Treatments in Endocrinology

, Volume 1, Issue 6, pp 399–410

Therapeutic Potential of Insulin-Like Growth Factor-1 in Patients with Diabetes Mellitus

Review Article

Abstract

Insulin-like growth factor-1 (IGF-1) and its receptors share considerable homology with insulin and insulin receptors, and their respective signaling pathways interact at the post receptor level. while the growth hormone (GH)-IGF-1 axis principally regulates tissue growth and differentiation, insulin exerts it primary effects on fuel metabolism. However, these two endocrine systems interact at multiple levels and in diabetes mellitus the GH-IGF-1 axis is grossly disturbed, with increased secretion of GH, reduced plasma levels of IGF-1, and complex tissue-specific changes in IGF binding proteins (IGFBPs). These observations have given rise to the view that GH-IGF-1 axis dysfunction, particularly low plasma levels of circulating IGF-1, probably play a significant role in several aspects of the pathophysiology of diabetes mellitus, including insulin resistance and poor glycemic control, and may also influence the development of microvascular complications.

The availability of recombinant human IGF-1 (rhIGF-1; mecasermin), used either alone or in combination with insulin, has led to experimental studies and clinical trials in humans testing these hypotheses. These studies have examined the impact of subcutaneous rhIGF-1 injections on sensitivity and metabolic parameters. In patients with type 1 and 2 diabetes mellitus, insulin sensitivity is significantly improved, insulin requirements are reduced, and glycemic control of dyslipidemia is generally improved in short-term studies. rhIGF-1 is a particularly attractive possibility in patients with type 2 diabetes mellitus, where insulin resistance is the fundamental problem. Some patients with genetic syndromes of severe insulin resistance also benefit from treatment with rhIGF-1, which can bypass blocks in the insulin signaling pathway. The common adverse effects reported for rhIGF-1 are dose-related and include edema, jaw pain, arthralgia, myalgia, hypotension, injection site pain, and less commonly, Bell’s palsy and raised intracranial pressure.

Although disturbance of the GH-IGF-1 axis participates in the development of diabetic complications, the functional consequences of the complex changes in IGFBP expression at the tissue level are uncertain, and it is not known whether systemic IGF-1 therapy or other manipulations of the GH-IGF-1 axis would be helpful or harmful. Experimentally, IGF-1 has a protective effect on neuropathy, and could find an application in the healing of neuropathic ulcers. The potential benefits of IGF-1 therapy in diabetes mellitus have yet to be realised.

References

  1. 1.
    Ferry Jr RJ, Cerri RW, Cohen P. Insulin-like growth factor binding proteins: new proteins, new functions. Horm Res 1999; 51: 53–67PubMedCrossRefGoogle Scholar
  2. 2.
    Schmid C. Insulin-like growth factors. Cell Biol Int 1995; 19:445–57PubMedCrossRefGoogle Scholar
  3. 3.
    Binoux M. The IGF system in metabolism regulation. Diabetes Metab 1995; 21: 330–7Google Scholar
  4. 4.
    Kalloo-Hosein HE, Whitehead JP, Soos M, et al. Differential signaling to glycogen synthesis by the intracellular domain of the insulin versus the insulin-like growth factor-1 receptor: evidence from studies of TrkC-chimeras. J Biol Chem 1997; 272: 24325–32PubMedCrossRefGoogle Scholar
  5. 5.
    Kadowaki T, Tobe K, Honda-Yamamoto R, et al. Signal transduction mechanism of insulin and insulin-like growth factor-1. Endocr J 1996; 43: S33–41PubMedCrossRefGoogle Scholar
  6. 6.
    Withers DJ, Burks DJ, Towery HH, et al. IRS-2 coordinates IGF-1 receptor-mediated beta-cell development and peripheral insulin signalling. Nat Genet 1999; 23: 32–40PubMedGoogle Scholar
  7. 7.
    Inoue S, Fukuda K, Kudara T, et al. Augmented growth response to IGF-1 via increased IRS-1 in Chinese hamster ovary cells expressing kinase-negative insulin receptors. Diabetologia 1999; 42: 763–72PubMedCrossRefGoogle Scholar
  8. 8.
