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Objective. To elucidate the underlying mechanisms responsible for ββ-cell mass and function in response to intrauterine growth restriction (IUGR). Methods. Offspring from undernourished mother rats with birth weight <−−2 SD (IUGR group) and from standard-nourished rats with birth weight between mean ±±1SD normal birth weight (NBW group) were examined. Levels of fasting glucose, serum insulin, and insulin-like growth factor-1 (IGF-1) were analyzed. Entire pancreas or islet-like cell clusters (ICCs) were collected to evaluate relative ββ-cell mass and determine the genetic and protein profiles of pancreatic and duodenal homeobox 1 (Pdx1), Cacna1c and Cacna1d using real-time PCR, immunohistochemical staining, and western blotting at day (d) of birth and at d21 of age. Results. Fasting serum insulin and IGF-1 concentrations were significantly lower in the IUGR group than in the NBW group at d0 and d21. The levels of Pdx1 and insulin mRNAs in IUGR pancreas were also decreased. At birth, the ratios of ββ-cell mass to body weight were not significantly different between the two groups. However, by d21 the relative ββ-cell mass in IUGR had not grown to compensate for the increase in body weight, as compared to the NBW group ( p < 0.05). The Cacna1c and Cacna1d proteins were significantly higher in the NBW group than that in the IUGR group at birth, but there were no statistical differences at d21. Conclusion. Decreased Pdx1 levels and IGF-1 concentration restrain ββ-cell mass and insulin expression in rat offspring from undernourished mothers. However, Cacna1c and Cacna1d expression were able to reach normal levels as the IUGR rats were aged, indicating that these factors were not responsible for the IUGR rat phenotype of insulin resistance and ββ-cell dysfunction in later life. [ABSTRACT FROM AUTHOR]

This study investigated whether oxymatrine (OMT) treatment can ameliorate renal interstitial fibrosis in unilateral ureteral obstruction (UUO) mice model. Moreover, the potential mechanisms of such treatment were analyzed. Twenty-four C57/BL6 mice were randomly divided into three groups, namely sham group, vehicle plus unilateral ureteral obstruction (UUO)-treated group, and 100 mg/kg/d OMT plus UUO-treated group. All mice were euthanized seven days after surgery, and their kidneys were harvested. Renal injury, fibrosis, expression of proinflammatory cytokines, and the transforming growth factor-β1/Smads (TGF-β/Smads) and nuclear factor-kappa B (NF-κB)-signaling pathways were assessed. The results showed OMT significantly prevented kidney injury and fibrosis, as evidenced by decreased expression of collagen-1 and fibronectin. Furthermore, OMT administration inhibited the release of inflammatory factors including tumor necrosis factor-α, (TNF-α) interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as phosphorylated NF-κB p65. In addition, OMT blocked the activation of myofibroblasts by inhibiting the TGF-β/Smad3-signaling pathway. The findings indicate that OMT-attenuated renal fibrosis and inflammation, and this renoprotective effect may be ascribed to the inactivation of the TGF-β/Smad3 and NF-κB p65 pathways. [ABSTRACT FROM PUBLISHER]