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. 1989 Aug;84(2):619–626. doi: 10.1172/JCI114207

Regulation by fasting of rat insulin-like growth factor I and its receptor. Effects on gene expression and binding.

W L Lowe Jr 1, M Adamo 1, H Werner 1, C T Roberts Jr 1, D LeRoith 1
PMCID: PMC548924  PMID: 2547834

Abstract

We have examined, in liver and extrahepatic tissues, the effects of fasting on total insulin-like growth factor I (IGF-I) mRNA levels, on levels of different IGF-I mRNAs generated by alternative splicing of the primary IGF-I transcript, and on IGF-I receptor binding and mRNA levels. A 48-h fast decreased total IGF-I mRNA levels by approximately 80% in lung and liver, approximately 60% in kidney and muscle, and only approximately 30-40% in stomach, brain, and testes. In heart, IGF-I mRNA levels did not change. The levels of the different splicing variants, however, were essentially coordinately regulated within a given tissue. Specific 125I-IGF-I binding in lung, testes, stomach, kidney, and heart was increased by fasting by approximately 30-100%, whereas in brain 125I-IGF-I binding did not change in response to fasting. In tissues in which fasting increased IGF-I receptor number, receptor mRNA levels increased approximately 1.6- to 2.5-fold, whereas when IGF-I receptor number was unchanged in response to fasting, receptor mRNA levels did not change. These data demonstrate that the change in IGF-I and IGF-I receptor mRNA levels during fasting is quantitatively different in different tissues and suggest that regulation of IGF-I and IGF-I receptor gene expression by fasting is discoordinate.