    Conover CA. Regulation and physiological role of insulin-like growth factor binding proteins. Endocr J 1996; 43: S43–8PubMedCrossRefGoogle Scholar
  9. 9.
    Shimasaki S, Ling N. Identification and molecular characterization of insulin-like growth factor binding proteins (IGFBP-1, -2, -3, -4, -5 and -6). Prog Growth Factor Res 1991; 3: 243–66PubMedCrossRefGoogle Scholar
  10. 10.
    Holden JP, Butzow TL, Laughlin GA, et al. Regulation of insulin-like growth factor binding protein-1 during the 24-hour metabolic clock and in response to hypoinsulinemia induced by fasting and Sandostatin in normal women. J Soc Gynecol Investig 1995; 2: 38–44PubMedCrossRefGoogle Scholar
  11. 11.
    Ogilvy-Stuart AL, Hands SJ, Adcock CJ, et al. Insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-1, growth hormone, and feeding in the newborn. J Clin Endocrinol Metab 1998; 83: 3550–7PubMedCrossRefGoogle Scholar
  12. 12.
    Hilding A, Brismar K, Degerblad M, et al. Altered relation between circulating levels of insulin-like growth factor-binding protein-1 and insulin in growth hormone-deficient patients and insulin-dependent diabetic patients compared to that in healthy subjects. J Clin Endocrinol Metab 1995; 80: 2646–52PubMedCrossRefGoogle Scholar
  13. 13.
    Norrelund H, Fisker S, Vahl N, et al. Evidence supporting a direct suppressive effect of growth hormone on serum IGFBP-1 levels: experimental studies in normal, obese and GH-deficient adults. Growth Horm IGF Res 1999; 9: 52–60PubMedCrossRefGoogle Scholar
  14. 14.
    Lu X, Shi Z, Murphy LJ. Growth hormone suppression of insulin-like growth factor binding protein-1 promoter activity. Mol Cell Endocrinol 1999; 149: 19–28PubMedCrossRefGoogle Scholar
  15. 15.
    Bereket A, Lang CH, Blethen SL, et al. Insulin-like growth factor-binding protein-2 and insulin: studies in children with type 1 diabetes mellitus and maturity-onset diabetes of the young. J Clin Endocrinol Metab 1995; 80: 3647–52PubMedCrossRefGoogle Scholar
  16. 16.
    Zapf J, Schmid C, Guler HP, et al. 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; 86: 952–61PubMedCrossRefGoogle Scholar
  17. 17.
    Clemmons DR. Insulin-like growth factor binding proteins and their role in controlling IGF actions. Cytokine Growth Factor Rev 1997; 8: 45–62PubMedCrossRefGoogle Scholar
  18. 18.
    Wu HB, Lee CY, Rechler MM. Proteolysis of insulin-like growth factor binding protein-3 in serum from pregnant, non-pregnant and fetal rats by matrix metalloproteinases and serine proteases. Horm Metab Res 1999; 31: 186–91PubMedCrossRefGoogle Scholar
  19. 19.
    Rees C, Clemmons DR, Horvitz GD, et al. A protease-resistant form of insulin-like growth factor (IGF) binding protein 4 inhibits IGF-1 actions. Endocrinology 1998; 139: 4182–8PubMedCrossRefGoogle Scholar
  20. 20.
    Bach LA, Thotakura NR, Rechler MM. Human insulin-like growth factor binding protein-6 is O-glycosylated. Growth Regul 1993; 3: 59–62PubMedGoogle Scholar
  21. 21.
    Jehle PM, Mohan S. The mechanism by which IGFBP-5 exerts anabolic effects in bone. Kidney Int 2000; 57: 1209–10PubMedCrossRefGoogle Scholar
  22. 22.
    Fainstein-Day P, Fagin JA, Vaglio RM, et al. Growth hormone-insulin-like growth factor-I axis in adult insulin-dependent diabetic patients: evidence for central hypersensitivity to growth hormone-releasing hormone and peripheral resistance to growth hormone. Horm Metab Res 1998; 30: 737–42PubMedCrossRefGoogle Scholar
  23. 23.
    Mohamed-Ali V, Pinkney JH, Panahloo A, et al. Insulin-like growth factor binding protein-1 in NIDDM: relationship with the insulin resistance syndrome. Clin Endocrinol Oxf 1999; 50: 221–8PubMedCrossRefGoogle Scholar
  24. 24.
    Shishko PI, Dreval AV, Abugova IA, et al. Insulin-like growth factors and binding proteins in patients with recent-onset type 1 (insulin-dependent) diabetes mellitus: influence of diabetes control and intraportal insulin infusion. Diabetes Res Clin Pract 1994; 25: 1–12PubMedCrossRefGoogle Scholar
  25. 25.
    Bach MA, Chin E, Bondy CA. The effects of subcutaneous insulin-like growth factor-I infusion in insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1994; 79: 1040–5PubMedCrossRefGoogle Scholar
  26. 26.
    Cheetham TD, Jones J, Taylor AM, et al. The effects of recombinant insulin-like growth factor I administration on growth hormone levels and insulin requirements in adolescents with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1993; 36: 678–81PubMedCrossRefGoogle Scholar
  27. 27.
    Quattrin T, Thrailkill K, Baker L, et al. Dual hormonal replacement with insulin and recombinant human insulin-like growth factor I in IDDM: effects on glycemic control, IGF-I levels, and safety profile. Diabetes Care 1997; 20: 374–80PubMedCrossRefGoogle Scholar
  28. 28.
    Thrailkill K, Quattrin T, Baker L, et al. Dual hormonal replacement therapy with insulin and recombinant human insulin-like growth factor (IGF)-I in insulin-dependent diabetes mellitus: effects on the growth hormone/IGF/IGF-binding protein system. J Clin Endocrinol Metab 1997; 82: 1181–7PubMedCrossRefGoogle Scholar
  29. 29.
    Carroll PV, Umpleby M, Alexander EL, et al. Recombinant human insulin-like growth factor-I (rhIGF-I) therapy in adults with type 1 diabetes mellitus: effects on IGFs, IGF-binding proteins, glucose levels and insulin treatment. Clin Endocrinol (Oxf) 1998; 49: 739–46CrossRefGoogle Scholar
  30. 30.
    Thrailkill K, Quattrin T, Baker L, et al. Co-therapy with recombinant human insulin-like growth factor-1 and insulin improves glycaemic control in type 1 diabetes. Diabetes Care 1999; 22: 585–92PubMedCrossRefGoogle Scholar
  31. 31.
    Acerini CL, Patton CM, Savage MO, et al. Randomised placebo-controlled trial of human recombinant insulin-like growth factor I plus intensive insulin therapy in adolescents with insulin-dependent diabetes mellitus. Lancet 1997; 350: 1199–204PubMedCrossRefGoogle Scholar
  32. 32.
    Zenobi PD, Holzmann P, Glatz Y, et al. Improvement of lipid profile in type 2 (non-insulin-dependent) diabetes mellitus by insulin-like growth factor I. Diabetologia 1993; 36: 465–9PubMedCrossRefGoogle Scholar
  33. 33.
    Zenobi PD, Jaeggi-Groisman SE, Riesen WF, et al. Insulin-like growth factor-I improves glucose and lipid metabolism in type 2 diabetes mellitus. J Clin Invest 1992; 90: 2234–41PubMedCrossRefGoogle Scholar
  34. 34.
    Schalch DS, Turman NJ, Marcsisin VS, et al. Short-term effects of recombinant human insulin-like growth factor I on metabolic control of patients with type II diabetes mellitus. J Clin Endocrinol Metab 1993; 77: 1563–8PubMedCrossRefGoogle Scholar
  35. 35.
    Jabri N, Schalch DS, Schwartz SL, et al. Adverse effects of recombinant human insulin-like growth factor I in obese insulin-resistant type II diabetic patients. Diabetes 1994; 43: 369–74PubMedCrossRefGoogle Scholar
  36. 36.
