (1998) The brain as an endocrine target for peptide hormones. Trends in Endocrinology and Metabolism 9, 349–354.CrossRefGoogle ScholarPubMed
Maloff, BL, Levine, JH & Lockwood, DH (1980) Direct effects of growth hormone on insulin action in rat adipose tissue maintained in vitro. Endocrinology 107, 538–544.CrossRefGoogle ScholarPubMed
Merimee, TJ, Felig, P, Marliss, E, Fineberg, SE & Cahill, GG Jr (1971) Glucose and lipid homeostasis in the absence of human growth hormone. Journal of Clinical Investigation 50, 574–582.CrossRefGoogle ScholarPubMed
Mrosovsky, N (1976) Lipid programs and life strategies in hibernators. American Zoologist 16, 685–697.CrossRefGoogle Scholar
Okada, T, Kawano, Y, Sakakibara, T, Hazeki, O & Ui, M (1994) Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin. Journal of Biological Chemistry 269, 3568–3573.CrossRefGoogle ScholarPubMed
Paz, K, Hemi, R, LeRoith, D, Karasik, A, Elhanany, E, Kanety, H & Zick, Y (1997) A Molecular Basis for Insulin Resistance. Journal of Biological Chemistry 272, 29911–29918.CrossRefGoogle ScholarPubMed
Pelleymounter, MA, Cullen, MJ, Baker, MB, Hecht, R, Winters, D, Boone, T & Collins, F (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540–543.CrossRefGoogle ScholarPubMed
Peraldi, P, Hotamisligil, GS, Buurman, WA, White, MF & Spiegelman, BM (1996) Tumor necrosis factor (TNF)-alpha inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase. Journal of Biological Chemistry 271, 13018–13022.CrossRefGoogle ScholarPubMed
Rasmussen, MH, Hvidberg, A, Juul, A, Main, KM, Gotfredsen, A, Skakkebaek, NE, Hilsted, J & Skakkebaek, NE (1995) Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. Journal of Clinical Endocrinology and Metabolism 80, 1407–1415.Google ScholarPubMed
Renier, G, Gaudreau, P, Hajjad, H, Deslauriers, N, Houde-Nadeau, M & Brazeau, P (1990) Decreased pituitary growth hormone response to growth hormone-releasing factor in cafeteria-fed rats: dietary and obesity effects. Neuroendocrinology 52, 284–290.CrossRefGoogle ScholarPubMed
Richelsen, B, Pedersen, SB, Borglum, JD, Moller-Pedersen, T, Jorgensen, J & Jorgensen, JO (1994) Growth hormone treatment of obese women for 5 wk: effect on body composition and adipose tissue LPL activity. American Journal of Physiology 266, E211–E216.Google ScholarPubMed
Rosenbaum, M, Nicolson, M, Hirsch, J, Murphy, E, Chu, F & Leibel, RL (1996) Effects of gender, body composition, and menopause on plasma concentrations of leptin. Journal of Clinical Endocrinology and Metabolism 81, 3424–3427.Google ScholarPubMed
Saad, MJ, Araki, E, Miralpeix, M, Rothenberg, PL, White, MF & Kahn, CR (1992) Regulation of insulin receptor substrate-1 in liver and muscle of animal models of insulin resistance. Journal of Clinical Investigation 90, 1839–1849.CrossRefGoogle ScholarPubMed
Sakaue, H, Hara, K, Noguchi, T, Matozaki, T, Kotani, K, Ogawa, W, Yonezawa, K, Waterfield, MD & Kasuga, M (1995) Ras-independent and wortmannin-sensitive activation of glycogen synthase by insulin in Chinese hamster ovary cells. Journal of Biological Chemistry 270, 11304–11309.CrossRefGoogle ScholarPubMed
Saladin, R, De Vos, P, Guerre-Millo, M, Leturque, A, Girard, J, Staels, B & Auwerx, J (1995) Transient increase in obese gene expression after food intake or insulin administration. Nature 377, 527–529.CrossRefGoogle ScholarPubMed
Salomon, F, Cuneo, RC, Hesp, R & Sonksen, PH (1989) The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. New England Journal of Medicine 321, 1797–1803.CrossRefGoogle ScholarPubMed
Schwartz, MW, Peskind, E, Raskind, M, Boyko, EJ & Porte, D (1996) Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nature Medicine 2, 589–593.CrossRefGoogle ScholarPubMed
Shepherd, PR, Nave, BT & Siddle, K (1995) Insulin activates glycogen synthase by a novel PI 3-kinase/p70s6k dependent pathway in 3T3-L1 adipocytes. Biochemical Society Transactions. 23, 202S.CrossRefGoogle ScholarPubMed
Snyder, DK, Clemmons, DR & Underwood, LE (1988) Treatment of obese, diet-restricted subjects with growth hormone for 11 weeks: effects on anabolism, lipolysis, and body composition. Journal of Clinical Endocrinology and Metabolism 67, 54–61.CrossRefGoogle ScholarPubMed
Sun, XJ, Crimmins, DL, Myers, MG Jr, Miralpeix, M & White, MF (1993) Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1. Molecular and Cellular Biology 13, 7418–7428.Google ScholarPubMed
