C‐Peptide and Atherogenesis: C‐Peptide as a Mediator of Lesion Development in Patients with Type 2   Diabetes Mellitus?

Walcher, Daniel

doi:10.1155/2008/385108

Cited by 20 publications

(20 citation statements)

References 20 publications

(24 reference statements)

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“…Multivariable analyses to determine the effect of elevated C-peptide (T 3 ) compared to its normal values (terciles 1 plus 2) in the population with blood glucose < 126 mg/dL (n = 5673) consistently showed a significant effect of T 3 …”

Section: Resultsmentioning

confidence: 99%

C-peptide as a risk factor of coronary artery disease in the general population

León

García

Marcelino-Rodríguez

et al. 2015

Diabetes and Vascular Disease Research

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Objective: To analyse the association between serum C-peptide and coronary artery disease in the general population. Methods: Follow-up study of 6630 adults from the general population. They were stratified into group 1 (no insulin resistance: C-peptide < third tercile and glycaemia < 100 mg/dL), group 2 (initial insulin resistance: C-peptide ⩾ third tercile and glycaemia < 100 mg/dL) and group 3 (advanced insulin resistance: glycaemia ⩾ 100 mg/dL). Results: After 3.5 years of follow-up, group 2 had a higher incidence of myocardial infarction (relative risk (RR) = 4.2, 95% confidence interval (CI) = 1.7-10.6) and coronary artery disease (RR = 3.5, 95% CI = 1.9-6.6) than group 1. Group 3 also had increased incidences of both diseases. In multivariable analysis of the entire population, groups 2 and 3 showed significant risks of myocardial infarction and coronary artery disease (RR > 3 and RR > 2, respectively). However, when people with diabetes were excluded, the increased risks were corroborated only in group 2 for myocardial infarction (RR = 2.8, 95% CI = 1.1-6.9; p = 0.025) and coronary artery disease (RR = 2.4, 95% CI = 1.3-4.6; p = 0.007). Conclusion: Elevated C-peptide is associated with the incidence of myocardial infarction and coronary artery disease in the general population. It can be an earlier predictor of coronary events than impaired fasting glucose.

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Section: Resultsmentioning

confidence: 99%

C-peptide as a risk factor of coronary artery disease in the general population

León

García

Marcelino-Rodríguez

et al. 2015

Diabetes and Vascular Disease Research

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“…Epidemiological studies have found cross-sectional associations between low C-peptide levels and either microvascular or macrovascular complications and cardiovascular risk factors in type 2 diabetes (15,16,17), and most experiments with C-peptide supplementation have promoted vascular lesions and insulin resistance (24,25). In type 2 diabetes, elevations in C-peptide levels are usually observed as a consequence of insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have demonstrated the beneficial effects of C-peptide on vessels by inhibiting smooth muscle cell proliferation and migration and antiinflammatory activity in endothelial cells (2,27,28). Other studies have revealed C-peptide deposition in the arteriosclerotic lesions of diabetic patients, chemotactic activity towards monocytes and CD4C lymphocytes and the induction of vascular smooth muscle cell proliferation (24,25).…”

Section: Discussionmentioning

confidence: 99%

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

Gentile

Castiglione

et al. 2012

European Journal of Endocrinology

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Objective: C-peptide, a cleavage product of insulin, exerts biological effects in patients with type 1 diabetes mellitus, but its role in type 2 diabetes mellitus is controversial. Our aim was to examine the associations between fasting C-peptide levels and all-cause mortality, specific-cause mortality and the incidence of chronic complications in patients with type 2 diabetes. Design: Retrospective cohort study with a median follow-up of 14 years. Methods: A representative cohort of 2113 patients with type 2 diabetes mellitus and a subgroup of 931 individuals from this cohort without chronic complications at baseline from a diabetic clinic were studied. Results: Patients with higher C-peptide levels had higher baseline BMI and triglyceride and lower HDL-cholesterol values. During the follow-up, 46.1% of the patients died. In a Cox proportional hazard model, after multiple adjustments, no significant association was found between the C-peptide tertiles and all-cause mortality or mortality due to cancer, diabetes or cardiovascular diseases. In the subgroup of 931 patients without chronic complications at baseline, the incidence of microvascular complications decreased from the first to the third C-peptide level tertile, while the incidence of cardiovascular disease did not differ. The risks for incident retinopathy (hazard ratio (HR)Z0.33; 95% confidence interval (CI) 0.23-0.47), nephropathy (HRZ0.27; 95% CI 0.18-0.38) and neuropathy (HRZ0.39; 95% CI 0.25-0.61) were negatively associated with the highest C-peptide tertile, after adjusting for multiple confounders. Conclusions: Higher baseline C-peptide levels were associated with a reduced risk of incident microvascular complications but imparted no survival benefit to patients with type 2 diabetes mellitus.

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“…The internalisation of C-peptide was explored in human aortic endothelial cells (HAEC) and umbilical artery smooth muscle cells (UASMC), two important targets of C-peptide activity, especially in the context of vascular dysfunction leading to vascular complications in type 1 diabetes [13][14][15][16]. We found that in these cells C-peptide internalises from the cellular surface within punctate structures, most of them co-localizing with early endosomes.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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Aims/hypothesis There is increasing evidence that Cpeptide exerts intracellular effects in a variety of cells and could be beneficial in patients with type 1 diabetes. Exactly how C-peptide achieves these effects, however, is unknown. Recent reports showed that C-peptide internalised in the cytoplasm of HEK-293 and Swiss 3T3 cells, where it was not degraded for at least 1 h after uptake. In this study, we investigated the hypothesis that C-peptide is internalised via an endocytic pathway and traffics to classic endocytic organelles, such as endosomes and lysosomes. Methods We studied the internalisation of C-peptide in vascular endothelial and smooth muscle cells, two relevant targets of Cpeptide activity, by using Alexa Fluor-labelled C-peptide probes in living cells and immunohistochemistry employing confocal laser-scanning microscopy. To examine trafficking to subcellular compartments, we used fluorescent constructs tagged to RAB5A, member RAS oncogene family (RAB5A) to identify early endosomes, or to lysosomal-associated membrane protein 1 (LAMP1) to identify lysosomes.Results C-peptide internalised in the cytoplasm of cells within punctate structures identified as early endosomes. Internalisation was clearly detectable after 10 min of incubation and was blocked at 4°C as well as with excess of unlabelled C-peptide. A minor fraction of vesicles, which increased with culture time, co-localised with lysosomes. Uptake of C-peptide was reduced by monodansylcadaverine, a pharmacological compound that blocks clathrin-mediated endocytosis, and by nocodazole, which disrupts microtubule assembly. Conclusions/interpretation C-peptide internalises in the cytoplasm of cells by endocytosis, as demonstrated by its localisation in early endosomes. Endosomes might represent a signalling station, through which C-peptide might achieve its cellular effects.

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C‐Peptide and Atherogenesis: C‐Peptide as a Mediator of Lesion Development in Patients with Type 2 Diabetes Mellitus?

Cited by 20 publications

References 20 publications

C-peptide as a risk factor of coronary artery disease in the general population

C-peptide as a risk factor of coronary artery disease in the general population

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

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

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