    Moses AC, Young SC, Morrow LA, et al. Recombinant human insulin-like growth factor I increases insulin sensitivity and improves glycemic control in type II diabetes. Diabetes 1996; 45: 91–100PubMedCrossRefGoogle Scholar
  37. 37.
    Radetti G, Paganini C, Antoniazzi F, et al. Growth hormone-binding proteins, IGF-I and IGF-binding proteins in children and adolescents with type 1 diabetes mellitus. Horm Res 1997; 47: 110–5PubMedCrossRefGoogle Scholar
  38. 38.
    Edge JA, Matthews DR, Dunger DB. The dawn phenomenon is related to overnight growth hormone release in adolescent diabetics. Clin Endocrinol (Oxf) 1990; 33: 729–37CrossRefGoogle Scholar
  39. 39.
    Mercado M, Molitch ME, Baumann G. Low plasma growth hormone binding protein in IDDM. Diabetes 1992; 41: 605–9PubMedCrossRefGoogle Scholar
  40. 40.
    Menon RK, Arslanian S, May B, et al. Diminished growth hormone-binding protein in children with insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1992; 74: 934–8PubMedCrossRefGoogle Scholar
  41. 41.
    Holl RW, Siegler B, Scherbaum WA, et al. The serum growth hormone-binding protein is reduced in young patients with insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1993; 76: 165–7PubMedCrossRefGoogle Scholar
  42. 42.
    Batch JA, Baxter RC, Werther G. Abnormal regulation of insulin-like growth factor binding proteins in adolescents with insulin-dependent diabetes. J Clin Endocrinol Metab 1991; 73: 964–8PubMedCrossRefGoogle Scholar
  43. 43.
    Shishko PI, Dreval AV, Abugova IA, et al. Insulin-like growth factors and binding proteins in patients with recent-onset type 1 (insulin-dependent) diabetes mellitus: influence of diabetes control and intraportal insulin infusion. Diabetes Res Clin Pract 1994; 25: 1–12PubMedCrossRefGoogle Scholar
  44. 44.
    Bereket A, Lang CH, Blethen SL, et al. Insulin-like growth factor binding protein-3 proteolysis in children with insulin-dependent diabetes mellitus: a possible role for insulin in the regulation of IGFBP-3 protease activity. J Clin Endocrinol Metab 1995; 80: 2282–8PubMedCrossRefGoogle Scholar
  45. 45.
    Cheetham TD, Taylor A, Holly JM, et al. The effects of recombinant human insulin-like growth factor-I (IGF-I) administration on the levels of IGF-I, IGF-II and IGF-binding proteins in adolescents with insulin-dependent diabetes mellitus. J Endocrinol 1994; 142: 367–74PubMedCrossRefGoogle Scholar
  46. 46.
    Carroll PV, Christ ER, Umpleby AM, et al. IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp. Diabetes 2000; 49: 789–96PubMedCrossRefGoogle Scholar
  47. 47.
    Granberry MC, Fonseca VA. Insulin resistance syndrome: options for treatment. South Med J 1999; 92: 2–15PubMedCrossRefGoogle Scholar
  48. 48.
    Froesch ER, Zenobi PD, Hussain M. Metabolic and therapeutic effects of insulin-like growth factor I. Horm Res 1994; 42: 66–71PubMedCrossRefGoogle Scholar
  49. 49.
    Zenobi PD, Graf S, Ursprung H, et al. Effects of insulin-like growth factor-I on glucose tolerance, insulin levels, and insulin secretion. J Clin Invest 1992; 89: 1908–13PubMedCrossRefGoogle Scholar
  50. 50.
    Porksen N, Hussain MA, Bianda TL, et al. IGF-I inhibits burst mass of pulsatile insulin secretion at supraphysiological and low IGF-I infusion rates. Am J Physiol 1997; 272: E352–8PubMedGoogle Scholar
  51. 51.
    Hussain MA, Schmitz O, Mengel A, et al. Insulin-like growth factor I stimulates lipid oxidation, reduces protein oxidation, and enhances insulin sensitivity in humans. J Clin Invest 1993; 92: 2249–56PubMedCrossRefGoogle Scholar
  52. 52.
