PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
 
J Clin Invest. 1992 June; 89(6): 1908–1913.
PMCID: PMC295890

Effects of insulin-like growth factor-I on glucose tolerance, insulin levels, and insulin secretion.

Abstract

Insulin-like growth factor-I (IGF-I) and insulin interact with related receptors to lower plasma glucose and to exert mitogenic effects. Recombinant human IGF-I (rhIGF-I) was recently shown to decrease serum levels of insulin and C-peptide in fasted normal subjects without affecting plasma glucose levels. In this study we have investigated in six healthy volunteers the responses of glucose, insulin, and C-peptide levels to intravenous rhIGF-I infusions (7 and 14 micrograms/kg.h) during standard oral glucose tolerance tests (oGTT) and meal tolerance tests (MTT), respectively. Glucose tolerance remained unchanged during the rhIGF-I infusions in the face of lowered insulin and C-peptide levels. The decreased insulin/glucose-ratio presumably is caused by an enhanced tissue sensitivity to insulin. The lowered area under the insulin curve during oGTT and MTT as a result of the administration of rhIGF-I were related to the fasting insulin levels during saline infusion (oGTT: r = 0.825, P less than 0.05; MTT: r = 0.895, P less than 0.02). RhIGF-I, however, did not alter the ratio between C-peptide and insulin, suggesting that the metabolic clearance of endogenous insulin remained unchanged. In conclusion, rhIGF-I increased glucose disposal and directly suppressed insulin secretion. RhIGF-I probably increased insulin sensitivity as a result of decreased insulin levels and suppressed growth hormone secretion. RhIGF-I, therefore, may be therapeutically useful in insulin resistance of type 2 diabetes, obesity, and hyperlipidemia.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Poggi C, Le Marchand-Brustel Y, Zapf J, Froesch ER, Freychet P. Effects and binding of insulin-like growth factor I in the isolated soleus muscle of lean and obese mice: comparison with insulin. Endocrinology. 1979 Sep;105(3):723–730. [PubMed]
  • Yu KT, Czech MP. The type I insulin-like growth factor receptor mediates the rapid effects of multiplication-stimulating activity on membrane transport systems in rat soleus muscle. J Biol Chem. 1984 Mar 10;259(5):3090–3095. [PubMed]
  • Dohm GL, Elton CW, Raju MS, Mooney ND, DiMarchi R, Pories WJ, Flickinger EG, Atkinson SM, Jr, Caro JF. IGF-I--stimulated glucose transport in human skeletal muscle and IGF-I resistance in obesity and NIDDM. Diabetes. 1990 Sep;39(9):1028–1032. [PubMed]
  • King GL, Kahn CR, Rechler MM, Nissley SP. Direct demonstration of separate receptors for growth and metabolic activities of insulin and multiplication-stimulating activity (an insulinlike growth factor) using antibodies to the insulin receptor. J Clin Invest. 1980 Jul;66(1):130–140. [PMC free article] [PubMed]
  • Sinha MK, Buchanan C, Leggett N, Martin L, Khazanie PG, Dimarchi R, Pories WJ, Caro JF. Mechanism of IGF-I-stimulated glucose transport in human adipocytes. Demonstration of specific IGF-I receptors not involved in stimulation of glucose transport. Diabetes. 1989 Oct;38(10):1217–1225. [PubMed]
  • Caro JF, Poulos J, Ittoop O, Pories WJ, Flickinger EG, Sinha MK. Insulin-like growth factor I binding in hepatocytes from human liver, human hepatoma, and normal, regenerating, and fetal rat liver. J Clin Invest. 1988 Apr;81(4):976–981. [PMC free article] [PubMed]
  • Zapf J, Hauri C, Waldvogel M, Froesch ER. Acute metabolic effects and half-lives of intravenously administered insulinlike growth factors I and II in normal and hypophysectomized rats. J Clin Invest. 1986 Jun;77(6):1768–1775. [PMC free article] [PubMed]
  • Zenobi PD, Guler HP, Zapf J, Froesch ER. Insulin-like growth factors in the Göttinger miniature-pig. Acta Endocrinol (Copenh) 1988 Mar;117(3):343–352. [PubMed]
