Literature DB >> 16195866

Human proinsulin C-peptide prevents proliferation of rat aortic smooth muscle cells cultured in high-glucose conditions.

Y Kobayashi1, K Naruse, Y Hamada, E Nakashima, K Kato, N Akiyama, H Kamiya, A Watarai, M Nakae, Y Oiso, J Nakamura.   

Abstract

AIMS/HYPOTHESIS: Proinsulin C-peptide is involved in several biological activities. However, the role of C-peptide in vascular smooth muscle cells is unclear. We therefore investigated its effects, in vascular smooth muscle cells in high-glucose conditions.
METHODS: Rat aortic smooth muscle cells were cultured with 5.5 or 20 mmol/l glucose with or without C-peptide (1 to 100 nmol/l) for 3 weeks. Proliferation activities, the protein expression of platelet-derived growth factor (PDGF)-beta receptor, the phosphorylation of p42/p44 mitogen-activated protein (MAP) kinases, and glucose uptake were measured.
RESULTS: The proliferation activities increased approximately three-fold under high-glucose conditions (p<0.05). C-peptide suppressed hyperproliferation activities that were induced by high glucose. This happened in a dose-dependent manner from 1 to 100 nmol/l of C-peptide. C-peptide (10 and 100 nmol/l) inhibited the increased protein expression of PDGF-beta receptor and the phosphorylation of p42/p44 MAP kinases that had been induced by high glucose (p<0.05). Furthermore, 100 nmol/l of C-peptide augmented the impaired glucose uptake in the high-glucose conditions. CONCLUSIONS/
INTERPRETATION: These observations suggest that C-peptide could prevent diabetic macroangiopathy by inhibiting smooth muscle cell growth and ameliorating glucose utilisation in smooth muscle cells. C-peptide may thus be a novel agent for treating diabetic macroangiopathy in patients with type 1 and type 2 diabetes.

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Year:  2005        PMID: 16195866     DOI: 10.1007/s00125-005-1942-9

Source DB:  PubMed          Journal:  Diabetologia        ISSN: 0012-186X            Impact factor:   10.122


  31 in total

1.  Prevention of vascular and neural dysfunction in diabetic rats by C-peptide.

Authors:  Y Ido; A Vindigni; K Chang; L Stramm; R Chance; W F Heath; R D DiMarchi; E Di Cera; J R Williamson
Journal:  Science       Date:  1997-07-25       Impact factor: 47.728

2.  Enhancement and inhibition of mitogenic action of insulin-like growth factor I by high glucose in cultured bovine retinal pericytes.

Authors:  K Naruse; F Sakakibara; J Nakamura; N Koh; N Hotta
Journal:  Life Sci       Date:  1996       Impact factor: 5.037

3.  Rat C peptide I and II stimulate glucose utilization in STZ-induced diabetic rats.

Authors:  L Li; Y Oshida; M Kusunoki; K Yamanouchi; B L Johansson; J Wahren; Y Sato
Journal:  Diabetologia       Date:  1999-08       Impact factor: 10.122

4.  C-peptide improves autonomic nerve function in IDDM patients.

Authors:  B L Johansson; K Borg; E Fernqvist-Forbes; T Odergren; S Remahl; J Wahren
Journal:  Diabetologia       Date:  1996-06       Impact factor: 10.122

5.  C-peptide induces a concentration-dependent dilation of skeletal muscle arterioles only in presence of insulin.

Authors:  M E Jensen; E J Messina
Journal:  Am J Physiol       Date:  1999-04

6.  Effects of C-peptide on renal function at the early stage of experimental diabetes.

Authors:  M Sjöquist; W Huang; B L Johansson
Journal:  Kidney Int       Date:  1998-09       Impact factor: 10.612

7.  Effects of C-peptide on glomerular and renal size and renal function in diabetic rats.

Authors:  B Samnegård; S H Jacobson; G Jaremko; B L Johansson; M Sjöquist
Journal:  Kidney Int       Date:  2001-10       Impact factor: 10.612

8.  C-peptide prevents and improves chronic Type I diabetic polyneuropathy in the BB/Wor rat.

Authors:  A A Sima; W Zhang; K Sugimoto; D Henry; Z Li; J Wahren; G Grunberger
Journal:  Diabetologia       Date:  2001-07       Impact factor: 10.122

9.  C-peptide increases forearm blood flow in patients with type 1 diabetes via a nitric oxide-dependent mechanism.

Authors:  Bo-Lennart Johansson; John Wahren; John Pernow
Journal:  Am J Physiol Endocrinol Metab       Date:  2003-06-10       Impact factor: 4.310

10.  Human C-peptide dose dependently prevents early neuropathy in the BB/Wor-rat.

Authors:  W Zhang; M Yorek; C R Pierson; Y Murakawa; A Breidenbach; A A Sima
Journal:  Int J Exp Diabetes Res       Date:  2001
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  16 in total

1.  C-peptide is internalised in human endothelial and vascular smooth muscle cells via early endosomes.

Authors:  P Luppi; X Geng; V Cifarelli; P Drain; M Trucco
Journal:  Diabetologia       Date:  2009-08-07       Impact factor: 10.122

Review 2.  C-Peptide and its career from innocent bystander to active player in diabetic atherogenesis.

Authors:  Corinna Lebherz; Nikolaus Marx
Journal:  Curr Atheroscler Rep       Date:  2013-07       Impact factor: 5.113

3.  Cellular mechanisms by which proinsulin C-peptide prevents insulin-induced neointima formation in human saphenous vein.

Authors:  R S Mughal; J L Scragg; P Lister; P Warburton; K Riches; D J O'Regan; S G Ball; N A Turner; K E Porter
Journal:  Diabetologia       Date:  2010-05-12       Impact factor: 10.122

4.  Human C-peptide antagonises high glucose-induced endothelial dysfunction through the nuclear factor-kappaB pathway.

Authors:  P Luppi; V Cifarelli; H Tse; J Piganelli; M Trucco
Journal:  Diabetologia       Date:  2008-05-21       Impact factor: 10.122

Review 5.  Advanced glycation end products and C-peptide-modulators in diabetic vasculopathy and atherogenesis.

Authors:  Daniel Walcher; Nikolaus Marx
Journal:  Semin Immunopathol       Date:  2009-04-05       Impact factor: 9.623

Review 6.  Physiological effects and therapeutic potential of proinsulin C-peptide.

Authors:  Gina L C Yosten; Christine Maric-Bilkan; Patrizia Luppi; John Wahren
Journal:  Am J Physiol Endocrinol Metab       Date:  2014-09-23       Impact factor: 4.310

7.  C-Peptide in the vessel wall.

Authors:  Daniel Walcher; Nikolaus Marx
Journal:  Rev Diabet Stud       Date:  2009-11-10

8.  Anti-inflammatory properties of C-Peptide.

Authors:  Jaime Haidet; Vincenza Cifarelli; Massimo Trucco; Patrizia Luppi
Journal:  Rev Diabet Stud       Date:  2009-11-10

Review 9.  Proinsulin C-peptide: friend or foe in the development of diabetes-associated complications?

Authors:  Lina Nordquist; M Johansson
Journal:  Vasc Health Risk Manag       Date:  2008

10.  Renal and vascular benefits of C-peptide: Molecular mechanisms of C-peptide action.

Authors:  Lina Nordquist; Fredrik Palm; Bradley T Andresen
Journal:  Biologics       Date:  2008-09
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