    Donath MY, Jenni R, Brunner HP, et al. Cardiovascular and metabolic effects of insulin-like growth factor I at rest and during exercise in humans. J Clin Endocrinol Metab 1996; 81: 4089–94PubMedCrossRefGoogle Scholar
  53. 53.
    Bianda TL, Hussain MA, Keller A, et al. Insulin-like growth factor-I in man enhances lipid mobilization and oxidation induced by a growth hormone pulse. Diabetologia 1996; 39: 961–9PubMedCrossRefGoogle Scholar
  54. 54.
    Hussain MA, Schmitz O, Mengel A, et al. Comparison of the effects of growth hormone and insulin-like growth factor I on substrate oxidation and on insulin sensitivity in growth hormone-deficient humans. J Clin Invest 1994; 94: 1126–33PubMedCrossRefGoogle Scholar
  55. 55.
    Janssen JA, Lamberts SW. The role of IGF-I in the development of cardiovascular disease in type 2 diabetes mellitus: is prevention possible? Eur J Endocrinol 2002; 146: 467–77PubMedCrossRefGoogle Scholar
  56. 56.
    RhIGF-1 in NIDDM Study (RINDS) Group. Evidence from a dose ranging study that recombinant insulin-like growth factor 1 (rhIGF-1) effectively and safely improves glycaemic control in non-insilin dependent diabetes mellitus (NIDDM). Diabetes 1996; 45 Suppl. 2: 27AGoogle Scholar
  57. 57.
    Clemmons DR, Moses AC, McKay MJ, et al. The combination of insulin-like growth factor I and insulin-like growth factor-binding protein-3 reduces insulin requirements in insulin-dependent type 1 diabetes: evidence for in vivo biological activity. J Clin Endocrinol Metab 2000; 85: 1518–24PubMedCrossRefGoogle Scholar
  58. 58.
    Moses AC. Treatment of diabetes mellitus with IGF-l/IGFBP-3. 83rd Annual meeting of the Endocrine Society; 2001 Jun 20–23; Denver (CO)Google Scholar
  59. 59.
    Ishihama H, Suzuki Y, Muramatsu K, et al. Long-term follow up in type A insulin resistant syndrome treated by insulin-like growth factor I. Arch Dis Child 1994; 71: 144–6PubMedCrossRefGoogle Scholar
  60. 60.
    Bondy CA, Underwood LE, Clemmons DR, et al. Clinical uses of insulin-like growth factor I. Ann Intern Med 1994; 120: 593–601PubMedGoogle Scholar
  61. 61.
    Schoenle EJ, Zenobi PD, Torresani T, et al. Recombinant human insulin-like growth factor I (rhIGF I) reduces hyperglycaemia in patients with extreme insulin resistance. Diabetologia 1991; 34: 675–9PubMedCrossRefGoogle Scholar
  62. 62.
    Zenobi PD, Glatz Y, Keller A, et al. Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A. Eur J Endocrinol 1994; 131: 251–7PubMedCrossRefGoogle Scholar
  63. 63.
    Kuzuya H, Matsuura N, Sakamoto M, et al. Trial of insulinlike growth factor I therapy for patients with extreme insulin resistance syndromes. Diabetes 1993; 42: 696–705PubMedCrossRefGoogle Scholar
  64. 64.
    Vestergaard H, Rossen M, Urhammer SA, et al. Short- and long-term metabolic effects of recombinant human IGF-I treatment in patients with severe insulin resistance and diabetes mellitus. Eur J Endocrinol 1997; 136: 475–82PubMedCrossRefGoogle Scholar
  65. 65.
    Longo N, Singh R, Griffin LD, et al. Impaired growth in Rabson-Mendenhall syndrome: lack of effect of growth hormone and insulin-like growth factor-I. J Clin Endocrinol Metab 1994; 79: 799–805PubMedCrossRefGoogle Scholar
  66. 66.
    Backeljauw PF, Alves C, Eidson M, et al. Effect of intravenous insulin-like growth factor I in two patients with leprechaunism. Pediatr Res 1994; 36: 749–54PubMedCrossRefGoogle Scholar
  67. 67.
