Table of Contents Author Guidelines Submit a Manuscript
Experimental Diabetes Research
Volume 2008, Article ID 176245, 8 pages
http://dx.doi.org/10.1155/2008/176245
Review Article

Role of C-Peptide in the Regulation of Microvascular Blood Flow

1Medical Department, Institute for Clinical Research and Development, 55116 Mainz, Germany
2Department of Endocrinolgy and Metabolism, Johannes Gutenberg University, 55131 Mainz, Germany
3Diabetes Centre, 13187 Berlin, Germany

Received 29 November 2007; Accepted 23 June 2008

Academic Editor: George King

Copyright © 2008 T. Forst et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. W. Steffes, S. Sibley, M. Jackson, and W. Thomas, “β-cell function and the development of diabetes-related complications in the diabetes control and complications trial,” Diabetes Care, vol. 26, no. 3, pp. 832–836, 2003. View at Publisher · View at Google Scholar
  2. R. Scognamiglio, C. Negut, S. V. De Kreutzenberg, A. Tiengo, and A. Avogaro, “Postprandial myocardial perfusion in healthy subjects and in type 2 diabetic patients,” Circulation, vol. 112, no. 2, pp. 179–184, 2005. View at Publisher · View at Google Scholar
  3. T. Forst, S. Forst, K. Strunk et al., “Impact of insulin on microvascular blood flow and endothelial cell function in the postprandial state in patients with type 1 diabetes,” Journal of Diabetes and Its Complications, vol. 19, no. 3, pp. 128–132, 2005. View at Publisher · View at Google Scholar
  4. E. Tibiriçá, E. Rodrigues, R. A. Cobas, and M. B. Gomes, “Endothelial function in patients with type 1 diabetes evaluated by skin capillary recruitment,” Microvascular Research, vol. 73, no. 2, pp. 107–112, 2007. View at Publisher · View at Google Scholar
  5. T. Forst, A. Pfützner, T. Kunt et al., “Skin microcirculation in patients with type I diabetes with and without neuropathy after neurovascular stimulation,” Clinical Science, vol. 94, no. 3, pp. 255–261, 1998. View at Google Scholar
  6. T. Kunt, T. Forst, O. Harzer et al., “The influence of advanced glycation endproducts (AGE) on the expression of human endothelial adhesion molecules,” Experimental and Clinical Endocrinology and Diabetes, vol. 106, no. 3, pp. 183–188, 1998. View at Google Scholar
  7. E. Ernst and A. Matrai, “Altered red and white blood cell rheology in type II diabetes,” Diabetes, vol. 35, no. 12, pp. 1412–1415, 1986. View at Publisher · View at Google Scholar
  8. A. J. Barnes, P. Locke, P. R. Scudder, T. L. Dormandy, J. A. Dormandy, and J. Slack, “Is hyperviscosity a treatable component of diabetic microcirculatory disease?” The Lancet, vol. 2, no. 8042, pp. 789–791, 1977. View at Publisher · View at Google Scholar
  9. P. Finotti and P. Palatini, “Reduction of erythrocyte (Na+-K+)ATPase activity in type 1 (insulin-dependent) diabetic subjects and its activation by homologous plasma,” Diabetologia, vol. 29, no. 9, pp. 623–628, 1986. View at Publisher · View at Google Scholar
  10. D. E. McMillan, N. G. Utterback, and J. La Puma, “Reduced erythrocyte deformability in diabetes,” Diabetes, vol. 27, no. 9, pp. 895–901, 1978. View at Google Scholar
  11. J. E. Tooke, “Microvascular function in human diabetes: a physiological perspective,” Diabetes, vol. 44, no. 7, pp. 721–726, 1995. View at Publisher · View at Google Scholar
  12. J. Calles-Escandon and M. Cipolla, “Diabetes and endothelial dysfunction: a clinical perspective,” Endocrine Reviews, vol. 22, no. 1, pp. 36–52, 2001. View at Publisher · View at Google Scholar
