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The prevalence of energy metabolism-related metabolic diseases, such as diabetes, fatty liver, and cardiovascular diseases, is trending upwards over years. Not only glucose and lipid metabolism but also amino acid metabolism are involved in the pathogenesis, among which branched-chain amino acids are most widely studied. Isoleucine is an important branched-chain amino acid. Its relevance to metabolic diseases has caught more attention in recent years. This review is to highlight advances in isoleucine and energy metabolism.
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Organoids are complex tiny organ-like model systems formed by three-dimensional culture in vitro, based on the self-renew and self-organization of stem cells. This article reviewed the recent progress in organoids construction from tissues involved in the regulation of glucose homeostasis and chronic diabetic microvascular complications, and their applications in diabetes mellitus. Organoid technology is expected to further promote the progress of diabetes research in disease modeling, personalized medicine, and regenerative medicine.
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Objective:To evaluate the value of plasma aldosterone concentration (PAC)/renin concentration (PRC) ratio (ARR) combined with aldosterone, renin, and sodium/potassium ratio in the diagnosis of primary aldosteronism (PA).Methods:From January 2017 to October 2019, 105 patients were admitted to our hospital and diagnosed as PA and essential hypertension (EH) by clinical manifestations, laboratory examination and surgical pathological biopsy.The optimum cut-off point of ARR, PRC, PAC, plasma sodium-potassium ratio were determined by the Receiver Operating Characteristic (ROC). The sensitivity, specificity and Youden index at the optimum cut-off point were calculated in a separate test. By means of diagnostic test, the best cut-off points of ARR were tested in series with the best cut-off points of PRC, PAC and serum sodium/potassium ratio, respectively, and their specificity were calculated.Results:The area under the AUC of supine ARR was greater than that of vertical ARR (0.966 vs 0.946, Z= 1.380, P= 0.168), but there was no statistical difference. The optimum cut-off point of supine ARR was 28.64(pg/ml)/(pg/ml), with a sensitivity of 92.4% and specificity of 90.5%. The sensitivity of the combined PRC test was 79.0% and the specificity was 94.3%. The sensitivity of the combined PAC test was 65.7% and the specificity was 95.2%. The sensitivity of the combined serum sodium/potassium ratio was 50.5% and the specificity was 96.2%. The optimal cut-off of vertical ARR was 22.10 (pg/ml)/(pg/ml), with 91.4% specificity and 85.7% specificity. The sensitivity of vertical ARR combined with PRC was 78.1%, specificity was 89.5%. The sensitivity of combined PAC was 74.3%, specificity was 92.4%, and the sensitivity of combined sodium/potassium ratio was 50.5%, specificity was 95.2%. Conclusions:There was little difference in the diagnostic performance of PA between vertical and supine ARR values. The specificity of PA screening by ARR alone was high, and the specificity and accuracy of PA diagnosis could be improved by combining PRC, PAC and sodium/potassium ratio.
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Objective To investigate the prevalence of dyslipidemia and the relationship between breakfast frequency and dyslipidemia in residents over 40 years old in Yiling area of Yichang City in Hubei Province. Methods A random sampling was conducted, and 10 420 inhabitants were investigated during 2011 to 2012. Results The morbidity of dyslipidemia was 64. 0%. It was significantly higher in female than in male (65. 9% vs 60. 6%). Compared with regular breakfast eaters, non-breakfast eaters had significantly higher morbidity of higher blood low density lipoprotein-cholesterol(LDL-C) and hypertriglyceridemia(P<0. 05). The risk of elevated serum LDL-C was higher in the non-breakfast eaters group(OR=2. 382, 95%CI 1. 300-4. 367, P=0. 019) after adjusted by age, sex, smoking, drinking, etc. Conclusions Compared with regular breakfast eaters, breakfast skippers had significantly higher morbidity of dyslipidemia. Eating breakfast on daily basis may have a significant protective effect on preventing dyslipidemia.
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Objective To investigate whether liraglutide treatment can prevent catch-up fat in high-fat dietinduced catch-up growth rats,and to discuss the possible underlying mechanisms.Methods Sixty-four SpragueDawley rats were stratified into 4 groups:normal control group,catch-up growth (CUG) group,catch-up growth with liraglutide treatment (CUGL) group,and catch-up growth with liraglutide plus exendin (9-39) treatment (CUGLE) group.All the catch-up growth animals underwent a4 week high-fat diet re-feeding phase after a4 week food restriction phase.Body weight and food intake were measured every day.At the end of food restriction and re-feeding,body composition was measured via Dual energy X-ray absorptiometry.After the rats were sacrificed,body fat distribution and plasma lipid levels were determined.Results By the end of catch-up growth,body weight,energy intake,Lee' s index,fat body mass,visceral adipose tissue/body weight,subcutaneous adipose tissue/body weight,triglyceride,free fatty acid,low density lipoprotein-cholesterol levels were lower in CUGL rats compared with CUG rats (all P＜0.01).There were no significant differences in energy intake,body composition,fat body mass,and blood lipid levels between CUGLE rats and CUG rats,while the weight of CUGLE rats was significantly lower than CUG ones.Conclusions Liraglutide infusion protects rats with high-fat diet induced catch-up growth from catch-up fat mainly via a glucagon-like peptide-1 receptor dependent manner.
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Cultured primary human umbilical vein endothelial cells (HUVECs) were divided into 4 groups:normal control( NG ),persistent high glucose ( HG ),hyperglycemia group ( TG ),and mannitol control ( MA )groups.After 1,4,and 7 days of culture,cells were collected.Cell proliferation,cell apoptosis,ROS,SOD,MDA,and NO level,eNOS mRNA and protein level were measured.Endothelial cell proliferation was inhibited in HG,TG,and MA groups compared with NG group.Hyperglycemia memory induced apoptosis of endothelial cells,increased ROS and MDA generation,and down-regulated intracellular SOD level,findings similar to those in HG group.After 24 h of culturing,eNOS expression and NO generation in both HG and TG groups were higher than those in NG group.However,after 7 days of culturing,eNOS expression and NO generation in both HG and TG groups were lower than those in NG group.These results suggest that in hyperglycemia memory cell model,transient hyperglysemia may lead to persistent imbalance in oxidative stress and reduce endothelium-derived relaxing factor NO level,indicating that hyperglycemia memory may play an important role in persistent vascular endothelial cell injury.
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To explore the relationship between serum thyroid stimulating hormone (TSH) level and obesity and nonalcoholic fatty liver disease (NAFLD) in euthyroid subjects, 1322 subjects were subjected to a questionnaire survey and physical examination. Fasting blood samples were collected to test serum TSH, plasma glucose and lipids. Fatty liver was diagnosed by type B ultrasonography. The relationship between serum TSH level and body mass index (BMI), percentage of body fat and NAFLD was analyzed. The results showed that serum TSH level was significantly higher in females than in males at the same group, and it was significantly higher in overweight group than in control group. Levels of body weight, BMI, waist circumference and percentage of body fat were increased in TSH >2.5 group compared to TSH ≤2.5 group in women. However, plasma lipids showed no significant differences. In males all the parameters showed no significant differences between two groups. Serum TSH was significantly correlated with body weight, BMI, waist circumference and percentage of body fat after adjustment for age in females. Multiple linear regression analysis revealed that percentage of body fat and BMI contributed significantly to the variance of TSH. Serum TSH level was significantly higher in nonalcoholic fatty liver group than in normal group in females. Multiple logistic regression analysis showed that TSH level was not the independent risk factor of NAFLD. Taken together the data suggest that serum TSH in normal range is significantly correlated with BMI and percentage of body fat in females. And the change of TSH level would not influence the prevalence of NAFLD.
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ObjectiveTo investigate the effects of adult catch-up growth on insulin sensitivity and stress in rats, as well as the probable mechanism of insulin resistance. MethodsMale Sprague-Dawley rats were divided into 6 groups:caloric restriction group ( R4, caloric restriction for 4 weeks) and normal controls for 4 weeks ( NC4 ) ; catchup growth group refed with normal chow( RN4, refeeding for 4 weeks after caloric restriction for 4 weeks), catch-up growth group refed with high-fat diet( RH4, refeeding for 4 weeks after caloric restriction for 4 weeks ), normal chow (NC8) or high-fat diet( HF8 ) controls for 8 weeks. The animal model of catch-up growth was devoloped by way of refeeding after caloric restriction as scheduled. The glucose infusion rate( GIR ), 2-deoxyglucose uptake and insulinsitmulated insulin signaling in skeletal muscle during hyperinsulinemic-euglycemic clamp, plasma corticosterone, and 11β-hydroxysteroid dehydrogenase type 1 ( 11β-HSD1 ) mRNA expression level in skeletal muscle were determined.ResultsAfter caloric restriction for 4 weeks, plasma corticosterone and 1 1 β-HSD1 mRNA expression in skeletal muscle were significantly higher in R4 group compared with NC4 group( both P＜0. 05 ), but there were no differences in 2-deoxyglucose uptake and Ser473 phosphorylation of Akt in skeletal muscle between two groups. The plasma corticosterone and 11β-HSD1 mRNA expression in skeletal muscle in RN4 group were significantly higher than those in NC8 group, and were higher in RH4 group than those in NC8 and HF8 groups; while the 2-deoxyglucose uptake and insulin-stimulated Ser473 phosphorylation of Akt in skeletal muscle during the clamp in RN4 were remarkably lower than those in NC8 group, and were lower in RH4 than those in NC8, HF8, and RN4 groups (all P ＜ 0. 05 ).ConctusionsCatch-up growth rats refed with normal chow or high-fat diet are characterized by significant insulin resistance and stress in the whole body and skeletal muscle. These changes are more evident in catch-up growth rats refed with high-fat diet. The interaction of increased stress and diet might be of utmost importance in the etiology of insulin resistance in catch-up growth animals.
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Wistar rats(n=24) were divided into normal control group(NC), food restriction group(FR), and catch-up group(RN). Serum glucose,lipids, gastrin, the ratio of visceral fat to body fat, adipocyte CCK2R mRNA and protein levels were determined. Compared with NC group, FR rats had lower serum gastrin and visceral fat formation. The adipocyte CCK2R mRNA and protein levels of FR rats were lower than those of NC rats. Serum gastrin level of RN rats was higher than those of FR and NC rats(P＜0.05). The ratio of visceral fat to body fat in RN rats increased compared with FR rats and was close to that of NC rats. The adipocyte CCK2R mRNA and protein levels of RN rats were higher than those of FR and NC rats. Gastrin and its receptor pathway possibly play a role in the mechanism of visceral fat accumulation in catch-up rats.
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Caloric restriction(CR)remains the most robust one in all possible aging interventions,while the utility of it in humans would be difficult.CR mimeties(CRM)could mimic CR effects without changing calorie intake and have a promising prospect of application.CRM include glyeolysis inhibiter,insulin-like growth factorI,insulin sensitizer,sirtuins,PPAR agonists,and lipid-regulating drugs.
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dation, transiently inercasod food efficiency,and a faster growth rate of visceral adipose tissue versus body weight after nutritional rehabilitation. These findings are consistent with the characteristics of human catch-up growth.
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Objective To observe the glucose utilization in adipose tissue and skeletal muscle during catch-up growth, and to explore the mechanism of catch-up growth of adipose tissue. Methods Male Wistar rats were randomly divide into normal control group(NC)and catch-up group(RN). Rats in RN group received 50%of food consumed by NC group for 4 weeks, then were re-fed spontaneously as the rats in NC group. In the end of the fifth week(NC1 group and RN1 group)and the sixth week(NC2 group and RN2 group), the experiment was performed. [3]-2-deoxy-glucose was used for detecting the glucose uptake rate. RT-PCR and Western-blot were used for detecting the levels of mRNA and membrane protein of glucose transporter-4(Glut4). Results The glucose uptake rates in adipose tissue and skeletal muscle of RN1 group increased by 189.6%(P<0.01)and reduced by 36.5%(P<0.05)respectively, as compared with NC1 group. After 2 weeks of catch-up growth, the glucose uptake rates in adipose tissue of RN2 group increased by 157.3%(P<0.01)and decreased by 41.5%(P<0.05) in skeletal muscle as compared with NC2 group. However. no significant difference in Glut4 mRNA levels in muscle or in adipose tissue between NC and RN groups were found. The membrane protein of GIut4 after insulin-stimulating in RN1 group and RN2 group reduced by about 46.5%(P<0.01)and 32.1%(P<0.05)in muscle and increased by 116.5%(P<0.01)and 89.9%(P<0.01)in adipose tissue respectively. Conclusion There exists the redistribution of glucose from skeletal muscle to adipose tissue during the early stage of catch-up growth, which results in the catch-up growth of adipose tissue. This change is induced by the tissue-specific alteration of insulin-stimulated Glut4 protein translocation.