    Nakae J, Kato M, Murashita M, et al. Long-term effect of recombinant human insulin-like growth factor I on metabolic and growth control in a patient with leprechaunism. J Clin Endocrinol Metab 1998; 83: 542–9PubMedCrossRefGoogle Scholar
  68. 68.
    Lundbaek K, Christensen NJ, Jensen VA, et al. Diabetes, diabetic angiopathy, and growth hormone. Lancet 1970; II: 131–3CrossRefGoogle Scholar
  69. 69.
    Poulsen JE. Diabetes and anterior pituitary insufficiency: final course and postmortem study of a diabetic patient with Sheehan’s syndrome. Diabetes 1966; 15: 73–7PubMedGoogle Scholar
  70. 70.
    Wright AD, Kohner EM, Oakley NW, et al. Serum growth hormone levels and the response of diabetic retinopathy to pituitary ablation. BMJ 1969; 2: 346–8PubMedCrossRefGoogle Scholar
  71. 71.
    Lundbaek K. Growth hormone’s role in diabetic microangiopathy. Diabetes 1976; 25: 845–9PubMedGoogle Scholar
  72. 72.
    Merimee TJ. A follow-up study of vascular disease in growth-hormone-deficient dwarfs with diabetes. N Engl J Med 1978; 298: 1217–22PubMedCrossRefGoogle Scholar
  73. 73.
    Sato K, Ikeda T, Miki T, et al. Somatomedin-C and diabetic retinopathy. Jpn J Ophthalmol 1988; 32: 219–22PubMedGoogle Scholar
  74. 74.
    Lamberton RP, Goodman AD, Kassoff A, et al. Von Willebrand factor (VIII R:Ag), fibronectin, and insulin-like growth factors I and II in diabetic retinopathy and nephropathy. Diabetes 1984; 33: 125–9PubMedCrossRefGoogle Scholar
  75. 75.
    Hyer SL, Sharp PS, Brooks RA, et al. Serum IGF-1 concentration in diabetic retinopathy. Diabet Med 1988; 5: 356–60PubMedCrossRefGoogle Scholar
  76. 76.
    Nardelli GM, Guastamacchia E, Di-Paolo S, et al. Somatomedin-C (SM-C). Study in diabetic patients with and without retinopathy. Acta Diabetol Lat 1989; 26: 217–24PubMedCrossRefGoogle Scholar
  77. 77.
    Dills DG, Moss SE, Klein R, et al. Is insulinlike growth factor I associated with diabetic retinopathy? Diabetes 1990; 39: 191–5PubMedCrossRefGoogle Scholar
  78. 78.
    Dills DG, Moss SE, Klein R, et al. Association of elevated IGF-I levels with increased retinopathy in late-onset diabetes. Diabetes 1991; 40: 1725–30PubMedCrossRefGoogle Scholar
  79. 79.
    Arner P, Sjoberg S, Gjotterberg M, et al. Circulating insulin-like growth factor I in type 1 (insulin-dependent) diabetic patients with retinopathy. Diabetologia 1989; 32: 753–8PubMedCrossRefGoogle Scholar
  80. 80.
    Grant M, Russell B, Fitzgerald C, et al. Insulin-like growth factors in vitreous: studies in control and diabetic subjects with neovascularization. Diabetes 1986; 35: 416–20PubMedCrossRefGoogle Scholar
  81. 81.
    Grant M, Jerdan J, Merimee TJ. Insulin-like growth factor-I modulates endothelial cell chemotaxis.J Clin Endocrinol Metab 1987; 65: 370–1PubMedCrossRefGoogle Scholar
  82. 82.
    Waldbillig RJ, Jones BE, Schoen TJ, et al. Vitreal insulin-like growth factor binding proteins (IGFBPs) are increased in human and animal diabetics. Curr Eye Res 1994; 13: 539–46PubMedCrossRefGoogle Scholar
  83. 83.
    Pfeiffer A, Spranger J, Meyer-Schwickerath R, et al. Growth factor alterations in advanced diabetic retinopathy: a possible role of blood retina barrier breakdown. Diabetes 1997; 46: S26–30PubMedGoogle Scholar
  84. 84.
