To investigate the effects of pioglitazone (PIO) on insulin resistance and first phase insulin secretion among obese and lean Chinese people with type 2 diabetes mellitus (T2DM). Sixty-eight drug-naïve patients with T2DM were treated with PIO for 16 weeks. Before and after the treatment, insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp test. Plasma insulin levels at 0, 3, 5, 7, and 10 min during intravenous glucose tolerance test were determined to calculate the first phase insulin secretion and pancreatic β-cell function. Circulating adiponectin levels were quantified. In both the lean and the obese patients with T2DM, the reduction of HbA1c following the PIO treatment was more than 1% (P < 0.001) and glucose infusion rate, acute insulin response, glucose disposal index, and β-cell glucose sensitivity increased significantly (P < 0.001). A multiple linear regression analysis showed that the improvements of first phase insulin secretion and insulin sensitivity were independently associated with the changes of HbA1c, but the change of first phase insulin secretion exhibited a higher correlation coefficient (R2 = 0.20, P = 0.001) than the change of insulin sensitivity did (R2 = 0.07, P = 0.040). The PIO treatment led to a significant increase in adiponectin levels only in the obese group (P < 0.05). A 16-week treatment of PIO significantly increased insulin sensitivity and β-cell function in the lean group as well as in the obese group among Chinese T2DM patients, demonstrating that both lean and obese diabetic adults would profit from PIO. The ChiCTR registry number is ChiCTR-OPC-17011571. Takeda Pharmaceutical Co. Ltd. and Pfizer Pharmaceutical Co. Ltd.
The intermittent fasting (IF) diet has profound benefits for diabetes prevention. However, the precise mechanisms underlying IF's beneficial effects remain poorly defined. Here, we show that the expression levels of cyclooxygenase-2 (COX-2), an enzyme that produces prostaglandins, are suppressed in white adipose tissue (WAT) of obese humans. In addition, the expression of COX-2 in WAT is markedly upregulated by IF in obese mice. Adipocyte-specific depletion of COX-2 led to reduced fractions of CD4+Foxp3+ Tregs and a substantial decrease in the frequency of CD206+ macrophages, an increase in the abundance of γδT cells in WAT under normal chow diet conditions, and attenuation of IF-induced antiinflammatory and insulin-sensitizing effects, despite a similar antiobesity effect in obese mice. Mechanistically, adipocyte-derived prostaglandin E2 (PGE2) promoted Treg proliferation through the CaMKII pathway in vitro and rescued Treg populations in adipose tissue in COX-2-deficient mice. Ultimately, inactivation of Tregs by neutralizing anti-CD25 diminished IF-elicited antiinflammatory and insulin-sensitizing effects, and PGE2 restored the beneficial effects of IF in COX-2-KO mice. Collectively, our study reveals that adipocyte COX-2 is a key regulator of Treg proliferation and that adipocyte-derived PGE2 is essential for IF-elicited type 2 immune response and metabolic benefits.
Objective To detect the level of total bile acid(TBA)in serum of women during normal pregnancy and the patients with intrahepatic cholestasis of pregnancy(ICP),and to compare with other liver function indexes in order to explore the evaluation of TBA detection in ICP.Methods The contrast detection of TBA,alanine aminotransferase(ALT),aspartate aminotransferase(AST)and alkaline phosphatase(ALP)were carried out in 20 patients with ICP and 30 normal pregnant women through Olympus AU2700 automatic biochemical analysis instrument by methods of cyclophorase.Results The level of TBA in the patients with ICP was significantly higher than that of the normal pregnant women[(35.1±7.0)μmol/L vs(2.9±1.6)μmol/L],and the difference had statistical significance(t=20.544,P0.01).In the patients with ICP,the abnorality rate of TBA(90.0%)was higher than that of ALT,AST and ALP(55%,50%,60%).Compared with normal pregnant women,the mean level of TBA in the patients with ICP increased 12.1 times,and that was significantly higher than the increasing multiples of ALT,AST and ALP(4.3,3.4,3.6).Conclusion The serum TBA is a sensitive index for diagnosis of intrahepatic cholestasis,and its sensibility and specificity have an advantage over other liver function indexes.