  13. L. Kuo, M. J. Davis, and W. M. Chilian, “Myogenic activity in isolated subepicardial and subendocardial coronary arterioles,” American Journal of Physiology, vol. 255, no. 6, pp. H1558–H1562, 1988. View at Google Scholar
  14. J. A. Colwell and M. F. Lopes-Virella, “A review of the development of large-vessel disease in diabetes mellitus,” American Journal of Medicine, vol. 85, no. 5, supplement 1, pp. 113–118, 1988. View at Publisher · View at Google Scholar
  15. R. F. Furchgott and J. V. Zawadzki, “The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine,” Nature, vol. 288, no. 5789, pp. 373–376, 1980. View at Publisher · View at Google Scholar
  16. R. M. J. Palmer, A. G. Ferrige, and S. Moncada, “Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor,” Nature, vol. 327, no. 6122, pp. 524–526, 1987. View at Publisher · View at Google Scholar
  17. S. J. Morris, A. C. Shore, and J. E. Tooke, “Responses of the skin microcirculation to acetylcholine and sodium nitroprusside in patients with NIDDM,” Diabetologia, vol. 38, no. 11, pp. 1337–1344, 1995. View at Publisher · View at Google Scholar
  18. G. M. Pieper, W. Siebeneich, G. Moore-Milton, and A. M. Roza, “Reversal by L-arginine of a dysfunctional arginine/nitric oxide pathway in the endothelium of the genetic diabetic BB rat,” Diabetologia, vol. 40, no. 8, pp. 910–915, 1997. View at Publisher · View at Google Scholar
  19. P. G. McNally, P. A. C. Watt, T. Rimmer, A. C. Burden, J. R. Hearnshaw, and H. Thurston, “Impaired contraction and endothelium-dependent relaxation in isolated resistance vessels from patients with insulin-dependent diabetes mellitus,” Clinical Science, vol. 87, no. 1, pp. 31–36, 1994. View at Google Scholar
  20. M. T. Johnstone, S. J. Creager, K. M. Scales, J. A. Cusco, B. K. Lee, and M. A. Creager, “Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus,” Circulation, vol. 88, no. 6, pp. 2510–2516, 1993. View at Google Scholar
  21. T. Wallerath, T. Kunt, T. Forst et al., “Stimulation of endothelial nitric oxide synthase by proinsulin C-peptide,” Nitric Oxide, vol. 9, no. 2, pp. 95–102, 2003. View at Publisher · View at Google Scholar
  22. T. Kunt, S. Schneider, A. Pfützner et al., “The effect of human proinsulin C-peptide on erythrocyte deformability in patients with type I diabetes mellitus,” Diabetologia, vol. 42, no. 4, pp. 465–471, 1999. View at Publisher · View at Google Scholar
  23. U. Förstermann, J. S. Pollock, H. H. Schmidt, M. Heller, and F. Murad, “Calmodulin-dependent endothelium-derived relaxing factor/nitric oxide synthase activity is present in the particulate and cytosolic fractions of bovine aortic endothelial cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 5, pp. 1788–1792, 1991. View at Publisher · View at Google Scholar
  24. U. Förstermann, A. Mugge, U. Alheid, A. Haverich, and J. C. Frolich, “Selective attenuation of endothelium-mediated vasodilation in atherosclerotic human coronary arteries,” Circulation Research, vol. 62, no. 2, pp. 185–190, 1988. View at Google Scholar
  25. T. Kitamura, K. Kimura, B. D. Jung et al., “Proinsulin C-peptide activates cAMP response element-binding proteins through the p38 mitogen-activated protein kinase pathway in mouse lung capillary endothelial cells,” Biochemical Journal, vol. 366, no. 3, pp. 737–744, 2002. View at Publisher · View at Google Scholar
  26. H. Wald, P. Scherzer, R. Rasch, and M. M. Popovtzer, “Renal tubular Na+-K+-ATPase in diabetes mellitus: relationship to metabolic abnormality,” American Journal of Physiology, vol. 265, no. 1, pp. E96–E101, 1993. View at Google Scholar