    Janssen JA, Lamberts SW. Circulating IGF-I and its protective role in the pathogenesis of diabetic angiopathy. Clin Endocrinol (Oxf) 2000; 52: 1–9CrossRefGoogle Scholar
  85. 85.
    Flyvbjerg A. Role of growth hormone, insulin-like growth factors (IGFs) and IGF-binding proteins in the renal complications of diabetes. Kidney Int Suppl 1997; 60: S12–9PubMedGoogle Scholar
  86. 86.
    Flyvbjerg A, Bornfeldt KE, Orskov H, et al. Effect of insulin-like growth factor I infusion on renal hypertrophy in experimental diabetes mellitus in rats. Diabetologia 1991; 34: 715–20PubMedCrossRefGoogle Scholar
  87. 87.
    Flyvbjerg A, Orskov H. Kidney tissue insulin-like growth factor I and initial renal growth in diabetic rats: relation to severity of diabetes. Acta Endocrinol (Copenh) 1990; 122: 374–8Google Scholar
  88. 88.
    Landau D, Chin E, Bondy C, et al. Expression of insulin-like growth factor binding proteins in the rat kidney: effects of long-term diabetes. Endocrinology 1995; 136: 1835–42PubMedCrossRefGoogle Scholar
  89. 89.
    Gronbaek H, Nielsen B, Frystyk J, et al. Effect of lanreotide on local kidney IGF-I and renal growth in experimental diabetes in the rat. Exp Nephrol 1996; 4: 295–303PubMedGoogle Scholar
  90. 90.
    Flyvbjerg A, Frystyk J, Thorlacius-Ussing O, et al. Somatostatin analogue administration prevents increase in kidney somatomedin C and initial renal growth in diabetic and uninephrectomized rats. Diabetologia 1989; 32: 261–5PubMedCrossRefGoogle Scholar
  91. 91.
    Flyvbjerg A, Marshall SM, Frystyk J, et al. Octreotide administration in diabetic rats: effects on renal hypertrophy and urinary albumin excretion. Kidney Int 1992; 41: 805–12PubMedCrossRefGoogle Scholar
  92. 92.
    Vora J, Owens DR, Luzio S, et al. Renal response to intravenous somatostatin in insulin-dependent diabetic patients and normal subjects. J Clin Endocrinol Metab 1987; 64: 975–9PubMedCrossRefGoogle Scholar
  93. 93.
    Pedersen MM, Christensen SE, Christiansen JS, et al. Acute effects of a somatostatin analogue on kidney function in type 1 diabetic patients. Diabet Med 1990; 7: 304–9PubMedCrossRefGoogle Scholar
  94. 94.
    Serri O, Beauregard H, Brazeau P, et al. Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin-dependent diabetes. JAMA 1991; 265: 888–92PubMedCrossRefGoogle Scholar
  95. 95.
    Hansen AP. Normalization of growth hormone hyperresponse to exercise in juvenile diabetics after “normalization” of blood sugar. J Clin Invest 1971; 50: 1806–11PubMedCrossRefGoogle Scholar
  96. 96.
    Andersen AR, Christiansen JS, Andersen JK, et al. Diabetic nephropathy in Type 1 (insulin-dependent) diabetes: an epidemiological study. Diabetologia 1983; 25: 496–501PubMedCrossRefGoogle Scholar
  97. 97.
    Lunetta M, Di-Mauro M, Le-Moli R, et al. Effect of octreotide on growth hormone, IGF-I, IGFBP-3, glucagon, cortisol and epinephrine response to insulin-induced hypoglycaemia in insulin-dependent diabetic patients. Diabetes Metab 1997; 23: 524–7PubMedGoogle Scholar
  98. 98.
    Lee PE, Meneilly GS. The effect of octreotide on glucose and insulin levels in a patient with type 2 diabetes on glibenclamide. Diabetes Metab 1999; 25: 347–9PubMedGoogle Scholar
  99. 99.
