We evaluated how low-level (3 ppm) subchronic inorganic arsenic (iAs) exposure from prenatal developmental stages until adult life affects glucose homeostasis. Biochemical parameters of glucose and lipid metabolism, pancreatic insulin and glycosylated haemoglobin were determined in 4-month-old female offspring of adult Wistar rats. Pancreatic histology was also performed. Statistical comparisons between control and iAs-treated groups were performed by unpaired two-tailed Student's t-test. Statistical significance was set at p<0.05. We found that iAs treatment resulted in an impaired glucose tolerance test, suggestive of impaired glucose metabolism. This group was found to have hyperglycaemia and high levels of HOMA-IR, glycosylated haemoglobin, cholesterol and pancreatic insulin compared to control rats. However, plasma insulin, triglycerides and high-density lipoprotein cholesterol were not different from control rats. Moreover, β-cell damage found in iAs-treated rats consisted of cells with a nucleus with dense chromatin and predominance of eosinophilic cytoplasm, as well as changes in the pancreatic vasculature. The current study provided evidence that subchronic iAs exposure at 3 ppm from prenatal developmental stages to adult life resulted in damage to pancreatic β cells, affected insulin secretion and demonstrated altered glucose homeostasis, thus supporting a causal association between iAs exposure and diabetes.

To ascertain determinants of the change of RIHP during saline volume expansion, plasma protein concentration ([Pr]p),hematocrit (Ht) and time courses of left renal medullary blood flow (RMBF),left renal cortical blood flow (RCBF), left RIHP and left renal excretory response were evaluated simultaneously in anesthetized,acutely left renal denervated, hormonally clampped and renal perfusion pressure (RPP) controlled rats before (C) and during volume expansion (E) with either saline (SVE: 1.1 ml/min i.v., 5% body wt) or 5% BSA saline solution (AVE: 0.30 ml/min, i.v., 1.4% body wt).At post‐expansion, RPP vs %RMBF, RPP vs %RCBF and RPP vs RIHP relationships were obtained. Blood flows were measured by laser‐Doppler flowmetry and RIHP by sub‐capsular catheter. There were no statistical significant differences between groups in delta(Δ = E‐C) of urinary flow (V), Uosm, UosmV, UNaV and Ht. Δ[Pr]p was −0.89 ± 0.09 g/dl in SVE group vs −0.02 ± 0.08 g/dl in AVE group (p = 0.0001). ΔRIHP was 2.9 ± 0.8 mmHg in SVE group,vs 0.5 ± 0.3 mmHg in AVE group(p = 0.006).ΔRIHP showed interaction group × time and %RMBF showed effect of group and time, AVE group showing greater increase in %RMBF than SVE group. A linear relationship between RPP vs ΔRIHP was observed in both groups. Conclusion: Data modeling indicated that Δ[Pr]p and ΔHt are primary determinants of ΔRIHP in SVE. Supported by: SMRF05‐UASLP