Aim To investigate the effect of Qin Ling Granule(QL) on chronic hepatic injury in rats.Methods The rat hepatic injury model was induced by the subcutaneous injection of 40% CCl_4(every three day for 42 days).The QL was given in three groups:2,5 and 10g·kg~(-1),ig.After 42 treatment days,the blood and liver of rats were taken.The liver function,alanine transaminase(ALT)、alkaline phosphatase(ALP)、aspartate aminotransferase (AST)、total protein(TP) and albumin(ALb) were determined.Histopathological changes were examined by optical microscopy.Results In model group:(1)The levels of TLP and Alb reduced.(2)The level of AP、ALT and AST increased significantly.(3)Pathologic histology:Degeneration,necrosis and hepatic fibrosis in liver tissues were seen under optical microscopy.In QL treated groups:all the changes above were improved significantly in middle and high dose treated groups.Conclusion QL possessed the protective effect on chronic hepatic injury and fibrosis induced by CCl_4.
Objective: To study the mechanism of proliferation inhibited by five natural medicines in lens epithelial cell via blockers of signal transduction.Methods: The proliferations of cultured LEC were induced by rhbFGF,which were incubated with five natural medicines,Curcumin(Cur),elemene(Ele),arsenite trioxide(As2O3),triptolide(Tri) and rhizoma curcumae(Rc) respectively.Meanwhile the LEC were incubated with four blockers of signal transduction,H7、W7、PD98059和nicardipine respectively.The proliferating cell nuclear antigen(PCNA)of LEC were detected via flow cytometer(FCM).Results:The PCNA expression of LEC in proliferation group were higher than that in control group(P0.01),there were decreased in groups Cur,Ele,As2O3,Tri and Rc significantly(P0.01).The signal pathways of proliferation inhibited by Cur can be blocked by H7,PD98059和nicardipine.It can be blocked by H7and W7in group Ele and groups As2O3,can be blocked by W7and nicardipine in group Tri,can be blocked by H7,W7,PD98059 and nicardipine in group Rc.Conclusion: The mechanism of LEC proliferation inhibited by five natural medicines,Cur,Ele,As2O3,Tri and Rc,may be the signal pathways of protein kinase C(PKC),mitogen activated protein kinase(MAPK),Ca2+-calmodulin(CaM) and calcium channel,which provided the scientific basis for pursuit of effective medicine to prevent and treat after cataract.
The incidence of acute liver and kidney injury in pregnancy is companied by Preeclampsia (PE), which has remained a major cause of maternal and fetal morbidity, and mortality. Therefore, a significant treatment to protect against liver and kidney injury of PE requires new drugs to develop potential therapeutic benefits to the clinic. Baicalin played protection role on inhibition of cell apoptosis which is a potential drug for keep liver and kidney from acute injury on PE patients. In this study, we made PE rat disease model with liver and kidney acute injury, and then used low-, medium-, and high-dose of Baicalin to treat PE rat, respectively. We found that Baicalin attenuated acute injury symptoms and inhibited apoptosis of rat liver and kidney tissues. The intervention of Baicalin increased the expression of anti-apoptotic protein XIAP and Bcl-2, reduced the expression of apoptotic protein Caspase-9 in rat liver; and similarly, Baicalin increased the expression of Bcl-2, while inhibited Caspase-9 and AT1 in rat kidney. Interestingly, Baicalin intervention with medium dose showed a better function for inhibiting apoptosis. Our data suggests that Baicalin is a potentially therapeutic candidate for preventing liver and kidney damage, which shed a light on therapeutic benefit for PE rat models.
