Human proinsulin C-peptide prevents proliferation of rat aortic smooth muscle cells cultured in high-glucose conditions.
OBJECTIVE
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
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.
Kobayashi
Y
Y
Division of Metabolic Diseases, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Naruse
K
K
Hamada
Y
Y
Nakashima
E
E
Kato
K
K
Akiyama
N
N
Kamiya
H
H
Watarai
A
A
Nakae
M
M
Oiso
Y
Y
Nakamura
J
J
D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D002096:C-Peptide / Q000494:pharmacology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects; D010766:Phosphorylation; D011384:Proinsulin / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000187:drug effects / Q000378:metabolism
D002096:C-Peptide; D003470:Culture Media; D011384:Proinsulin; D020797:Receptor, Platelet-Derived Growth Factor beta; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose