The effect of PPARγ agonist on SGLT2 and glucagon expressions in alpha cells under hyperglycemia.

BACKGROUND: Although sodium glucose cotransporter 2 (SGLT2) inhibitors have many beneficial effects for type 2 diabetes, including decreased cardiovascular death, recent reports that they increased glucagon through SGLT2 inhibition raised some concern. Troglitazone, Peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, was reported to increase SGLT2 in renal proximal tubule cells, but its role on pancreatic alpha cells have not been reported. We investigated the effect of troglitazone on SGLT2 expression in alpha cells and subsequent glucagon regulation in hyperglycemia. METHODS: An Alpha TC1-6 cell line was cultured in control (5 mM) or hyperglycemia (HG, 15 mM) for 72 h. We applied troglitazone with or without PPARγ antagonist (GW9662 10 µM). To investigate the involvement of PI3K/Akt pathway, we applied troglitazone with or without Wortmanin. We measured sodium glucose transporter 2 (SGLT2) and glucagon (GCG) mRNA and protein expression. PPAR gamma, PI3K and Akt protein were also measured. RESULTS: Exposure of alpha TC cells to HG for 72 h increased glucagon mRNA and protein expression. HG decreased SGLT2 mRNA and protein expression. Troglitazone significantly reversed HG-induced reduction of SGLT2 expression and increase of glucagon secretion. PPARγ antagonist (GW9662 10 µM) decreased the expression of SGLT2 and increased glucagon as HG did. Hyperglycemia increased PI3K and pAkt expression in alpha cells. Wortmanin (PI3K inhibitor, 1 µM) reversed HG-induced SGLT2 decrease and glucagon increase. Troglitazone treatment decreased PI3K and pAkt expression in HG. CONCLUSION: In conclusion, PPARγ agonist, troglitazone improved glucose transport SGLT2 dysfunction and subsequent glucagon dysregulation in alpha cell under hyperglycemia. Those effects were through the involvement of PI3K/pAkt signaling pathway. This study may add one more reason for the ideal combination of PPARγ agonist and SGLT2 inhibitor in clinical practice.

Percentage of the population at high risk of osteoporotic fracture in South Korea: analysis of the 2010 Fifth Korean National Health and Nutrition Examination survey data.

UNLABELLED: Osteoporosis and high-risk osteopenia (high-risk of osteoporotic fractures) are highly prevalent in South Korean postmenopausal women and men aged 50 years and over. INTRODUCTION: This study determined the percentages of the population at high risk of osteoporotic fractures according to the World Health Organization (WHO) criteria and the Fracture Risk Assessment (FRAX) model. METHODS: Data collected from the 2010 Fifth Korean National Health and Nutrition Examination Survey, a cross-sectional survey of the general South Korean general population, were analyzed. The percentages of the population with high-risk osteopenia according to the US National Osteoporosis Foundation (NOF) and Japanese treatment guidelines were subsequently determined and compared. RESULTS: Based on the WHO criteria and FRAX model, 37.7% of the menopausal women and 12.7% of the men aged 50 years and older are at high risk of osteoporotic fracture. According to the Japanese and NOF guidelines, 10.9 (10.6% of men and 11.2% of women) and 10.7% (10.6% of men and 10.9% of women), respectively, of the study population with osteopenia are at high risk of fracture. By age group, 49.3% of Korean women aged 55 years and older, 67.7% of Korean women aged 65 years and older, and 33.5% of Korean men aged 75 years and older are at high risk. CONCLUSION: As a very large percentage of the South Korean postmenopausal population has osteoporosis or high-risk osteopenia, greater effort at identifying and treating this population should be expended to prevent osteoporotic fracture.

A decision tree-based approach for identifying urban-rural differences in metabolic syndrome risk factors in the adult Korean population.

AIM: The purpose of this study was to explore the difference in the pattern of metabolic syndrome (MetS) in urban and rural populations in Korea using data mining techniques. SUBJECTS AND METHODS: In total, 1013 adults >30 yr of age from urban (184 males and 313 females) and rural districts (211 males and 305 females) were recruited from Gyeongsangnam-do, Korea. Modified National Cholesterol Education Program Adult Treatment Panel III criteria were used to identify individuals with MetS. We applied a decision tree analysis to elucidate the differences in the clustering of MetS components between the urban and rural populations. RESULTS: The prevalence of MetS was 33.2% and 35.2% in urban and rural districts, respectively (p=0.598). The decision-tree approach revealed that the combination of high serum triglycerides (TG) + high systolic blood pressure (SBP), high TG + low HDL cholesterol, and high waist circumference (WC) + high SBP + high fasting plasma glucose (FPG) were strong predictors of MetS in the urban population, whereas the combination of TG + SBP + WC and SBP + WC + FPG showed high positive predictive value for the presence of MetS in the rural population. CONCLUSIONS: Although no significant difference was found for the prevalence of MetS between the two populations, the differences in the clustering pattern of MetS components in urban and rural districts in Korea were identified by decision tree analysis. Our findings may serve as a basis to design necessary population-based intervention programs for prevention and progression of MetS and its complications in Korea.

The association between the ratio of visceral fat to thigh muscle area and metabolic syndrome: the Korean Sarcopenic Obesity Study (KSOS).

OBJECTIVE: A relationship between visceral fat accumulation and metabolic syndrome (MetS) has been established. However, the effect of a relative increase in visceral fat and a decrease in muscle mass on metabolic disorders has not been investigated. The aim of the present study was to examine the association between the ratio of visceral fat to thigh muscle area (VMR) and MetS in Korean adults. STUDY SUBJECT/MEASUREMENTS: A total of 264 age-and gender-matched subjects recruited from the Korean Sarcopenic Obesity Study (KSOS), an ongoing prospective observational cohort study, were categorized into four groups based on their body mass index (BMI) and VMR. We measured visceral fat area and thigh muscle area using computed tomography. RESULTS: Subjects with MetS showed a significantly higher VMR than those without MetS. In both obese and nonobese groups, the subjects with a higher VMR had a higher prevalence of MetS than those in the lower VMR groups. VMR was significantly related to components of the metabolic syndrome, especially in women, and was positively correlated with a number of MetS components in both men and women. In multiple logistic regression analysis, the odds ratio for MetS was 6·72 (highest vs lowest quartile, 95% confidence interval, 1·60-28·14) after an adjustment of potential confounders, including BMI and waist-to-hip ratio. CONCLUSION: VMR is significantly increased in subjects with MetS and independently associated with MetS. These results suggest that the VMR may be a potential indicator for MetS risk in Korean adults.

Prevalence of sarcopenia and sarcopenic obesity in Korean adults: the Korean sarcopenic obesity study.

OBJECTIVES: To examine the prevalence of sarcopenia and sarcopenic obesity (SO) as defined by different indices, including appendicular skeletal muscle mass (ASM)/height(2), skeletal muscle mass index (SMI) and residuals for Korean adults, and to explore the association between SO and metabolic syndrome. METHODS: Our study sample included 526 participants (328 women, 198 men) for whom complete data on body composition were collected using available dual X-ray absorptiometry. Modified National Cholesterol Education Program Adult Treatment Panel III criteria were used to identify the individuals with metabolic syndrome. RESULTS: The prevalence of sarcopenia and SO is higher in older adults. Using two s.d. of ASM/height(2) below reference values from young, healthy adults as a definition of sarcopenia, the prevalence of sarcopenia and SO was 6.3% and 1.3% in older (> or =60 years) men and 4.1% and 0.8% in older women, respectively. The prevalence of sarcopenia using the residuals method was 15.4% in older men and 22.3% in older women. In addition, using two s.d. of SMI, the prevalence of sarcopenia and SO was 5.1% and 5.1%, respectively, in older men and 14.2% and 12.5%, respectively, in older women. Among women, SO subjects defined by the SMI had three times the risk of metabolic syndrome (odds ratios (OR)=3.24, 95% confidence interval (CI)=1.21-8.66) and non-sarcopenic obese subjects had approximately twice the risk of metabolic syndrome (OR=2.17, 95% CI=1.22-3.88) compared with normal subjects. Similar trends were observed in men. CONCLUSION: The prevalence and cutoff values of sarcopenia and SO in the Korean population were evaluated using different methods. Among the different indices of sarcopenia and SO, SO only defined using the SMI was associated with the risk of metabolic syndrome. As the Korean population gets older and more obese, the problematics of SO need to be elucidated.

Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women.

OBJECTIVE: Lipocalin family proteins, including adipocyte fatty acid-binding protein (A-FABP), lipocalin-2 and retinol-binding protein 4 (RBP4), have recently been identified as novel adipokines associated with obesity, type 2 diabetes and the metabolic syndrome. We have evaluated the effect of exercise training on lipocalin family proteins and inflammatory markers. STUDY SUBJECTS: Thirty obese Korean women and 15 age-matched nonobese control subjects were studied. DESIGN: Concentrations of the lipocalin family proteins were compared between obese and nonobese women and were evaluated before and 3 months after an exercise programme consisting of aerobic exercise (45 min/session, 300 kcal/day) and muscle strength training (20 min/session, 100 kcal/day) five times a week. RESULTS: Obese women exhibited higher A-FABP levels compared to nonobese women (21.4 +/- 6.4 microg/l vs. 13.6 +/- 4.4 microg/l, P < 0.001). However, neither lipocalin-2 nor RBP4 levels were significantly different between the two groups, although the difference in lipocalin-2 was marginally significant (P = 0.054). Circulating A-FABP levels were significantly associated with body mass index (BMI), waist circumference, triglyceride, alanine aminotransferase (ALT), lipocalin-2 and high-sensitivity C-reactive protein (hsCRP) levels. After 3 months of the exercise training programme, serum A-FABP levels decreased significantly from 21.4 +/- 6.4 microg/l to 19.3 +/- 6.8 microg/l (P = 0.038), along with a reduction in weight, BMI, waist circumference, fasting glucose and total cholesterol levels. There was no significant change in the lipocalin-2 and RBP4 levels, although IL-6 levels increased after the exercise programme. CONCLUSION: Exercise training with weight loss induced a significant reduction in circulating A-FABP levels in obese Korean women.

A Ubiquitous Chronic Disease Care system using cellular phones and the internet.

AIMS: The rapidly increasing prevalence of chronic diseases is an important challenge to healthcare systems worldwide. To improve the quality and efficiency of chronic disease care, we investigated the effectiveness and applicability of the Ubiquitous Chronic Disease Care (UCDC) system using cellular phones and the internet for overweight patients with both Type 2 diabetes and hypertension. METHODS: We conducted a randomized, controlled clinical trial over 3 months that included 123 patients at a university hospital and a community public health centre. RESULTS: After 12 weeks, there were significant improvements in HbA(1c) in the intervention group (7.6 +/- 0.9% to 7.1 +/- 0.8%, P < 0.001) compared with the control group (7.4 +/- 0.9% to 7.6 +/- 1.0%, P = 0.03). Furthermore, we observed a significant reduction in systolic and diastolic blood pressure, as well as improvements in total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels in the intervention group. Furthermore, there was a significant increase in adiponectin levels in the intervention group compared with the control group, although high-sensitivity C-reactive protein and interleukin-6 levels did not change in either group. CONCLUSIONS: The novel UCDC system presented in this paper improved multiple metabolic parameters simultaneously in overweight patients with both Type 2 diabetes and hypertension.

Association of extracellular cleavage of E-cadherin mediated by MMP-7 with HGF-induced in vitro invasion in human stomach cancer cells.

BACKGROUND: Proteolytic shedding of the ectodomain of a variety of transmembrane proteins, including cell-to-cell adhesion molecules, has been observed in solid cancers. We have investigated whether extracellular cleavage of E-cadherin mediated by matrix metalloproteinase-7 (MMP-7) is involved in hepatocyte growth factor (HGF) induced in vitro invasion in stomach cancer cells. METHODS: The effects of HGF on the expression of E-cadherin/beta-catenin and MMP-7 at both the protein and mRNA levels were assessed in stomach cancer cells, NUGC-3 and MKN-28, and in cells in which the expression of MMP-7 was downregulated by transfection with a MMP-7 short hairpin RNA plasmid. RESULTS: Treatment with HGF increased the extracellular cleavage of E-cadherin and the release of MMP-7 and reduced the level of E-cadherin in a dose- and time-dependent manner. HGF treatment repressed the phosphorylation of beta-catenin in a Triton-soluble fraction, but enhanced this phosphorylation in a Triton-insoluble fraction. The association of E-cadherin with beta-catenin was decreased by HGF treatment in the Triton-soluble fraction. In addition, treatment of MMP-7 short hairpin RNA transfected NUGC-3 cells with HGF resulted in no extracellular cleavage of E-cadherin and also decreased the in vitro cell invasion. CONCLUSIONS: These results suggest that incubation with HGF mediated the release of MMP-7, resulting in extracellular cleavage of E-cadherin from stomach cancer cells. This might be a key mechanism in HGF-induced in vitro invasion and metastasis.

Associations of Low Muscle Mass and the Metabolic Syndrome in Caucasian and Asian Middle-aged and Older Adults.

OBJECTIVE: Age-related declines in skeletal muscle mass may confer significant metabolic consequences for older adults. Associations of low muscle mass and metabolic syndrome (MetS) in Caucasians, and comparisons with associations observed in Asian populations, have not been reported. We examined associations of low muscle mass and metabolic syndrome (MetS) in Asian and Caucasian middle-aged and older men and women using criteria for low muscle mass. DESIGN, SETTING AND PARTICIPANTS: Two population-based studies of Australian (Tasmanian Older Adult Cohort Study; TASOAC; N=1005) and Korean (Korean Sarcopenic Obesity Study; KSOS; N=376) community-dwelling adults, mean age 62 and 58 years, respectively. MEASUREMENTS: Appendicular lean mass (aLM) determined by dual-energy X-ray absorptiometry and normalised to height squared (aLM/Ht2), weight (aLM/Wt) or body mass index (aLM/BMI). Participants in the lowest sex-specific 20% for aLM measures were defined as having low muscle mass. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: Although Australians demonstrated generally unfavourable anthropometric and metabolic characteristics compared to Koreans, prevalence of MetS was similar (29.5% in Australians and 31.4% in Koreans, respectively). Low aLM/Ht2 was associated with significantly reduced likelihood of MetS in both Australians (OR: 0.30, 95% CI 0.19 - 0.46) and Koreans (OR: 0.31, 95% CI 0.16 - 0.62). Conversely, low aLM/BMI was associated with increased odds for MetS in Australians (OR: 1.78, 95% CI 1.12 - 2.84), but not Koreans (OR: 1.33, 95% CI = 0.67 - 2.64). CONCLUSION: Low aLM/BMI is associated with significantly increased likelihood of MetS in Australian adults, but not Koreans, suggesting potential differences in effects of low muscle mass relative to body mass on cardiometabolic health in Caucasian and Asian middle-aged and older adults. Low muscle mass relative to height is associated with reduced likelihood of MetS in both populations.

[The role of antibody functional activity in the protection of people against influenza]. / Rol' funktsional'noi aktivnosti antitel v zashchishchennosti liudei ot grippa.

Indices of the functional activity of specific serum antibodies (IFAA) before and after outbreaks of influenza A (H3N2) and B were determined in 164 subjects of 18-20 years of age from the military communities observed in 1987-1988. The IFAA were calculated on the basis of kinetic HI tests followed by computer processing according to the program developed by the authors. The IFAA were found to indicate the protection of human subjects against influenza, reflecting the state of resistance to influenza more exactly than antibody titres. High initial IFAA correlated with lower severity of influenza infection. The IFAA to the same strain may differ significantly in individual subjects. In patients with influenza the time course of antibody titres did not coincide with dynamic changes in IFAA.

[Indicators of collective immunity to influenza depending on the blood group and sex of the population]. / Pokazateli kollektivnogo immuniteta k grippu v zavisimosti ot gruppi krovi i pola obsleduemogo naseleniia.

Immunological investigations of the time course of serum anti-HA and anti-NA antibodies against influenza A and B viruses in the female and male population with blood groups 0(I), A(II), B(III), and AB(IV) were carried out for several months. The persons with the blood group AB (IV) were shown to be most sensitive to influenza A and B. They were affected by the epidemic virus earlier and more severely than those with the other blood groups. A special method is proposed for prediction of the etiology of the forthcoming epidemic. A correlation between blood groups and titres of anti-HA but not anti-NA antibodies was observed. The view on the lack of the genetic factor influence on the affliction with influenza and antibody response in persons of different sexes is substantiated.

[Regularities of formation in a general population of serum antibodies to previously circulated influenza A viruses]. / Zakonomernosti obrazovaniia u naseleniia syvorotochnykh antitel k ranee tsirkulirovavshim virusam grippa A.

The spectrum of antibody production against hemagglutinin of all known influenza A virus serotypes after influenza A (H3N2) infection in persons of all age groups (from 1 month to 72 years) was analysed to investigated the regularities of accumulation of antibodies against influenza A viruses gone out of circulation. For the same purpose, a long-term (many years) longitudinal analysis of serum anti-HA antibody levels against "old" influenza A (HSW1N1), A (H0N1), A (H1N1), A (H2N2), and A (H3N2) viruses was carried out in children and adults of various age groups in 6 cities of different geographical regions of the country. Based on the results of the study, the concept of the "original antigenic sin" is analysed critically, and a new original concept on the regularities of antibody genesis against previously prevalent influenza A viruses and the factors affecting this process has been formulated.

[Immunoenzyme analysis of post-vaccination secretory immunity to influenza A and B viruses using a manufactured monoclonal immunoenzyme test system]. / Izuchenie v immunofermentnom analize postvaktsinal'nogo sekretornogo immuniteta k virusam grippa A i B s pomoshch'iu razrabotannoi monoklonal'noi immunofermentnoi test-sistemy.

The formation of postvaccinal secretory immunity to influenza A and B viruses was studied by a new monoclonal enzyme immunoassay test system for measuring specific secretory IgA in young people vaccinated with live cold-adapted vaccines (LCAV) intranasally and with inactivated commercial centrifuged influenza vaccine (IIV) parenterally, intranasally, and orally. Secretory IgA most intensively accumulated in subjects intranasally vaccinated with LCAV, less so in subjects vaccinated with IIV intranasally and orally, and just negligibly in those vaccinated with IIV parenterally. In vaccinees immunized with LCAV intranasally the intensity of immune secretory response depended on the initial concentrations of specific IgA before vaccination. Intranasal administration of LCAV in the presence of high concentrations of secretory IgA led in some subjects either to a decrease in the incidence of conversions or to a 2-8-fold drop of their initial titers. Parenteral injection of IIV caused the most expressed suppression of the immune response in the secretory immunity system. Use of biological stimulant adaptogen increased 2.2 times the incidence of conversions of secretory IgA in subjects intranasally vaccinated with LCAV.

[Antibody functional activity in immunization with influenza vaccines]. / Funktsional'naia aktivnost' antitel pri immunizatsii grippoznymi vaktsinami.

The functional activity of serum antibody had been shown previously to reflect the state of resistance to influenza more accurately than antibody concentration. The functional activity of antibodies in the vaccination process was studied. The immune response to influenza antigens was found to be accompanied by an increase in the functional activity of antibodies, the intensity of this increase was the highest in natural influenza infection, moderate after administration of live vaccines and the least after immunization with inactivated preparations. The vaccine strains may differ significantly in their capacity to stimulate antibody with high functional activity. The quantitative parameters of the functional activity of antibody are directly related to the antigen dose and frequency of antigenic stimulation.

[The use of saliva for study in the immunoenzyme analysis of postvaccinal and postinfectious immunity to influenza]. / Ispol'zovanie sliuny dlia izucheniia v immunofermentnom analize postvaktsinal'nogo i postinfektsionnogo immuniteta k grippu.

Paired specimens of blood sera, upper respiratory tract secretions, and saliva from healthy, influenza-infected, and live influenza trivaccine-immunized humans were tested in parallel by HI tests and enzyme immunoassay (EIA). The resulting comparative data suggest that determination by EIA of specific secretory IgA in the saliva may be recommended as an independent test for large-scale influenza diagnosis, evaluation of the immune status of people, and trials of influenza vaccines. By immunologic parameters, this method is not inferior to the standard ones. At the same time its advantages include simplicity and readily available large volumes of saliva even from children as well as no necessity to bleed subjects to be examined.