Group 2 innate lymphoid cells (ILC2s) in white adipose tissue (WAT) promote WAT browning and assist in preventing the development of obesity. However, how ILC2 in adipose tissue is regulated remains largely unknown. Here, our study shows that ILC2s are present in brown adipose tissue (BAT) as well as subcutaneous and epididymal WAT (sWAT and eWAT). The fractions of ILC2s, natural killer T (NKT) cells and eosinophils in sWAT, eWAT and BAT are significantly decreased by high-fat-diet (HFD) feeding and leptin deficiency-induced obesity. Consistent with this, the adipose expression and circulating levels of IL-33, a key inducing cytokine of ILC2, are significantly downregulated by obesity. Furthermore, administration of IL-33 markedly increases the fraction of ILC2 and eosinophil as well as the expression of UCP1 and tyrosine hydroxylase (TH), a rate-limiting enzyme in catecholamine biosynthesis, in adipose tissue of HFD-fed mice. On the other hand, cold exposure induces the expression levels of IL-33 and UCP1 and the population of ILC2 and eosinophil in sWAT, and these promoting effects of cold stress are reversed by neutralization of IL-33 signaling in vivo Moreover, the basal and cold-induced IL-33 and ILC2/eosinophil pathways are significantly suppressed by sympathetic denervation via local injection of 6-hydroxydopamine (6-OHDA) in sWAT. Taken together, our data suggest that the ILC2/eosinophil axis in adipose tissue is regulated by sympathetic nervous system and obesity in IL-33-dependent manner, and IL-33-driven ILC2/eosinophil axis is implicated in the development of obesity.
ILC2s are present in adipose tissue and play a critical role in regulating adipose thermogenesis. However, the mechanisms underlying the activation of adipose-resident ILC2s remain poorly defined. Here, we show that IL-33, a potent ILC2 activator, stimulates phosphorylation of AMPK at Thr172 via TAK1 in primary ILC2s, which provides a feedback mechanism to inhibit IL-33-induced NF-κB activation and IL-13 production. Treating ILC2s with adiponectin or an adiponectin receptor agonist (AdipoRon) activated AMPK and decreased IL-33-NF-κB signaling. AdipoRon also suppressed cold-induced thermogenic gene expression and energy expenditure in vivo. In contrast, adiponectin deficiency increased the ILC2 fraction and activation, leading to up-regulated thermogenic gene expression in adipose tissue of cold-exposed mice. ILC2 deficiency or blocking ILC2 function by neutralization of the IL-33 receptor with anti-ST2 diminished the suppressive effect of adiponectin on cold-induced adipose thermogenesis and energy expenditure. Taken together, our study reveals that adiponectin is a negative regulator of ILC2 function in adipose tissue via AMPK-mediated negative regulation of IL-33 signaling.
To analyze the correlation of serum progesterone (PROG) level with blood biochemical parameters and common traditional Chinese medicine (TCM) syndromes in male patients with type 2 diabetes mellitus (T2DM).We collected the clinical data of 192 male patients with T2DM, who were admitted in the Department of Endocrinology, Nanjing Hospital of Chinese Medical Affiliated to Nanjing University of Chinese Medicine between January, 2018 and March, 2019. The general clinical data, C-peptide level, blood glucose level, glycated hemoglobin (HbA1c), HOMA, blood lipid level, and sex hormones were compared between the patients with normal PROG and elevated PROG levels and also between the patients with two common TCM syndromes, namely qi and Yin deficiency syndrome and damp- heat accumulation in the spleen syndrome. We further compared the sex hormones, C-peptide level, HOMA, HbA1c, and blood glucose level among the patients with the two TCM syndromes having normal or elevated PROG levels.Compared with those in patients with normal PROG level, BMI, C-peptide, HOMA-β, and HOMA2-IR were significantly lowered and HOMA-IS, E2, and T were significantly increased in patients with elevated PROG level; no statistical differences were found in age, disease duration, waist-to-hip ratio (WHR), smoking history, blood pressure, blood glucose, blood lipids, HbA1c, LH, FSH or PRL between the two groups. Compared with the patients with damp-heat accumulation syndrome group, the patients with qi and Yin deficiency syndrome were older and had a longer disease duration, a greater BMI, and higher levels of PROG, C-Peptide, HOMA-β, HOMA2-IR and HOMA-IS, but the smoking history, WHR, HbA1c, blood glucose, and sex hormone levels were comparable between the two groups. Among the 4 groups of patients with different PROG levels and TCM syndromes, significant differences were found in the levels of C-peptide, HOMA-β, HOMA-IS, HOMA2-IR, PROG, E2, T, LH and FSH, and the patients with qi and Yin deficiency syndrome as well as an elevated PROG level had the lowest C-peptide level, HOMA-β and HOMA2-IR and the highest HOMA-IS, PROG, E2, T, LH and FSH.An elevated PROG level is closely related to islet cell dysfunction and TCM syndrome types in male patients with T2DM.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)