  • Jacob R, Barrett E, Plewe G, Fagin KD, Sherwin RS. Acute effects of insulin-like growth factor I on glucose and amino acid metabolism in the awake fasted rat. Comparison with insulin. J Clin Invest. 1989 May;83(5):1717–1723. [PMC free article] [PubMed]
  • Giacca A, Gupta R, Efendic S, Hall K, Skottner A, Lickley L, Vranic M. Differential effects of IGF-I and insulin on glucoregulation and fat metabolism in depancreatized dogs. Diabetes. 1990 Mar;39(3):340–347. [PubMed]
  • Guler HP, Zapf J, Froesch ER. Short-term metabolic effects of recombinant human insulin-like growth factor I in healthy adults. N Engl J Med. 1987 Jul 16;317(3):137–140. [PubMed]
  • Rossetti L, Frontoni S, Dimarchi R, DeFronzo RA, Giaccari A. Metabolic effects of IGF-I in diabetic rats. Diabetes. 1991 Apr;40(4):444–448. [PubMed]
  • Jacob RJ, Sherwin RS, Bowen L, Fryburg D, Fagin KD, Tamborlane WV, Shulman GI. Metabolic effects of IGF-I and insulin in spontaneously diabetic BB/w rats. Am J Physiol. 1991 Feb;260(2 Pt 1):E262–E268. [PubMed]
  • Schoenle E, Zapf J, Humbel RE, Froesch ER. Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature. 1982 Mar 18;296(5854):252–253. [PubMed]
  • Scheiwiller E, Guler HP, Merryweather J, Scandella C, Maerki W, Zapf J, Froesch ER. Growth restoration of insulin-deficient diabetic rats by recombinant human insulin-like growth factor I. Nature. 1986 Sep 11;323(6084):169–171. [PubMed]
  • Guler HP, Schmid C, Zapf J, Froesch ER. Effects of recombinant insulin-like growth factor I on insulin secretion and renal function in normal human subjects. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2868–2872. [PubMed]
  • Van Schravendijk CF, Foriers A, Van den Brande JL, Pipeleers DG. Evidence for the presence of type I insulin-like growth factor receptors on rat pancreatic A and B cells. Endocrinology. 1987 Nov;121(5):1784–1788. [PubMed]
  • Sönksen PH, Greenwood FC, Ellis JP, Lowy C, Rutherford A, Nabarro JD. Changes of carbohydrate tolerance in acromegaly with progress of the disease and in response to treatment. J Clin Endocrinol Metab. 1967 Oct;27(10):1418–1430. [PubMed]
  • Luft R, Cerasi E, Hamberger CA. Studies on the pathogenesis of diabetes in acromegaly. Acta Endocrinol (Copenh) 1967 Dec;56(4):593–607. [PubMed]
  • UNGER RH, EISENTRAUT AM, MADISON LL. The effects of total starvation upon the levels of circulating glucagon and insulin in man. J Clin Invest. 1963 Jul;42:1031–1039. [PMC free article] [PubMed]
  • Cahill GF, Jr, Herrera MG, Morgan AP, Soeldner JS, Steinke J, Levy PL, Reichard GA, Jr, Kipnis DM. Hormone-fuel interrelationships during fasting. J Clin Invest. 1966 Nov;45(11):1751–1769. [PMC free article] [PubMed]
  • DeFronzo RA, Soman V, Sherwin RS, Hendler R, Felig P. Insulin binding to monocytes and insulin action in human obesity, starvation, and refeeding. J Clin Invest. 1978 Jul;62(1):204–213. [PMC free article] [PubMed]
  • Newman WP, Brodows RG. Insulin action during acute starvation: evidence for selective insulin resistance in normal man. Metabolism. 1983 Jun;32(6):590–596. [PubMed]
  • Zapf J, Walter H, Froesch ER. Radioimmunological determination of insulinlike growth factors I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia. J Clin Invest. 1981 Nov;68(5):1321–1330. [PMC free article] [PubMed]
  • Zapf J, Schmid C, Guler HP, Waldvogel M, Hauri C, Futo E, Hossenlopp P, Binoux M, Froesch ER. Regulation of binding proteins for insulin-like growth factors (IGF) in humans. Increased expression of IGF binding protein 2 during IGF I treatment of healthy adults and in patients with extrapancreatic tumor hypoglycemia. J Clin Invest. 1990 Sep;86(3):952–961. [PMC free article] [PubMed]
  • Feek CM, Bevan JS, Taylor S, Brown NS, Baird JD. The effect of bromocriptine on insulin secretion and glucose tolerance in patients with acromegaly. Clin Endocrinol (Oxf) 1981 Nov;15(5):473–478. [PubMed]