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Selected References

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  1. Bar R. S., Dake B. L., Stueck S. Stimulation of proteoglycans by IGF I and II in microvessel and large vessel endothelial cells. Am J Physiol. 1987 Jul;253(1 Pt 1):E21–E27. doi: 10.1152/ajpendo.1987.253.1.E21. [DOI] [PubMed] [Google Scholar]
  2. Bell G. I., Stempien M. M., Fong N. M., Rall L. B. Sequences of liver cDNAs encoding two different mouse insulin-like growth factor I precursors. Nucleic Acids Res. 1986 Oct 24;14(20):7873–7882. doi: 10.1093/nar/14.20.7873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cathala G., Savouret J. F., Mendez B., West B. L., Karin M., Martial J. A., Baxter J. D. A method for isolation of intact, translationally active ribonucleic acid. DNA. 1983;2(4):329–335. doi: 10.1089/dna.1983.2.329. [DOI] [PubMed] [Google Scholar]
  4. Clemmons D. R., Han V. K., Elgin R. G., D'Ercole A. J. Alterations in the synthesis of a fibroblast surface associated 35 K protein modulates the binding of somatomedin-C/insulin-like growth factor I. Mol Endocrinol. 1987 May;1(5):339–347. doi: 10.1210/mend-1-5-339. [DOI] [PubMed] [Google Scholar]
  5. Cree T. C., Schalch D. S. Protein utilization in growth: effect of lysine deficiency on serum growth hormone, somatomedins, insulin, total thyroxine (T4) and triiodothyronine, free T4 index, and total corticosterone. Endocrinology. 1985 Aug;117(2):667–673. doi: 10.1210/endo-117-2-667. [DOI] [PubMed] [Google Scholar]
  6. D'Ercole A. J., Stiles A. D., Underwood L. E. Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci U S A. 1984 Feb;81(3):935–939. doi: 10.1073/pnas.81.3.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Emler C. A., Schalch D. S. Nutritionally-induced changes in hepatic insulin-like growth factor I (IGF-I) gene expression in rats. Endocrinology. 1987 Feb;120(2):832–834. doi: 10.1210/endo-120-2-832. [DOI] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  9. Florini J. R., Ewton D. Z., Falen S. L., Van Wyk J. J. Biphasic concentration dependency of stimulation of myoblast differentiation by somatomedins. Am J Physiol. 1986 May;250(5 Pt 1):C771–C778. doi: 10.1152/ajpcell.1986.250.5.C771. [DOI] [PubMed] [Google Scholar]
  10. Froesch E. R., Schmid C., Schwander J., Zapf J. Actions of insulin-like growth factors. Annu Rev Physiol. 1985;47:443–467. doi: 10.1146/annurev.ph.47.030185.002303. [DOI] [PubMed] [Google Scholar]
  11. Havrankova J., Roth J., Brownstein M. J. Concentrations of insulin and insulin receptors in the brain are independent of peripheral insulin levels. Studies of obese and streptozotocin-treated rodents. J Clin Invest. 1979 Aug;64(2):636–642. doi: 10.1172/JCI109504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Havrankova J., Roth J., Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat. Nature. 1978 Apr 27;272(5656):827–829. doi: 10.1038/272827a0. [DOI] [PubMed] [Google Scholar]
  13. Jansen M., van Schaik F. M., Ricker A. T., Bullock B., Woods D. E., Gabbay K. H., Nussbaum A. L., Sussenbach J. S., Van den Brande J. L. Sequence of cDNA encoding human insulin-like growth factor I precursor. Nature. 1983 Dec 8;306(5943):609–611. doi: 10.1038/306609a0. [DOI] [PubMed] [Google Scholar]
  14. Jennische E., Skottner A., Hansson H. A. Dynamic changes in insulin-like growth factor I immunoreactivity correlate to repair events in rat ear after freeze-thaw injury. Exp Mol Pathol. 1987 Oct;47(2):193–201. doi: 10.1016/0014-4800(87)90074-8. [DOI] [PubMed] [Google Scholar]
  15. Jennische E., Skottner A., Hansson H. A. Satellite cells express the trophic factor IGF-I in regenerating skeletal muscle. Acta Physiol Scand. 1987 Jan;129(1):9–15. doi: 10.1111/j.1748-1716.1987.tb08034.x. [DOI] [PubMed] [Google Scholar]
  16. Kasson B. G., Hsueh A. J. Insulin-like growth factor-I augments gonadotropin-stimulated androgen biosynthesis by cultured rat testicular cells. Mol Cell Endocrinol. 1987 Jul;52(1-2):27–34. doi: 10.1016/0303-7207(87)90093-1. [DOI] [PubMed] [Google Scholar]
  17. Lowe W. L., Jr, Lasky S. R., LeRoith D., Roberts C. T., Jr Distribution and regulation of rat insulin-like growth factor I messenger ribonucleic acids encoding alternative carboxyterminal E-peptides: evidence for differential processing and regulation in liver. Mol Endocrinol. 1988 Jun;2(6):528–535. doi: 10.1210/mend-2-6-528. [DOI] [PubMed] [Google Scholar]
  18. Lowe W. L., Jr, Roberts C. T., Jr, Lasky S. R., LeRoith D. Differential expression of alternative 5' untranslated regions in mRNAs encoding rat insulin-like growth factor I. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8946–8950. doi: 10.1073/pnas.84.24.8946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lowe W. L., Jr, Schaffner A. E., Roberts C. T., Jr, LeRoith D. Developmental regulation of somatostatin gene expression in the brain is region specific. Mol Endocrinol. 1987 Feb;1(2):181–187. doi: 10.1210/mend-1-2-181. [DOI] [PubMed] [Google Scholar]
  20. Maes M., Amand Y., Underwood L. E., Maiter D., Ketelslegers J. M. Decreased serum insulin-like growth factor I response to growth hormone in hypophysectomized rats fed a low protein diet: evidence for a postreceptor defect. Acta Endocrinol (Copenh) 1988 Mar;117(3):320–326. doi: 10.1530/acta.0.1170320. [DOI] [PubMed] [Google Scholar]
  21. Meuli C. Effects of insulin and of NSILA-S on the perfused rat heart: glucose uptake, lactate production and efflux of 3-0-methyl glucose. Eur J Clin Invest. 1975 Feb;5(1):93–99. doi: 10.1111/j.1365-2362.1975.tb00433.x. [DOI] [PubMed] [Google Scholar]
  22. Nilsson A., Isgaard J., Lindahl A., Dahlström A., Skottner A., Isaksson O. G. Regulation by growth hormone of number of chondrocytes containing IGF-I in rat growth plate. Science. 1986 Aug 1;233(4763):571–574. doi: 10.1126/science.3523759. [DOI] [PubMed] [Google Scholar]
  23. Pacold S. T., Blackard W. G. Central nervous system insulin receptors in normal and diabetic rats. Endocrinology. 1979 Dec;105(6):1452–1457. doi: 10.1210/endo-105-6-1452. [DOI] [PubMed] [Google Scholar]
  24. Phillips L. S. Nutrition, somatomedins, and the brain. Metabolism. 1986 Jan;35(1):78–87. doi: 10.1016/0026-0495(86)90100-9. [DOI] [PubMed] [Google Scholar]
  25. Phillips L. S., Unterman T. G. Somatomedin activity in disorders of nutrition and metabolism. Clin Endocrinol Metab. 1984 Mar;13(1):145–189. doi: 10.1016/s0300-595x(84)80012-2. [DOI] [PubMed] [Google Scholar]
  26. Roberts C. T., Jr, Lasky S. R., Lowe W. L., Jr, LeRoith D. Rat IGF-I cDNA's contain multiple 5'-untranslated regions. Biochem Biophys Res Commun. 1987 Aug 14;146(3):1154–1159. doi: 10.1016/0006-291x(87)90768-6. [DOI] [PubMed] [Google Scholar]
  27. Roberts C. T., Jr, Lasky S. R., Lowe W. L., Jr, Seaman W. T., LeRoith D. Molecular cloning of rat insulin-like growth factor I complementary deoxyribonucleic acids: differential messenger ribonucleic acid processing and regulation by growth hormone in extrahepatic tissues. Mol Endocrinol. 1987 Mar;1(3):243–248. doi: 10.1210/mend-1-3-243. [DOI] [PubMed] [Google Scholar]
  28. Schalch D. S., Cree T. C. Protein utilization in growth: effect of calorie deficiency on serum growth hormone, somatomedins, total thyroxine (T4) and triiodothyronine, free T4 index, and total corticosterone. Endocrinology. 1985 Dec;117(6):2307–2312. doi: 10.1210/endo-117-6-2307. [DOI] [PubMed] [Google Scholar]
  29. Schlechter N. L., Russell S. M., Spencer E. M., Nicoll C. S. Evidence suggesting that the direct growth-promoting effect of growth hormone on cartilage in vivo is mediated by local production of somatomedin. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7932–7934. doi: 10.1073/pnas.83.20.7932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shimatsu A., Rotwein P. Mosaic evolution of the insulin-like growth factors. Organization, sequence, and expression of the rat insulin-like growth factor I gene. J Biol Chem. 1987 Jun 5;262(16):7894–7900. [PubMed] [Google Scholar]
  31. Shimatsu A., Rotwein P. Sequence of two rat insulin-like growth factor I mRNAs differing within the 5' untranslated region. Nucleic Acids Res. 1987 Sep 11;15(17):7196–7196. doi: 10.1093/nar/15.17.7196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Simon J., Rosebrough R. W., McMurtry J. P., Steele N. C., Roth J., Adamo M., LeRoith D. Fasting and refeeding alter the insulin receptor tyrosine kinase in chicken liver but fail to affect brain insulin receptors. J Biol Chem. 1986 Dec 25;261(36):17081–17088. [PubMed] [Google Scholar]
  33. Smith P. J., Wise L. S., Berkowitz R., Wan C., Rubin C. S. Insulin-like growth factor-I is an essential regulator of the differentiation of 3T3-L1 adipocytes. J Biol Chem. 1988 Jul 5;263(19):9402–9408. [PubMed] [Google Scholar]
  34. Stiles A. D., Sosenko I. R., D'Ercole A. J., Smith B. T. Relation of kidney tissue somatomedin-C/insulin-like growth factor I to postnephrectomy renal growth in the rat. Endocrinology. 1985 Dec;117(6):2397–2401. doi: 10.1210/endo-117-6-2397. [DOI] [PubMed] [Google Scholar]
  35. Ullrich A., Gray A., Tam A. W., Yang-Feng T., Tsubokawa M., Collins C., Henzel W., Le Bon T., Kathuria S., Chen E. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 1986 Oct;5(10):2503–2512. doi: 10.1002/j.1460-2075.1986.tb04528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Underwood L. E., Clemmons D. R., Maes M., D'Ercole A. J., Ketelslegers J. M. Regulation of somatomedin-C/insulin-like growth factor I by nutrients. Horm Res. 1986;24(2-3):166–176. doi: 10.1159/000180556. [DOI] [PubMed] [Google Scholar]
  37. Watanabe N., Rosenfeld R. G., Hintz R. L., Dollar L. A., Smith R. L. Characterization of a specific insulin-like growth factor-I/somatomedin-C receptor on high density, primary monolayer cultures of bovine articular chondrocytes: regulation of receptor concentration by somatomedin, insulin and growth hormone. J Endocrinol. 1985 Nov;107(2):275–283. doi: 10.1677/joe.0.1070275. [DOI] [PubMed] [Google Scholar]

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