Altered nuclear factor-kappaB inducing kinase expression in insulin-resistant mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Insulin resistance is an underlying feature of both type 2 diabetes and metabolic syndrome. Currently, it is unclear whether nuclear factor (NF)-κB inducing kinase (NIK) plays a role in the development of insulin resistance. The present in vivo study investigated the roles of NIK and IκB kinase α (IKKα) in obesity-induced insulin resistance using animal models.</p><p><b>METHODS</b>NIK expression was evaluated by Western blotting in male Lep(ob) mice and C57BL/6J mice fed a high-fat diet (HFD) (45% fat). After metformin and sulfasalazine treatment, NIK expression was investigated during the improvement of insulin resistance.</p><p><b>RESULTS</b>NIK was increased by about 1-fold in the renal tissues of Lep(ob) mice and C57BL/6J mice fed a HFD for 12 weeks. After 1 and 3 weeks of high-fat feeding, we observed an almost 50% decrease in NIK and IKKα expression in the liver and renal tissues of C57BL/6J mice. NIK expression was significantly lower in the liver and renal tissues of HFD-fed mice that were treated with insulin sensitizers, metformin and sulfasalazine. However, IKKα expression was increased after metformin treatment in both tissues.</p><p><b>CONCLUSION</b>These results suggest a possible role of NIK in the liver and renal tissues of insulin-resistant mice.</p>

Down-regulation of peroxisome proliferator-activated receptor γ coactivator-1α expression in fatty acid-induced pancreatic beta-cell apoptosis involves nuclear factor-κB pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pancreatic beta-cell apoptosis induced by lipotoxicity, to a large extent, contributes to the progression of type 2 diabetes. To investigate the mechanism of free fatty acid induced apoptosis, we aimed to study the effects of palmitic acid (PA) on the apoptosis and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression in βTC3 cells as well as the possible role of nuclear factor-κB (NF-κB) in this process.</p><p><b>METHODS</b>Hoechst 33258 was used to detect βTC3 cell apoptosis, which was induced by PA stimulation for 12 hours. PGC-1α expression was analyzed by reverse transcription polymerase chain reaction, IκB kinase β (IKKβ), IκBα, NF-κB-inducing kinase (NIK) and Rel-B expressions were analyzed by Western blotting. MG132 was employed to block the endogenous IκBα degradation before PA administration, and then its effect on PA-inducing cell apoptosis and PGC-1α mRNA expression was analyzed.</p><p><b>RESULTS</b>Significant increased cell apoptosis was found at the concentration of 0.5 mmol/L and 1.0 mmol/L PA administration. PA (0.5 mmol/L) could extensively reduced the expression of PGC-1α mRNA. After exposing βTC3 cells to 0.5 mmol/L PA for different time periods (0, 4, 6, 8, 10 and 12 hours), IKKβ protein expression increased while IκBα, NIK and Rel-B protein expression declined in a time-dependent manner. Pretreatment with MG132 to inhibit the degradation of IκBα, partially prevented the down-regulation of PGC-1α mRNA expression after 12-hour PA treatment in accordance with the decrease of PA induced apoptosis.</p><p><b>CONCLUSIONS</b>NF-κB canonical pathway was activated in PA-mediated βTC3 cell apoptosis, whereas non-canonical pathway was inhibited. Reduced PGC-1α expression by PA in βTC3 cells could involve the activation of canonical NF-κB pathway, so as to deteriorate the PA induced apoptosis.</p>

Beta-cell dysfunction is the primary contributor to the early postpartum diabetes among Chinese women with history of gestational diabetes mellitus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Women with a history of gestational diabetes mellitus (GDM) are at higher risk of future development of diabetes. This study investigated the risk factors associated with early postpartum abnormal glucose regulation (AGR) among Chinese women with a history of GDM.</p><p><b>METHODS</b>A total of 186 women with a history of GDM were screened for early postpartum AGR at 6-8 weeks after delivery. Those with AGR were given lifestyle intervention therapy and reevaluated in 6-12 months. The demographic, anthropometric, prenatal and delivery data were recorded. The plasma high-sensitivity C-reactive protein (HsCRP) and lipid concentration were measured, and insulin secretion were analyzed. Insulinogenic index Deltains30'/DeltaBG30', the homeostasis model assessment index (HOMA)-B, and HOMA-IR were calculated. Multiple regression analysis was performed to identify the risk factors.</p><p><b>RESULTS</b>Of the GDM women 28.0% (52/186) had AGR at 6-8 weeks after delivery; 45.2% (17/40) of these AGR women reminded abnormal after 6-12 month lifestyle intervention. Compared to the women who reverted to normal, women with consistent AGR showed significantly lower fasting insulin concentration, lower Deltains30'/DeltaBG30' as well as lower HOMA-B. No significant differences in age, body mass index (BMI), waist circumference, blood pressure, lipid level, HsCRP and HOMA-IR were observed between the two groups. Pre-pregnancy BMI = 25 kg/m(2), fasting glucose level = 5.6 mmol/L and/or 75 g oral glucose tolerance test (OGTT) 2 hours glucose level = 11.1 mmol/L during pregnancy were predictors for the AGR at 6-8 weeks after delivery. Deltains30'/DeltaBG30 = 1.05 was a significant risk contributor to the consistent early postpartum AGR.</p><p><b>CONCLUSION</b>There is a high incidence of early postpartum AGR among Chinese woman with prior GDM. Beta-cell dysfunction, rather than insulin resistance or inflammation, is the predominant contributor to the early onset and consistent AGR after delivery.</p>