Brief reportGenome-wide search for susceptibility genes to type 2 diabetes in West Africans: Potential role of C-peptide
Introduction
C-peptide is secreted into the bloodstream by the pancreas along with insulin. Since half-life of C-peptide in plasma is longer than insulin, C-peptide concentration is 5–10 times higher than that of insulin. The main physiological role of C-peptide is to facilitate the folding of the pro-insulin molecule. However, recent studies have been demonstrated physiological effects of C-peptide involving renal and nerve function, and the stimulation of whole body glucose uptake in patients with type 1 diabetes [1], [2], [3], [4]. For example, a positive linear relationship has been observed between residual plasma C-peptide concentration and erythrocyte Na+–K+-ATPase activity in a cohort of patients with T2D [5]. Under diabetic conditions, Na+, K+-ATPase activity is decreased in different cell types and might be involved in the pathogenesis of various diabetic complications [6], [7], [8]. In contrast, similar physiologic effects of C-peptide have not been observed in health subjects or animals suggesting a saturation of the mechanisms of C-peptide action in health subjects [6]. These growing physiologic importances of C-peptide prompted us to considerate C-peptide as a phenotype in whole-genome linkage studies for T2D.
Section snippets
Subjects
Participants included in these analyses were enrolled in the AADM study as described in detail by Rotimi et al. [9], [10]. The protocol was approved by Institutional Review Board (IRB) of each institution and written informed consent was obtained from all participants. At the time of these analyses, the AADM study enrolled only affected pairs with T2D. In this regard, data on parents and other family members were not available. Participants were enrolled from three centers in Nigeria (Enugu,
Results
Clinical characteristics of the affected subjects are shown in Table 1. The study sample included 691 persons (59.3% women) with T2D. The mean age was 53 years, age at diagnosis was 48 years and mean duration of diabetes at the time of the study was 7 years. Mean value of C-peptide, insulin and glucose were 1.25 ng/ml, 21.70 μU/ml, and 201.00 mg/dl, respectively. The correlation between the log C-peptide value and covariates are shown in Table 2. The maximum likelihood heritability estimates for log
Discussion
Physiologically, C-peptide has been shown to increase forearm muscle blood flow [17], to enhance oxygen uptake and capillary diffusion capacity in the exercising forearm [2]. Under diabetic condition C-peptide has been shown to: (1) redistribute micro-vascular skin blood flow in C-peptide negative patients [18]; (2) improve micro-vascular complications, such as diabetic nephropathy and diabetic neuropathy [1], [3]; (3) attenuate Na+–K+-ATPase activity in different cell types [19], [20]; and (4)
Acknowledgements
Support for the AADM study is provided by NIH grant no. 3T37TW00041-03S2 from the National Center for Minority Health and Health Disparities. This project is also supported other NIH institutes (NGHRI, and NIDDK; DK-54001). Genotyping was done by the Center for Inherited Disease Research (CIDR). Some of the results of this paper were obtained using the program S.A.G.E. which is supported by a U.S. Public Health Service Resource Grant (RR03655) from the National Center for Research Resources.
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