  • Guler HP, Zapf J, Schmid C, Froesch ER. Insulin-like growth factors I and II in healthy man. Estimations of half-lives and production rates. Acta Endocrinol (Copenh) 1989 Dec;121(6):753–758. [PubMed]
  • Copeland KC, Underwood LE, Van Wyk JJ. Induction of immunoreactive somatomedin C human serum by growth hormone: dose-response relationships and effect on chromatographic profiles. J Clin Endocrinol Metab. 1980 Apr;50(4):690–697. [PubMed]
  • Baxter RC, Martin JL. Radioimmunoassay of growth hormone-dependent insulinlike growth factor binding protein in human plasma. J Clin Invest. 1986 Dec;78(6):1504–1512. [PMC free article] [PubMed]
  • Hardouin S, Gourmelen M, Noguiez P, Seurin D, Roghani M, Le Bouc Y, Povoa G, Merimee TJ, Hossenlopp P, Binoux M. Molecular forms of serum insulin-like growth factor (IGF)-binding proteins in man: relationships with growth hormone and IGFs and physiological significance. J Clin Endocrinol Metab. 1989 Dec;69(6):1291–1301. [PubMed]
  • White RM, Nissley SP, Moses AC, Rechler MM, Johnsonbaugh RE. The growth hormone dependence of a somatomedin-binding protein in human serum. J Clin Endocrinol Metab. 1981 Jul;53(1):49–57. [PubMed]
  • Suikkari AM, Koivisto VA, Rutanen EM, Yki-Järvinen H, Karonen SL, Seppälä M. Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. J Clin Endocrinol Metab. 1988 Feb;66(2):266–272. [PubMed]
  • Yeoh SI, Baxter RC. Metabolic regulation of the growth hormone independent insulin-like growth factor binding protein in human plasma. Acta Endocrinol (Copenh) 1988 Dec;119(4):465–473. [PubMed]
  • Suikkari AM, Koivisto VA, Koistinen R, Seppälä M, Yki-Järvinen H. Dose-response characteristics for suppression of low molecular weight plasma insulin-like growth factor-binding protein by insulin. J Clin Endocrinol Metab. 1989 Jan;68(1):135–140. [PubMed]
  • Snyder DK, Clemmons DR. Insulin-dependent regulation of insulin-like growth factor-binding protein-1. J Clin Endocrinol Metab. 1990 Dec;71(6):1632–1636. [PubMed]
  • Bar RS, Clemmons DR, Boes M, Busby WH, Booth BA, Dake BL, Sandra A. Transcapillary permeability and subendothelial distribution of endothelial and amniotic fluid insulin-like growth factor binding proteins in the rat heart. Endocrinology. 1990 Sep;127(3):1078–1086. [PubMed]
  • Van Schravendijk CF, Heylen L, Van den Brande JL, Pipeleers DG. Direct effect of insulin and insulin-like growth factor-I on the secretory activity of rat pancreatic beta cells. Diabetologia. 1990 Nov;33(11):649–653. [PubMed]
  • Leahy JL, Vandekerkhove KM. Insulin-like growth factor-I at physiological concentrations is a potent inhibitor of insulin secretion. Endocrinology. 1990 Mar;126(3):1593–1598. [PubMed]
  • Archer JA, Gorden P, Roth J. Defect in insulin binding to receptors in obese man. Amelioration with calorie restriction. J Clin Invest. 1975 Jan;55(1):166–174. [PMC free article] [PubMed]
  • Bar RS, Harrison LC, Muggeo M, Gorden P, Kahn CR, Roth J. Regulation of insulin receptors in normal and abnormal physiology in humans. Adv Intern Med. 1979;24:23–52. [PubMed]
  • Henry RR, Wallace P, Olefsky JM. Effects of weight loss on mechanisms of hyperglycemia in obese non-insulin-dependent diabetes mellitus. Diabetes. 1986 Sep;35(9):990–998. [PubMed]
  • Walker JL, Ginalska-Malinowska M, Romer TE, Pucilowska JB, Underwood LE. Effects of the infusion of insulin-like growth factor I in a child with growth hormone insensitivity syndrome (Laron dwarfism). N Engl J Med. 1991 May 23;324(21):1483–1488. [PubMed]
  • Takano K, Hizuka N, Shizume K, Asakawa K, Fukuda I, Demura H. Repeated sc administration of recombinant human insulin-like growth factor I (IGF-I) to human subjects for 7 days. Growth Regul. 1991 Mar;1(1):23–28. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation