Serum levels of interleukin 6, C-reactive protein, vascular cell adhesion molecule 1, and monocyte chemotactic protein 1 in relation to insulin resistance and glucose intolerance--the Chennai Urban Rural Epidemiology Study (CURES).

The aim of this cross-sectional study was to assess the association of insulin resistance (IR) with inflammatory molecules C-reactive protein (CRP), interleukin 6 (IL-6), vascular cell adhesion molecule 1 (VCAM-1), and monocyte chemotactic protein 1 (MCP-1) in urban South Indian subjects. The following groups were selected from the population-based Chennai Urban Rural Epidemiology Study: group 1 composed of 50 healthy subjects with normal glucose tolerance without IR; group 2 consisted of 50 normal glucose-tolerant subjects with IR as defined by homeostasis model assessment of IR (HOMA-IR); group 3 consisted of 50 subjects with impaired glucose tolerance (IGT); and groups 4 and 5 each comprised 50 newly diagnosed and known type 2 diabetic subjects, respectively. The inclusion criteria included nonsmokers; normal resting 12-lead electrocardiogram; and absence of angina, myocardial infarction, or history of any known vascular, infectious, or inflammatory diseases, and not on statins or aspirin. Normal glucose tolerance without IR had the lowest values of CRP, IL-6, and VCAM-1 (CRP, 1.32 mg/L; IL-6, 12.56 pg/mL; VCAM-1, 277 pg/mL) followed by normal glucose tolerance with IR (CRP, 2.25 mg/L; IL-6, 20.97 pg/mL; VCAM-1, 289 pg/mL), impaired glucose tolerance (CRP, 2.37 mg/L; IL-6, 22.11 pg/mL; VCAM-1, 335 pg/mL), newly diagnosed diabetic subjects (CRP, 3.24 mg/L; IL-6, 23.21 pg/mL; VCAM-1, 568 pg/mL), and the highest levels were in the known diabetic subjects (CRP, 4.08 mg/L; IL-6, 29.44 pg/mL; VCAM-1, 577 pg/mL). This trend was statistically significant (P < .001). However, monocyte chemotactic protein 1 did not show such a trend and did not differ significantly between groups. In nondiabetic subjects, Pearson correlation analysis revealed that CRP (r = 0.299; P < .001) and IL-6 (r = 0.180, P = .025) had a significant correlation with HOMA-IR. Monocyte chemotactic protein 1 did not show any correlation with HOMA-IR. Multiple linear regression analysis revealed CRP to be significantly associated with HOMA-IR (beta = .229; P < .001) and this was unaltered by the addition of waist and IL-6 into the model (beta = .158; P = .028). In conclusion, this study shows that in Asian Indians, inflammatory markers (CRP, IL-6, and VCAM-1) increase with increasing degrees of glucose intolerance.

Three-dimensional solution structures of the chromodomains of cpSRP43.

Chloroplasts contain a unique signal recognition particle (cpSRP). Unlike the cytoplasmic forms, the cpSRP lacks RNA but contains a conserved 54-kDa GTPase and a novel 43-kDa subunit (cpSRP43). Recently, three functionally distinct chromodomains (CDs) have been identified in cpSRP43. In the present study, we report the three-dimensional solution structures of the three CDs (CD1, CD2, and CD3) using a variety of triple resonance NMR experiments. The structure of CD1 consists of a triple-stranded beta-sheet segment. The C-terminal helical segment typically found in the nuclear chromodomains is absent in CD1. The secondary structural elements in CD2 and CD3 include a triple-stranded antiparallel beta-sheet and a C-terminal helix. Interestingly, the orientation of the C-terminal helix is significantly different in the structures of CD2 and CD3. Critical comparison of the structures of the chromodomains of cpSRP43 with those found in nuclear chromodomain proteins revealed that the diverse protein-protein interactions mediated by the CDs appear to stem from the differences that exist in the surface charge potentials of each CD. Results of isothermal titration calorimetry experiments confirmed that only CD2 is involved in binding to cpSRP54. The negatively charged C-terminal helix in CD2 possibly plays a crucial role in the cpSRP54-cpSRP43 interaction.