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音量 5, 問題 1 (2016)

研究論文

C358A Polymorphism of the Endocannabinoid Degrading Enzyme Fatty Acid Amide Hydrolase (FAAH) Influence On Metabolic Parameters a High Protein/Low Carbohydrate versus a Standard Hypocaloric Diet

R Aller, O Izaola, R Bachiller, E Romero and DA de Luis

Background and aim: The C385A polymorphism of FAAH gene (rs324420C>A) has been associated with obesity. We investigate the role of this polymorphism on cardiovascular risk factors and weight loss secondary to a high protein/ low carbohydrate vs. a standard hypocaloric diets (1000 kcal/day) during 9 months.
Methods: A sample of 284 subjects with obesity (body mass index (BMI) >30) was enrolled. These subjects were randomly allocated to one of two diets for a period of nine months Diet S (standard protein hypocaloric diet) vs. Diet HP (high protein-low carbohydrate hypocaloric diet).
Results: After both diets and in both genotype groups (CC vs. CA+AA), body mass index (BMI), weight, fat mass, waist circumference and systolic blood pressure decreased. With the diet type HP and in non A carriers, glucose (-5.3 ± 1.2 mg/dl vs. -1.8 ± 2.1 mg/dl; p<0.05), insulin levels (-3.1 ± 1.9UI/L vs. -1.1 ± 2.0 UI/L; p<0.05), HOMA-R (-0.9 ± 0.8 units vs. -0.3 ± 1.0 units; p<0.05), total cholesterol (-11.9 ± 8.2 mg/dl vs. -0.1 ± 3.1mg/dl; p<0.05), and LDL- total cholesterol (-9.8 ± 4.2 mg/dl vs. -1.0 ± 2.1mg/dl; p<0.05) decreased. After diet S and in patients with both genotypes, total cholesterol (-6.0 ± 3.1 mg/dl vs. -10.0 ± 8.2mg/dl; ns), triglycerides (-8.1 ± 7.1 mg/dl vs. -13.1 ± 8.9 mg/dl; ns) and LDL- total cholesterol (-5.9 ± 3.0 mg/dl vs. -9.1 ± 5.8mg/dl; p<0.05) decreased.
Conclusion: Non carriers of the allele A385 of FAAH showed an improvement on insulin and HOMA-R levels with a high protein hypocaloric diet after weight loss during 9 months. A standard hypocaloric diet produced a similar improvement in lipid profile in both genotypes.

研究論文

Carbonic Anhydrase: A New Therapeutic Target for Managing Diabetes

Ibrahim S Ismail, Ameh D Amodu, Atawodi S Ene-ojoh and Umar I Alhaji

Background: Carbonic Anhydrase (CA) is a zinc metallo-enzyme that is critical to regulation of systemic acid-base homeostasis by facilitating urinary acidification. Inhibition of carbonic anhydrase results in metabolic acidosis which leads to decrease in pH.
Aim and objectives: The study aims to highlight the potential utility of erythrocyte carbonic anhydrase as therapeutic target for managing diabetes, by investigating changes of erythrocyte carbonic anhydrase activity in STZ induced diabetic rats.
Methods: Carbonic anhydrase activity was determined by the absorbance of p-nitrophenol at 345nm released from p-nitrophenyl acetate. HbA1c was determined by ion exchange method (Spectrum diagnostics). Biochemical parameters were determined by Accutrend GCT meters with cobias® test strips.
Results: The result revealed that inhibition of erythrocyte carbonic anhydrase results in significant increase in both blood lactate concentration and HbA1c level with significant reduction in blood glucose concentration. Metformin was found to reduce carbonic anhydrase activity and HbA1c level significantly and increased blood lactate concentration. The extract of Cadaba farinosa was found to reduce blood glucose concentration.
Conclusions: Inhibition of carbonic anhydrase can be associated with reduced circulating blood glucose level. Metformin may therefore reduce circulating blood glucose by inhibiting carbonic anhydrase. Increased level of HbA1c may probably be due to inhibition of erythrocyte carbonic anhydrase. Therefore Carbonic anhydrase can potentially serve as a therapeutic target for managing diabetes in combination as serving as valuable marker for lactic acidosis.

総説

Links between Autonomic Dysfunction and Metabolic Syndrome

Federica Giampetruzzi and Gabriella Garruti

The autonomic nervous system (ANS) plays a key role in the control of a number of vital functions including cardiovascular, endocrine/neurovascular, gastrointestinal, genitourinary, pupil and thermoregulatory functions. Its abnormalities have been associated with early mortality, sudden death, silent myocardial infarction, gastrointestinal diseases. The manifestation of the ANS dysfunction in several human diseases is underestimated. Evidences exist on the important role of ANS dysfunctions in different clinically relevant conditions, including diabetes mellitus, chronic functional constipation, scleroderma, thalassemia major. Beside the classical evaluation in patients with diabetes mellitus, little is known about the effects of metabolic factors on ANS dysfunction. The metabolic syndrome (MetS) includes a cluster of frequent abnormalities (impaired fasting glycaemia, dyslipidemia, arterial hypertension and increased visceral adiposity) predisposing to the atherosclerotic changes and increased cardiovascular mortality. Early signs of autonomic dysfunction are often found in subjects with MetS even in the absence of diabetes. Epidemiological studies demonstrated that diabetics display a cardiovascular risk which is twice that of sex- and age-matched non-diabetic population. Manifestations of such a high cardiovascular risk of subjects with DM are the frequent silent myocardial infarctions (MI)s of diabetics which are often due to impaired cardiovascular autonomic function. Only recently major attention has been given to the interactions between impaired glucose tolerance (IGT) and cardiovascular autonomic dysfunctions. When increased waist circumference (one of the features of the MetS) and IGT are both present, cardiovascular autonomic dysfunction also occurs. Some adipokines (e.g. adiponectin) seem to play a role in cardiovascular risk and autonomic dysfunction. This review will therefore focus on some subtle aspects linking ANS dysfunction and MetS.