    Tomlinson DR. Future prevention and treatment of diabetic neuropathy. Diabetes Metab 1998; 24: 79–83PubMedGoogle Scholar
  100. 100.
    Apfel SC. Neurotrophic factors in the therapy of diabetic neuropathy. Am J Med 1999; 107: 34S–42SPubMedCrossRefGoogle Scholar
  101. 101.
    Crosby SR, Tsigos C, Anderton CD, et al. Elevated plasma insulin-like growth factor binding protein-1 levels in type 1 (insulin-dependent) diabetic patients with peripheral neuropathy. Diabetologia 1992; 35: 868–72PubMedCrossRefGoogle Scholar
  102. 102.
    Ishii DN. Implication of insulin-like growth factors in the pathogenesis of diabetic neuropathy. Brain Res Brain Res Rev 1995; 20: 47–67PubMedCrossRefGoogle Scholar
  103. 103.
    Ishii DN, Guertin DM, Whalen LR. Reduced insulin-like growth factor-I mRNA content in liver, adrenal glands and spinal cord of diabetic rats. Diabetologia 1994; 37: 1073–81PubMedCrossRefGoogle Scholar
  104. 104.
    Bitar MS, Pilcher CW, Khan I, et al. Diabetes-induced suppression of IGF-1 and its receptor mRNA levels in rat superior cervical ganglia. Diabetes Res Clin Pract 1997; 38: 73–80PubMedCrossRefGoogle Scholar
  105. 105.
    Russell JW, Sullivan KA, Windebank AJ, et al. Neurons undergo apoptosis in animal and cell culture models of diabetes. Neurobiol Dis 1999; 6: 347–63PubMedCrossRefGoogle Scholar
  106. 106.
    Russell JW, Feldman EL. Insulin-like growth factor-I prevents apoptosis in sympathetic neurons exposed to high glucose. Horm Metab Res 1999; 31: 90–6PubMedCrossRefGoogle Scholar
  107. 107.
    Schmidt RE, Dorsey DA, Beaudet LN, et al. Insulin-like growth factor I reverses experimental diabetic autonomic neuropathy. Am J Pathol 1999; 155: 1651–60PubMedCrossRefGoogle Scholar
  108. 108.
    Zhuang HX, Snyder CK, Pu SF, et al. Insulin-like growth factors reverse or arrest diabetic neuropathy: effects on hyperalgesia and impaired nerve regeneration in rats. Exp Neurol 1996; 140: 198–205PubMedCrossRefGoogle Scholar
  109. 109.
    Zhuang HX, Wuarin L, Fei ZJ, et al. Insulin-like growth factor (IGF) gene expression is reduced in neural tissues and liver from rats with non-insulin-dependent diabetes mellitus, and IGF treatment ameliorates diabetic neuropathy. J Pharmacol Exp Ther 1997; 283: 366–74PubMedGoogle Scholar
  110. 110.
    Robson MC, Mustoe TA, Hunt TK. The future of recombinant growth factors in wound healing. Am J Surg 1998; 176: 80S–2SPubMedCrossRefGoogle Scholar
  111. 111.
    Richard JL, Parer-Richard C, Daures JP, et al. Effect of topical basic fibroblast growth factor on the healing of chronic diabetic neuropathic ulcer of the foot: a pilot, randomized, double-blind, placebo-controlled study. Diabetes Care 1995; 18: 64–9PubMedCrossRefGoogle Scholar
  112. 112.
    Blakytny R, Jude EB, Martin-Gibson J, et al. Lack of insulin-like growth factor 1 (IGF1) in the basal keratinocyte layer of diabetic skin and diabetic foot ulcers. J Pathol 2000; 190: 589–94PubMedCrossRefGoogle Scholar
  113. 113.
    Mitchell P. Cancelled IGF-1 trials bode ill for diabetic patients. Lancet 1997; 350: 1606PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  1. 1.Adipokines and Metabolism Research Group, Institute of Urology, Department of MedicineUniversity College LondonLondonEngland
  2. 2.Diabetes and Endocrinology Research Group, Clinical Science CentreUniversity Hospital AintreeLiverpoolUK

Personalised recommendations