C-peptide and its career from innocent bystander to active player in diabetic atherogenesis

Current Atherosclerosis Reports

Volumn 15, Issue 7, 2013, Pages

  Lebherz, Corinna ^a   Marx, Nikolaus ^a  

^a UNIVERSITY HOSPITAL RWTH AACHEN   (Germany)

Author keywords

Atherosclerosis; C peptide; Diabetes; Inflammation; Macrovascular complications; Microvascular complications; Proinsulin

Indexed keywords

ADVANCED GLYCATION END PRODUCT; C PEPTIDE; CD36 ANTIGEN; ENDOTHELIAL NITRIC OXIDE SYNTHASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INSULIN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 10; INTERLEUKIN 8; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MONOCYTE CHEMOTACTIC PROTEIN 1; NITRIC OXIDE; OXIDIZED LOW DENSITY LIPOPROTEIN; PADGEM PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PLACEBO; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; RANTES; REACTIVE OXYGEN METABOLITE; VASCULAR CELL ADHESION MOLECULE 1;

ARTICLE; ATHEROGENESIS; ATHEROSCLEROSIS; AUTONOMIC DYSFUNCTION; BIOACCUMULATION; CALCIUM TRANSPORT; CARDIOVASCULAR MORTALITY; CAUSE OF DEATH; CD4+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL SPECIFICITY; CLINICAL TRIAL (TOPIC); CYTOKINE PRODUCTION; DIABETES MELLITUS; DIABETIC NEPHROPATHY; DIABETIC NEUROPATHY; DISEASE ASSOCIATION; DISEASE MODEL; DOWN REGULATION; DRUG EFFICACY; ENDOTHELIAL DYSFUNCTION; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; FOAM CELL; HUMAN; INFLAMMATION; INSULIN DEPENDENT DIABETES MELLITUS; LEUKOCYTE MIGRATION; MICROALBUMINURIA; MOLECULAR DYNAMICS; MONOCYTE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PROTEIN EXPRESSION; SMOOTH MUSCLE FIBER; TH1 CELL; UPREGULATION; ANIMAL; BLOOD; DIABETIC ANGIOPATHY; HYPERGLYCEMIA; PATHOPHYSIOLOGY; PHYSIOLOGY; VASCULAR ENDOTHELIUM; REVIEW;

ANIMALS; ATHEROSCLEROSIS; C-PEPTIDE; DIABETIC ANGIOPATHIES; DISEASE MODELS, ANIMAL; ENDOTHELIUM, VASCULAR; HUMANS; HYPERGLYCEMIA; INFLAMMATION; NF-KAPPA B;

EID: 84878423596     PISSN: 15233804     EISSN: 15346242     Source Type: Journal    
DOI: 10.1007/s11883-013-0339-3     Document Type: Article

References (54)