研究論文

Black Tea Polyphenols Suppress Postprandial Hyperglycemia In Vivo in Mice and Inhibit α-Glucosidase Activity In Vitro

Junki Yoshida, Akiko Tateishi, Yuko Fukui, Mitsuhiro Zeida and Nobuyuki Fukui

Black tea is reported to have various beneficial effects on health. Activated charcoal-treated black tea (ACBT) did not contain catechins nor caffeine and included small amount of theaflavins (TFs). We had further fractionated ACBT to obtain black tea polymerized polyphenols (BTPP), TFs-poor fraction and TFs-rich fraction and studied in vitro and/or in vivo effect of the fractions to elucidate the effect of ACBT. Sucrose-loading test in mice showed that ACBT and BTPP at the dose of, 1000 and 560 mg/kg, respectively, suppressed the increase of blood glucose level while secretion of insulin was not affected. We found that this effect is caused by inhibition of α-glucosidase activity. BTPP contained TFs, but the content was not at all enough to explain the activity of ACBT, 1H NMR analysis of BTPP was carried and showed the existence of many benzotropolone ring containing substances as active compounds.

研究論文

The Changes of the Expression of PGC-1α and the Level of Oxidative Stress in NAFLD as well as the Effects of Metformin on NAFLD

Jian-hua Jiang, Jing Cheng, Bao Zhang, Shi-xia Guan and Li-li Hou

Purpose: The objective of this study was to determine how metformin regulates the major activator of hepatic gluconeogenesis, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and the PGC-1α controlled liver functions.

Methods: In population study, we selected 40-69 years old patients with NAFLD, 77, and 102 healthy subjects as a control group. We detect the levels of serum PGC-1α, MDA and the activity of SOD of the two groups. In vitro study, L-02 cells were treated by 20 μg/ml oleic acid to induce the NAFLD cells model. The control group added ordinary 1640 culture medium. The model group cells were cultured in the medium containing 2.5, 5, 7.5mmol/l concentrations of metformin. Used RT-PCR analysis of PGC-1α mRNA, detected the level of triglycerides in cells, measured the content of MDA and the activity of SOD.

Results: In population study, the level of MDA in the case group were increased obviously and the activity of SOD was decreased compared with the control group. There had no difference of the level of PGC-1α between the two groups. In vitro study, compared with the control groups, the level of triglyceride and the concentration of MDA in the model groups were increased and the activity of SOD as well as the expression of PGC-1α mRNA were decreased; When the final concentration of metformin is 7.5 mmol/l, the level of triglyceride and MDA were decreased as well as the activity of SOD and the expression of PGC-1α mRNA were increased compared with the model group.

Conclusion: Metformin can adjust the expression of PGC-1α and the level of oxidative stress which can decrease the fat accumulation, Our results thus identify selective modulation of hepatic PGC-1α functions as a novel mechanism involved in the therapeutic action of metformin.

研究論文

Effect of Cholecystectomy on Lipid Profile in Bangladeshi Patients with Cholelithiasis

AM Mujibul Haq, ASM Giasuddin, KA Jhuma and MAM Choudhury

Objective: As no studies were reported from Bangladesh, the present study was conducted on serum lipid profile, i.e. triglyceride TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and high density lipoproteincholesterol (HDL-C) in Bangladeshi patients with cholelithiasis

Patients and methods: A total of 44 adult patients with cholelithiasis and 30 healthy subjects as normal controls (NC) were included in the study. The blood samples were taken from fasting patients at diagnosis before cholecystectomy (Serum-I0), gall bladder bile during cholecystectomy (Bile- I0) and blood sample again after 2-3 months at follow-up (Serum-II0) and from fasting NC subjects. TG, TC, LDL-C and HDL-C were quantitated in serum and bile by standard methods using research kits from reputed companies. The results were compared statistically by ANOVA and Student’s t-test using SPSS propramme

Results: TG level was elevated in Serum- I0 , Bile- I0 and Serum- II0 of patients, being highest in Bile- I0 compared to controls (NC) (p<0.001). TG level was reduced in serum -II0 after cholecystectomy compared to Serum- I0 and Bile- I0, although it remained significantly elevated compared to controls (NC) (p<0.001). TC level was elevated in Bile- I0 compared to Serum- I0 and Serum- II0 (p<0.001). Interestingly, TC was elevated in Serum- II0 after cholecystectomy, although no significant difference was observed between NC and patients Serum- I0 (p=0.835). LDL-C levels in NC, Serum- I0 and Serum- II0 were similar (p=0.126, p=0.121), although Serum-II0 levels was elevated compared to Serum- I0 (p<0.001) and it was much elevated in Bile- I0 (p<0.001). HDL-C levels were similar (p>0.05) among NC, Serum- I0 and Serum- II0, but it was higher in Bile- I0 significantly (p<0.001).

 Conclusion: Alterations in lipid profile in cholelithiasis were significant but complex and cholecystectomy had profound impact suggesting a crucial role of gall bladder. The results were discussed accordingly.

短いコミュニケーション

The Role of Hepatokines in Cardiovascular Disease

Roever L, Resende ES and Anaisa Silva Roerver Borges

Non-alcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome, and associated with the risks of developing cardiovascular disease (CVD) and type 2 diabetes mellitus (DM2). A group of liver-derived proteins called hepatokines directly affect the pathogenesis of atherosclerosis by modulating endothelial dysfunction and infiltration of inflammatory cells. In this review we summarize the role of the representative hepatokines in the progression of CVD.

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