  27. A. Gerbi, O. Barbey, D. Raccah et al., “Alteration of Na,K-ATPase isoenzymes in diabetic cardiomyopathy: effect of dietary supplementation with fish oil (n-3 fatty acids) in rats,” Diabetologia, vol. 40, no. 5, 505 pages, 1997. View at Publisher · View at Google Scholar
  28. P. Vague, D. Dufayet, T. Coste, C. Moriscot, M. F. Jannot, and D. Raccah, “Association of diabetic neuropathy with Na/K ATPase gene polymorphism,” Diabetologia, vol. 40, no. 5, pp. 506–511, 1997. View at Publisher · View at Google Scholar
  29. D. A. Simmons, E. F. Kern, A. I. Winegrad, and D. B. Martin, “Basal phosphatidylinositol turnover controls aortic Na+/K+ ATPase activity,” The Journal of Clinical Investigation, vol. 77, no. 2, pp. 503–513, 1986. View at Publisher · View at Google Scholar
  30. A. M. Rose and R. Valdes Jr., “Understanding the sodium pump and its relevance to disease,” Clinical Chemistry, vol. 40, no. 9, pp. 1674–1685, 1994. View at Google Scholar
  31. R. M. Rapoport, K. Schwartz, and F. Murad, “Effects of Na+,K+-pump inhibitors and membrane depolarizing agents on acetylcholine-induced endothelium-dependent relaxation and cyclic GMP accumulation in rat aorta,” European Journal of Pharmacology, vol. 110, no. 2, pp. 203–209, 1985. View at Publisher · View at Google Scholar
  32. C. J. J. Tack, J. A. Lutterman, G. Vervoort, T. Thien, and P. Smits, “Activation of the sodium-potassium pump contributes to insulin-induced vasodilation in humans,” Hypertension, vol. 28, no. 3, pp. 426–432, 1996. View at Google Scholar
  33. S. Gupta, C. McArthur, C. Grady, and N. B. Ruderman, “Stimulation of vascular Na+-K+-ATPase activity by nitric oxide: a cGMP-independent effect,” American Journal of Physiology, vol. 266, no. 5, pp. H2146–H2151, 1994. View at Google Scholar
  34. V. E. Rand and C. J. Garland, “Endothelium-dependent relaxation to acetylcholine in the rabbit basilar artery: importance of membrane hyperpolarization,” British Journal of Pharmacology, vol. 106, no. 1, pp. 143–150, 1992. View at Google Scholar
  35. Y. Ohtomo, A. Aperia, B. Sahlgren, B.-L. Johansson, and J. Wahren, “C-peptide stimulates rat renal tubular Na+,K+-ATPase activity in synergism with neuropeptide Y,” Diabetologia, vol. 39, no. 2, pp. 199–205, 1996. View at Publisher · View at Google Scholar
  36. Y. Ohtomo, T. Bergman, B.-L. Johansson, H. Jörnvall, and J. Wahren, “Differential effects of proinsulin C-peptide fragments on Na+,K+-ATPase activity of renal tubule segments,” Diabetologia, vol. 41, no. 3, pp. 287–291, 1998. View at Publisher · View at Google Scholar
  37. A. Djemli-Shipkolye, P. Gallice, T. Coste et al., “The effects ex vivo and in vitro of insulin and C-peptide on Na/K adenosine triphosphatase activity in red blood cell membranes of type 1 diabetic patients,” Metabolism, vol. 49, no. 7, pp. 868–872, 2000. View at Publisher · View at Google Scholar
  38. T. Forst, D. Dufayet De La Tour, T. Kunt et al., “Effects of proinsulin C-peptide on nitric oxide, microvascular blood flow and erythrocyte Na+,K+-ATPase activity in diabetes mellitus type I,” Clinical Science, vol. 98, no. 3, pp. 283–290, 2000. View at Publisher · View at Google Scholar
  39. S. Chien, “Red cell deformability and its relevance to blood flow,” Annual Review of Physiology, vol. 49, pp. 177–192, 1987. View at Publisher · View at Google Scholar