1. Wahren J, Ekberg K, Johansson J, et al. Role of C-peptide in human physiology. Am J Physiol Endocrinol Metab. 2000;278:E759-68.
2. Sechi LA, Catena C, Zingaro L, et al. Abnormalities of glucose metabolism in patients with early renal failure. Diabetes. 2002;51:1226-32. (Pubitemid 34438373)
3. Clark JL, Cho S, Rubenstein AH, Steiner DF. Isolation of a proinsulin connecting peptide fragment (C-peptide) from bovine and human pancreas. Biochem Biophys Res Commun. 1969;35:456-61.
4. Johansson J, Ekberg K, Shafqat J, et al. Molecular effects of proinsulin C-peptide. Biochem Biophys Res Commun. 2002;295:1035-40.
5. Ohtomo Y, Bergman T, Johansson BL, et al. Differential effects of proinsulin C-peptide fragments on Na+, K+-ATPase activity of renal tubule segments. Diabetologia. 1998;41:287-91. (Pubitemid 28254822)
6. Ido Y, Vindigni A, Chang K, et al. Prevention of vascular and neural dysfunction in diabetic rats by C-peptide. Science. 1997;277:563-6. (Pubitemid 27369004)
7. Rigler R, Pramanik A, Jonasson P, et al. Specific binding of proinsulin C-peptide to human cell membranes. Proc Natl Acad Sci USA. 1999;96:13318-23.
8. Wang S, Wei W, Zheng Y, et al. The role of insulin C-Peptide in the coevolution analyses of the insulin signaling pathway: a hint for its functions. PLoS One. 2012;7:e52847.
9. Ishii T, Fukano K, Shimada K, et al. Proinsulin C-peptide activates alpha-enolase: implications for C-peptide-cell membrane interaction. J Biochem. 2012;152:53-62.
10. Luppi P, Geng X, Cifarelli V, et al. C-peptide is internalised in human endothelial and vascular smooth muscle cells via early endosomes. Diabetologia. 2009;52:2218-28.
11. Lindahl E, Nyman U, Melles E, et al. Cellular internalization of proinsulin C-peptide. Cell Mol Life Sci. 2007;64:479-86.
12. Candido R, Jandeleit-Dahm KA, Cao Z, et al. Prevention of accelerated atherosclerosis by angiotensin-converting enzyme inhibition in diabetic apolipoprotein E-deficient mice. Circulation. 2002;106:246-53. (Pubitemid 34761307)
13. Gao Y, Lu B, Sun ML, et al. Comparison of atherosclerotic plaque by computed tomography angiography in patients with and without diabetes mellitus and with known or suspected coronary artery disease. Am J Cardiol. 2011;108:809-13.
14. Barlovic DP, Soro-Paavonen A, Jandeleit-Dahm KA. RAGE biology, atherosclerosis and diabetes. Clin Sci. 2011;121:43-55.
15. Walcher D, Marx N. Advanced glycation end products and C-peptide-modulators in diabetic vasculopathy and atherogenesis. Semin Immunopathol. 2009;31:103-11.
16. Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med. 2011;17:1410-22.
17. Rajwani A, Cubbon RM, Wheatcroft SB. Cell-specific insulin resistance: implications for atherosclerosis. Diabetes Metab Res Rev. 2012;28:627-34.
18. Bornfeldt KE, Tabas I. Insulin resistance, hyperglycemia, and atherosclerosis. Cell Metab. 2011;14:575-85.
19. Wallerath T, Kunt T, Forst T, et al. Stimulation of endothelial nitric oxide synthase by proinsulin C-peptide. Nitric Oxide. 2003;9:95-102. (Pubitemid 37386378)
20. Kitamura T, Kimura K, Makondo K, et al. Proinsulin C-peptide increases nitric oxide production by enhancing mitogen-activated protein-kinase-dependent transcription of endothelial nitric oxide synthase in aortic endothelial cells of Wistar rats. Diabetologia. 2003;46:1698-705. (Pubitemid 38005332)
21. Jensen ME, Messina EJ. C-peptide induces a concentration-dependent dilation of skeletal muscle arterioles only in presence of insulin. Am J Physiol. 1999;276:H1223-8.
22. 2+. Diabetes Metab Res Rev. 2013;29:44-52.
23. Haidet J, Cifarelli V, Trucco M, Luppi P. C-peptide reduces pro-inflammatory cytokine secretion in LPS-stimulated U937 monocytes in condition of hyperglycemia. Inflamm Res. 2012;61:27-35.
24. Scalia R, Coyle KM, Levine BJ, et al. C-peptide inhibits leukocyte-endothelium interaction in the microcirculation during acute endothelial dysfunction. FASEB J. 2000;14:2357-64.
25. Walcher D, Aleksic M, Jerg V, et al. C-peptide induces chemotaxis of human CD4-positive cells: involvement of pertussis toxin-sensitive G-proteins and phosphoinositide 3-kinase. Diabetes. 2004;53:1664-70. (Pubitemid 38857022)
26. Marx N, Walcher D, Raichle C, et al. C-peptide colocalizes with macrophages in early arteriosclerotic lesions of diabetic subjects and induces monocyte chemotaxis in vitro. Arterioscler Thromb Vasc Biol. 2004;24:540-5. (Pubitemid 38326150)
27. Aleksic M, Walcher D, Giehl K, et al. Signalling processes involved in C-peptide-induced chemotaxis of CD4-positive lymphocytes. Cell Mol Life Sci. 2009;66:1974-84.
28. Al-Rasheed NM, Chana RS, Baines RJ, et al. Ligand-independent activation of peroxisome proliferator-activated receptor-gamma by insulin and C-peptide in kidney proximal tubular cells: dependent on phosphatidylinositol 3-kinase activity. J Biol Chem. 2004;279:49747-54. (Pubitemid 39577779)
29. Lee SK, Lee JO, Kim JH, et al. C-peptide stimulates nitrites generation via the calcium-JAK2/STAT1 pathway in murine macrophage Raw264.7 cells. Life Sci. 2010;86:863-8.
30. Kitazawa M, Shibata Y, Hashimoto S, et al. Proinsulin C-peptide stimulates a PKC/IkappaB/NF-kappaB signaling pathway to activate COX-2 gene transcription in Swiss 3T3 fibroblasts. J Biochem. 2006;139:1083-8. (Pubitemid 44196885)