Sun, XJ, Wang, LM, Zhang, Y, Yenush, L, Myers, MG Jr, Glasheen, E, Lane, WS, Pierce, JH & White, MF (1995) Role of IRS-2 in insulin and cytokine signalling. Nature 377, 173–177.CrossRefGoogle ScholarPubMed
Sutherland, C, O'Brien, RM & Granner, DK (1995) Phosphatidylinositol 3-kinase, but not p70/p85 ribosomal S6 protein kinase, is required for the regulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression by insulin. Dissociation of signaling pathways for insulin and phorbol ester regulation of PEPCK gene expression. Journal of Biological Chemistry 270, 15501–15506.CrossRefGoogle Scholar
Takahashi, J, Furuhata, Y, Ikeda, A, Takahashi, M, Iwata, H, Kazusaka, A & Fujita, S (1999) Characterization of hepatic cytochrome P450 isozyme composition in the transgenic rat expressing low level human growth hormone. Xenobiotica 29, 1203–1212.CrossRefGoogle ScholarPubMed
Tartaglia, LA, Dembski, M, Weng, X, Deng, N, Culpepper, J, Devos, R, Richards, GJ, Campfield, LA, Clark, FT & Deeds, J (1995) Identification and expression cloning of a leptin receptor, OB-R. Cell 83, 1263–1271.CrossRefGoogle ScholarPubMed
Thirone, AC, Carvalho, CR & Saad, MJ (1999) Growth hormone stimulates the tyrosine kinase activity of JAK2 and induces tyrosine phosphorylation of insulin receptor substrates and Shc in rat tissues. Endocrinology 140, 55–62.CrossRefGoogle ScholarPubMed
Tojo, H, Tanaka, S, Matsuzawa, A, Takahashi, M & Tachi, C (1993) Production and characterization of transgenic mice expressing a hGH fusion gene driven by the promoter of mouse whey acidic protein (mWAP) putatively specific to mammary gland. Journal of Reproducion and Development 39, 145–155.CrossRefGoogle Scholar
Trayhurn, P, Hoggard, N, Mercer, JG & Rayner, DV (1999) Leptin: fundamental aspects. International Journal of Obesity and Related Metabolic Disorders 23, 22–28.CrossRefGoogle ScholarPubMed
Turner, ND, Knapp, JR, Byers, FM & Kopchick, JJ (1998) Expression of mutant bovine growth hormone genes in mice perturbs age-related nutrient utilization patterns. Journal of Nutrition 128, 520–524.CrossRefGoogle ScholarPubMed
Veldhuis, JD, Iranmanesh, A, Ho, KK, Waters, MJ, Johnson, ML & Lizarralde, G (1991) Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man. Journal of Clinical Endocrinology and Metabolism 72, 51–59.CrossRefGoogle ScholarPubMed
Vigneri, R, Pliam, NB, Cohen, DC, Pezzino, V, Wong, KY & Goldfine, ID (1978) In vivo regulation of cell surface and intracellular insulin binding sites by insulin. Journal of Biological Chemistry 253, 8192–8197.CrossRefGoogle ScholarPubMed
Virkamaki, A, Ueki, K & Kahn, CR (1999) Protein-protein interaction in insulin signaling and the molecular mechanisms of insulin resistance. Journal of Clinical Investigations 103, 931–943.CrossRefGoogle ScholarPubMed
Wolfsdorf, JI, Sadeghi-Nejad, A & Senior, B (1983) Hypoketonemia and age-related fasting hypoglycemia in growth hormone deficiency. Metabolism: Clinical and Experimental 32, 457–462.CrossRefGoogle ScholarPubMed
Wu-Peng, XS, Chua, SC Jr, Okada, N, Liu, SM, Nicolson, M & Leibel, RL (1997) Phenotype of the obese Koletsky (f) rat due to Tyr793stop mutation in the extracellular domain of the leptin receptor (Lepr). Diabetes 46, 513–518.CrossRefGoogle ScholarPubMed
Yamauchi, T, Kaburagi, Y, Ueki, K, Tsuji, Y, Stark, GR, Kerr, IM, Tsushima, T, Akanuma, Y, Komuro, I, Tobe, K, Yazaki, Y & Kadowaki, T (1998) Growth hormone and prolactin stimulate tyrosine phosphorylation of insulin receptor substrate-1, -2, and -3, their association with p85 phosphatidylinositol 3-kinase (PI3-kinase), and concomitantly PI3-kinase activation via JAK2 kinase. Journal of Biological Chemistry 273, 15719–15726.CrossRefGoogle ScholarPubMed
Yip, RG & Goodman, HM (1999) Growth hormone and dexamethasone stimulate lipolysis and activate adenylyl cyclase in rat adipocytes by selectively shifting Gi alpha2 to lower density membrane fractions. Endocrinology 140, 1219–1227.CrossRefGoogle ScholarPubMed
Young, RA (1976) Fat, energy, and mammalian survival. American Zoologist 16, 699–710.CrossRefGoogle Scholar
Zhang, Y, Proenca, R, Maffei, M, Barone, M, Leopold, L & Friedman, JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432.CrossRefGoogle ScholarPubMed