  40. D. Bareford, P. E. Jennings, P. C. Stone, S. Baar, A. H. Barnett, and J. Stuart, “Effects of hyperglycaemia and sorbitol accumulation on erythrocyte deformability in diabetes mellitus,” Journal of Clinical Pathology, vol. 39, no. 7, pp. 722–727, 1986. View at Publisher · View at Google Scholar
  41. K. Chimori, S. Miyazaki, J. Kosaka, A. Sakanaka, Y. Yasuda, and K. Miura, “Increased sodium influx into erythrocytes in diabetes mellitus and hypertension,” Clinical and Experimental Hypertension, vol. 8, no. 2, pp. 185–199, 1986. View at Publisher · View at Google Scholar
  42. N. S. Cohen, J. E. Ekholm, M. G. Luthra, and D. J. Hanahan, “Biochemical characterization of density separated human erythrocytes,” Biochimica et Biophysica Acta, vol. 419, no. 2, pp. 229–242, 1976. View at Publisher · View at Google Scholar
  43. Y. Baba, M. Kai, T. Kamada, S. Setoyama, and S. Otsuji, “Higher levels of erythrocyte membrane microviscosity in diabetes,” Diabetes, vol. 28, no. 12, pp. 1138–1140, 1979. View at Publisher · View at Google Scholar
  44. H. Schmid-Schönbein and E. Volger, “Red-cell aggregation and red-cell deformability in diabetes,” Diabetes, vol. 25, supplement 2, pp. 897–902, 1976. View at Google Scholar
  45. L. Mazzanti, R. A. Rabini, E. Faloia, P. Fumelli, E. Bertoil, and R. De Pirro, “Altered cellular Ca2+ and Na+ transport in diabetes mellitus,” Diabetes, vol. 39, no. 7, pp. 850–854, 1990. View at Publisher · View at Google Scholar
  46. Y. Takakuwa and N. Mohandas, “Modulation of erythrocyte membrane material properties by Ca2+ and calmodulin. Implications for their role in regulation of skeletal protein interactions,” The Journal of Clinical Investigation, vol. 82, no. 2, pp. 394–400, 1988. View at Publisher · View at Google Scholar
  47. P. O. Schischmanoff, R. Winardi, D. E. Discher et al., “Defining of the minimal domain of protein 4.1 involved in spectrin-actin binding,” Journal of Biological Chemistry, vol. 270, no. 36, pp. 21243–21250, 1995. View at Publisher · View at Google Scholar
  48. K. Gardner and V. Bennett, “A new erythrocyte membrane-associated protein with calmodulin binding activity. Identification and purification,” Journal of Biological Chemistry, vol. 261, no. 3, pp. 1339–1348, 1986. View at Google Scholar
  49. M. A. Cotter, K. Ekberg, J. Wahren, and N. E. Cameron, “Effects of proinsulin C-peptide in experimental diabetic neuropathy: vascular actions and modulation by nitric oxide synthase inhibition,” Diabetes, vol. 52, no. 7, pp. 1812–1817, 2003. View at Publisher · View at Google Scholar
  50. H. Kamiya, W. Zhang, K. Ekberg, J. Wahren, and A. A. F. Sima, “C-peptide reverses nociceptive neuropathy in type 1 diabetes,” Diabetes, vol. 55, no. 12, pp. 3581–3587, 2006. View at Publisher · View at Google Scholar
  51. B.-L. Johansson, K. Borg, E. Fernqvist-Forbes, A. Kernell, T. Odergren, and J. Wahren, “Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with type 1 diabetes mellitus,” Diabetic Medicine, vol. 17, no. 3, pp. 181–189, 2000. View at Publisher · View at Google Scholar
  52. K. Ekberg, L. Juntti-Berggren, A. Norrby et al., “C-peptide improves sensory nerve function in type 1 diabetes and neuropathy,” Diabetologia, vol. 48, supplement 1, p. A81, 2005. View at Google Scholar
  53. K. Lindström, C. Johansson, E. Johnsson, and B. Haraldsson, “Acute effects of C-peptide on the microvasculature of isolated perfused skeletal muscles and kidneys in rat,” Acta Physiologica Scandinavica, vol. 156, no. 1, pp. 19–25, 1996. View at Publisher · View at Google Scholar
