ABSTRACT
Objective:To investigate the effect of high glucose on the release of interleukin (IL)-1β and IL-18 in placental trophoblast by activating NLRP3 inflammasome.Methods:Gestational diabetes mellitus(GDM) placentas and control placentas were collected and the expression levels of NLRP3 and Caspase-1 were determined. Human placental trophoblast HTR-8/SVneo were cultured and divided into control group(5.5 mmol/L glucose), high glucose group(25 mmol/L glucose), DMSO+ high glucose group, and Ac-YVAD-cmk(NLRP3 inflammasome inhibitor)+ high glucose group. The expression levels of NLRP3 and Caspase-1 in cells as well as the contents of IL-1β and IL-18 in the medium were determined.Results:The expression levels of NLRP3 and Caspase-1 in GDM placenta were higher than those in control placenta( P<0.05) and positively correlated with homeostasis model assessment of insulin resistant index(HOMA-IR) and fasting insulin. The expression levels of NLRP3 and Caspase-1 in HTR-8/SVneo cells and the secretion levels of IL-1β and IL-18 in high glucose group were higher than those in control group( P<0.05). Ac-YVAD-cmk significantly suppressed high glucose-stimulated IL-1β and IL-18 secretion( P<0.05). Conclusion:High glucose promotes the release of IL-1β and IL-18 from placental trophoblast via activating NLRP3 inflammasome.
ABSTRACT
The clinical data of 96 patients with type 2 diabetes mellitus (T2DM) treated in Department of endocrinology of our hospital from January 2016 to December 2017 were retrospectively analyzed. All patients had been treated with metformin ≥1 000 mg combined with sulfonylureas for>12 weeks and their glycosylated hemoglobin (HbA1c) was>7.5%. On the basis of the original scheme, 57 patients received oral sitagliptin (100 mg q.d, sitagliptin group) and 39 patients received insulin glargine injection (insulin group) for 26 weeks. The blood lipid, liver and kidney function were examined before and after treatment. The abdominal visceral fat area (VFA) was measured by CT scan. Results showed that the fasting plasma glucose (FPG) , 2-hour postprandial blood glucose (2 hPG) and HbA1c were significantly lower than baseline levels in both groups(P<0.05). The decrease of VFA in sitagliptin and insulin groups was by 9.6 (1.4,19.6)cm2 and by 8.3(-2.2,26.8) cm2, respectively; there was significant difference in variation of VFA before and after treatment between the two groups (P<0.05). There was no significant difference in blood pressure, liver function (ALT, AST) and estimated glomerular filtration rate (eGFR) before and after treatment in the sitagliptin group (P>0.05). Additional sitagliptin administration can effectively and safely reduce HbA1c and decrease the abdominal visceral fat content in T2DM patients who failed to metformin and sulfonylureas combined therapy.
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Objective To study the effect of hydrogen sulfide on the production of soluble fms-like tyrosine kinase 1 (sFlt-1) through a distintegrin and metalloproteinase 17 (ADAM17) in adipocytes. Methods 3T3-L1 cells were cultured and induced to differentiate into adipocytes, then treated with different doses of sodium hydrogen sulfide (NaHS), L-cysteine or transfected with cystathionine-γ-lyase ( CSE) siRNA, ADAM17 siRNA or treated with ADAM17 inhibitor, monoclonal antibody. 24 hours after treatment, the expression of ADAM17, CSE, and the production of sFlt-1 were determined. Results After the treatment of 10, 25, 50 nmol/L NaHS or 0. 5, 1. 0, 2. 0 μmol/L L-cysteine, the expression of ADAM17 and the production of sFlt-1 in adipocytes were significantly decreased, the higher dose of L-cysteine and sFlt-1, the lower expression of ADAM17 and the production of sFlt-1; the effect of 2.0 μmol/L L-cysteine decreasing the expression of ADAM17 and the production of sFlt-1 were reversed by transfection of CSE siRNA; after the transfection of ADAM17 siRNA and treatment of ADAM17 inhibitor or monoclonal antibody, the production of sFlt-1 in adipocytes were significantly decreased. Conclusion Hydrogen sulfide can reduce the production of sFlt-1 in adipocytes by downregulating the expression of ADAM17.
ABSTRACT
Objective To investigate the effect of hydrogen sulfide′s donor NaHS on the secretion of interleukin (IL)-1β and IL-18 in adipocytes and its mechanism.Methods 3T3-L1 cells were induced to differentiate into adipocytes and incubated with various concentrations of NaHS or 10 μg/ml caspase-1 inhibitor Ac-YVAD-CMK for 24 hours.The expressions of NLRP3(NLR family, pyrin domain containing 3), ASC(apoptosis associated speck-like protein containing CARD domain), caspase-1, IL-1β, and IL-18 in adipocytes, as well as the content of IL-1 and IL-18 in culture medium were determined.Results 10, 25, and 50 nmol/L NaHS significantly decreased NLRP3, ASC, and cleaved-caspase-1 protein expressions in adipocytes, as well as IL-1β and IL-18 contents in culture medium in a dose-dependent manner.The mature-IL-1β/pro-IL-1β, mature-IL-18/pro-IL-18 ratios in adipocytes and IL-1β and IL-18 contents in culture medium were also reduced by 10μg/ml Ac-YVAD-CMK.Conclusion Donor of hydrogen sulfide NaHS inhibits the maturation and secretion of IL-1β and IL-18 in adipocytes through downregulating the expression of NLRP3 inflammasome.