31. Luppi P, Cifarelli V, Tse H, et al. Human C-peptide antagonises high glucose-induced endothelial dysfunction through the nuclear factor-kappaB pathway. Diabetologia. 2008;51:1534-43.
32. Cifarelli V, Geng X, Styche A, et al. C-peptide reduces high-glucose-induced apoptosis of endothelial cells and decreases NAD(P)H-oxidase reactive oxygen species generation in human aortic endothelial cells. Diabetologia. 2011;54:2702-12.
33. Kobayashi Y, Naruse K, Hamada Y, et al. Human proinsulin C-peptide prevents proliferation of rat aortic smooth muscle cells cultured in high-glucose conditions. Diabetologia. 2005;48:2396-401. (Pubitemid 41618932)
34. Cifarelli V, Luppi P, Tse HM, et al. Human proinsulin C-peptide reduces high glucose-induced proliferation and NF-kappaB activation in vascular smooth muscle cells. Atherosclerosis. 2008;201:248-57.
35. Walcher D, Babiak C, Poletek P, et al. C-Peptide induces vascular smooth muscle cell proliferation: involvement of SRC-kinase, phosphatidylinositol 3-kinase, and extracellular signal-regulated kinase 1/2. Circ Res. 2006;99:1181-7. (Pubitemid 44808654)
36. Mughal RS, Scragg JL, Lister P, et al. Cellular mechanisms by which proinsulin C-peptide prevents insulin-induced neointima formation in human saphenous vein. Diabetologia. 2010;53:1761-71.
37. Al-Rasheed NM, Meakin F, Royal EL, et al. Potent activation of multiple signalling pathways by C-peptide in opossum kidney proximal tubular cells. Diabetologia. 2004;47:987-97. (Pubitemid 38918157)
38. Huang A, Yang YM, Yan C, et al. Altered MAPK signaling in progressive deterioration of endothelial function in diabetic mice. Diabetes. 2012;61:3181-8.
39. Hu Y, Dietrich H, Metzler B, et al. Hyperexpression and activation of extracellular signal-regulated kinases (ERK1/2) in atherosclerotic lesions of cholesterol-fed rabbits. Arterioscler Thromb Vasc Biol. 2000;20:18-26. (Pubitemid 30048342)
40. Fernandez-Hernando C, Ackah E, Yu J, et al. Loss of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease. Cell Metab. 2007;6:446-57. (Pubitemid 350163050)
41. Bhatt MP, Lim YC, Hwang J, et al. C-Peptide prevents hyperglycemia- induced endothelial apoptosis through inhibition of reactive oxygen species-mediated transglutaminase 2 activation. Diabetes. 2013;62:243-53.
42. •• Vasic D, Marx N, Sukhova G, et al. C-peptide promotes lesion development in a mouse model of arteriosclerosis. J Cell Mol Med. 2012;16:927-35. This study reveals that increased C-peptide levels lead to an augmentation of plaque development in hypercholesterolemic mice despite similar glucose and lipid levels.
43. Panero F, Novelli G, Zucco C, et al. Fasting plasma C-peptide and micro- and macrovascular complications in a large clinic-based cohort of type 1 diabetic patients. Diabetes Care. 2009;32:301-5.
44. Kim BY, Jung CH, Mok JO, et al. Association between serum C-peptide levels and chronic microvascular complications in Korean type 2 diabetic patients. Acta Diabetol. 2012;49:9-15.
45. Johansson BL, Wahren J, Pernow J. C-peptide increases forearm blood flow in patients with type 1 diabetes via a nitric oxide-dependent mechanism. Am J Physiol Endocrinol Metab. 2003;285:E864-70.
46. Ekberg K, Brismar T, Johansson BL, et al. C-peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy. Diabetes Care. 2007;30:71-6. (Pubitemid 46061294)
47. Johansson BL, Borg K, Fernqvist-Forbes E, et al. Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with type 1 diabetes mellitus. Diabet Med. 2000;17:181-9. (Pubitemid 30212289)
48. Patel N, Taveira TH, Choudhary G, et al. Fasting serum C-peptide levels predict cardiovascular and overall death in nondiabetic adults. J Am Heart Assoc. 2012;1:e003152.
49. Irwin ML, Duggan C, Wang CY, et al. Fasting C-peptide levels and death resulting from all causes and breast cancer: the health, eating, activity, and lifestyle study. J Clin Oncol. 2011;29:47-53.
50. Hsu CN, Chang CH, Lin YS, et al. Association of serum C-peptide concentrations with cancer mortality risk in pre-diabetes or undiagnosed diabetes. PLoS One. 2013;8:e55625.
51. Sari R, Balci MK. Relationship between C peptide and chronic complications in type-2 diabetes mellitus. J Natl Med Assoc. 2005;97:1113-8. (Pubitemid 41098538)
52. Yoon HJ, Cho YZ, Kim JY, et al. Correlations between glucagon stimulated C-peptide levels and microvascular complications in type 2 diabetes patients. Diabetes Metab J. 2012;36:379-87.
53. • Bo S, Gentile L, Castiglione A, et al. C-peptide and the risk for incident complications and mortality in type 2 diabetic patients: a retrospective cohort study after a 14-year follow-up. Eur J Endocrinol. 2012;167:173-80. In a retrospective analysis of more than 2,000 patients no correlation between cardiovascular mortality and C-peptide serum levels was found.
54. •• Marx N, Silbernagel G, Brandenburg V, et al. C-peptide levels are associated with mortality and cardiovascular mortality in patients undergoing angiography: the LURIC study. Diabetes Care. 2013;36(3):708-14. This study shows a positive association of C-peptide levels with cardiovascular mortality in a well-characterized study population.