  54. M. E. Jensen and E. J. Messina, “C-peptide induces a concentration-dependent dilation of skeletal muscle arterioles only in presence of insulin,” American Journal of Physiology, vol. 276, no. 4 45-4, pp. H1223–H1228, 1999. View at Google Scholar
  55. Y. Ido, A. Vindigni, K. Chang et al., “Prevention of vascular and neural dysfunction in diabetic rats by C-peptide,” Science, vol. 277, no. 5325, pp. 563–566, 1997. View at Publisher · View at Google Scholar
  56. B.-L. Johansson, B. Linde, and J. Wahren, “Effects of C-peptide on blood flow, capillary diffusion capacity and glucose utilization in the exercising forearm of type 1 (insulin-dependent) diabetic patients,” Diabetologia, vol. 35, no. 12, pp. 1151–1158, 1992. View at Publisher · View at Google Scholar
  57. J. E. Tooke, P. E. Lins, J. Ostergren, and B. Fagrell, “Skin microvascular autoregulatory responses in type I diabetes: the influence of duration and control,” International Journal of Microcirculation, Clinical and Experimental, vol. 4, no. 3, pp. 249–256, 1985. View at Google Scholar
  58. U. Ewald, T. Tuvemo, and G. Rooth, “Early reduction of vascular reactivity in diabetic children detected by transcutaneous oxygen electrode,” The Lancet, vol. 1, no. 8233, pp. 1287–1288, 1981. View at Publisher · View at Google Scholar
  59. M. D. Flynn and J. E. Tooke, “Aetiology of diabetic foot ulceration: a role for the microcirculation?” Diabetic Medicine, vol. 9, no. 4, pp. 320–329, 1992. View at Google Scholar
  60. G. Jörneskog, K. Brismar, and B. Fagrell, “Skin capillary circulation is more impaired in the toes of diabetic than non-diabetic patients with peripheral vascular disease,” Diabetic Medicine, vol. 12, no. 1, pp. 36–41, 1995. View at Google Scholar
  61. G. Jörneskog, K. Brismar, and B. Fagrell, “Skin capillary circulation severely impaired in toes of patients with IDDM, with and without late diabetic complications,” Diabetologia, vol. 38, no. 4, pp. 474–480, 1995. View at Publisher · View at Google Scholar
  62. A. J. M. Boulton, J. H. B. Scarpello, and J. D. Ward, “Venous oxygenation in the diabetic neuropathic foot: evidence of arteriovenous shunting?” Diabetologia, vol. 22, no. 1, pp. 6–8, 1982. View at Publisher · View at Google Scholar
  63. G. Jörneskog, J. Ostergren, G. Tyden, J. Bolinder, and B. Fagrell, “Does combined kidney and pancreas transplantation reverse functional diabetic microangiopathy?” Transplant International, vol. 3, no. 3, pp. 167–170, 1990. View at Google Scholar
  64. T. Forst, T. Kunt, T. Pohlmann et al., “Biological activity of C-peptide on the skin microcirculation in patients with insulin-dependent diabetes mellitus,” The Journal of Clinical Investigation, vol. 101, no. 10, pp. 2036–2041, 1998. View at Publisher · View at Google Scholar
  65. E. Fernqvist-Forbes, B.-L. Johansson, and M. J. Eriksson, “Effects of C-peptide on forearm blood flow and brachial artery dilatation in patients with type 1 diabetes mellitus,” Acta Physiologica Scandinavica, vol. 172, no. 3, pp. 159–165, 2001. View at Publisher · View at Google Scholar
  66. E. Polska, J. Kolodjaschna, F. Berisha et al., “C-peptide does not affect ocular blood flow in patients with type 1 diabetes,” Diabetes Care, vol. 29, no. 9, pp. 2034–2038, 2006. View at Publisher · View at Google Scholar
  67. R. Rigler, A. Pramanik, P. Jonasson et al., “Specific binding of proinsulin C-peptide to human cell membranes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 23, pp. 13318–13323, 1999. View at Publisher · View at Google Scholar