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Metabolic Consequences (metabolic + consequence)
Selected AbstractsMetabolic consequences of pancreatic systemic or portal venous drainage in simultaneous pancreas-kidney transplant recipientsDIABETIC MEDICINE, Issue 6 2006P. Petruzzo Abstract Aims The aim was to investigate pancreatic B-cell function and insulin sensitivity in simultaneous pancreas-kidney (SPK) recipients with systemic or portal venous drained pancreas allograft using simple and easy tests. Methods The study included 44 patients with Type 1 diabetes and end-stage renal disease who had undergone SPK transplantation: 20 recipients received a pancreas allograft with systemic venous drainage (S-SPK) and 24 with portal venous drainage (P-SPK). We studied only recipients with functioning grafts, with normal serum glucose, HbA1c and serum creatinine values, on a stable drug regimen. The subjects were studied at 6, 12, 24, 36, 48 and 60 months after transplantation. Insulin sensitivity and B-cell function indices were derived from blood samples and oral glucose tolerance tests. Results All patients from both groups had normal fasting glucose, body mass index and HbA1c values by selection. The homeostatic model (HOMA) ,-cell index was significantly lower in P-SPK recipients at several points of the follow-up. HOMA-IR was significantly higher in S-SPK recipients at 6 and 24 months after transplantation and was positively correlated with fasting insulin values, but never exceeded 3.2. There was no significant difference in QUICKI index values between the two groups. Although all patients from both groups always had normal glucose tolerance, the area under the insulin curve was higher in the S-SPK group. Cholesterol, low-density lipoprotein-cholesterol and triglycerides were higher in the P-SPK group. Conclusions The results suggest sustained long-term endocrine function in both groups and show that portal venous drainage does not offer major metabolic advantages. [source] Alcoholic skeletal muscle myopathy: definitions, features, contribution of neuropathy, impact and diagnosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2001V. R. Preedy Alcohol misusers frequently have difficulties in gait, and various muscle symptoms such as cramps, local pain and reduced muscle mass. These symptoms are common in alcoholic patients and have previously been ascribed as neuropathological in origin. However, biochemical lesions and/or the presence of a defined myopathy occur in alcoholics as a direct consequence of alcohol misuse. The myopathy occurs independently of peripheral neuropathy, malnutrition and overt liver disease. Chronic alcoholic myopathy is characterized by selective atrophy of Type II fibres and the entire muscle mass may be reduced by up to 30%. This myopathy is arguably the most prevalent skeletal muscle disorder in the Western Hemisphere and occurs in approximately 50% of alcohol misusers. Alcohol and acetaldehyde are potent inhibitors of muscle protein synthesis, and both contractile and non-contractile proteins are affected by acute and chronic alcohol dosage. Muscle RNA is also reduced by mechanisms involving increased RNase activities. In general, muscle protease activities are either reduced or unaltered, although markers of muscle membrane damage are increased which may be related to injury by reactive oxygen species. This supposition is supported by the observation that in the UK, , -tocopherol status is poor in myopathic alcoholics. Reduced , -tocopherol may pre-dispose the muscle to metabolic injury. However, experimental , -tocopherol supplementation is ineffective in preventing ethanol-induced lesions in muscle as defined by reduced rates of protein synthesis and in Spanish alcoholics with myopathy, there is no evidence of impaired , -tocopherol status. In conclusion, by a complex series of mechanisms, alcohol adversely affects skeletal muscle. In addition to the mechanical changes to muscle, there are important metabolic consequences, by virtue of the fact that skeletal muscle is 40% of body mass and an important contributor to whole-body protein turnover. [source] Disturbed hepatic carbohydrate management during high metabolic demand in medium-chain acyl,CoA dehydrogenase (MCAD),deficient mice,HEPATOLOGY, Issue 6 2008Hilde Herrema Medium-chain acyl,coenzyme A (CoA) dehydrogenase (MCAD) catalyzes crucial steps in mitochondrial fatty acid oxidation, a process that is of key relevance for maintenance of energy homeostasis, especially during high metabolic demand. To gain insight into the metabolic consequences of MCAD deficiency under these conditions, we compared hepatic carbohydrate metabolism in vivo in wild-type and MCAD,/, mice during fasting and during a lipopolysaccharide (LPS)-induced acute phase response (APR). MCAD,/, mice did not become more hypoglycemic on fasting or during the APR than wild-type mice did. Nevertheless, microarray analyses revealed increased hepatic peroxisome proliferator-activated receptor gamma coactivator-1, (Pgc-1,) and decreased peroxisome proliferator-activated receptor alpha (Ppar ,) and pyruvate dehydrogenase kinase 4 (Pdk4) expression in MCAD,/, mice in both conditions, suggesting altered control of hepatic glucose metabolism. Quantitative flux measurements revealed that the de novo synthesis of glucose-6-phosphate (G6P) was not affected on fasting in MCAD,/, mice. During the APR, however, this flux was significantly decreased (,20%) in MCAD,/, mice compared with wild-type mice. Remarkably, newly formed G6P was preferentially directed toward glycogen in MCAD,/, mice under both conditions. Together with diminished de novo synthesis of G6P, this led to a decreased hepatic glucose output during the APR in MCAD,/, mice; de novo synthesis of G6P and hepatic glucose output were maintained in wild-type mice under both conditions. APR-associated hypoglycemia, which was observed in wild-type mice as well as MCAD,/, mice, was mainly due to enhanced peripheral glucose uptake. Conclusion: Our data demonstrate that MCAD deficiency in mice leads to specific changes in hepatic carbohydrate management on exposure to metabolic stress. This deficiency, however, does not lead to reduced de novo synthesis of G6P during fasting alone, which may be due to the existence of compensatory mechanisms or limited rate control of MCAD in murine mitochondrial fatty acid oxidation. (HEPATOLOGY 2008.) [source] SIRT6 protects against pathological damage caused by diet-induced obesityAGING CELL, Issue 2 2010Yariv Kanfi Summary The NAD+-dependent SIRT6 deacetylase is a therapeutic candidate against the emerging metabolic syndrome epidemic. SIRT6, whose deficiency in mice results in premature aging phenotypes and metabolic defects, was implicated in a calorie restriction response that showed an opposite set of phenotypes from the metabolic syndrome. To explore the role of SIRT6 in metabolic stress, wild type and transgenic (TG) mice overexpressing SIRT6 were fed a high fat diet. In comparison to their wild-type littermates, SIRT6 TG mice accumulated significantly less visceral fat, LDL-cholesterol, and triglycerides. TG mice displayed enhanced glucose tolerance along with increased glucose-stimulated insulin secretion. Gene expression analysis of adipose tissue revealed that the positive effect of SIRT6 overexpression is associated with down regulation of a selective set of peroxisome proliferator-activated receptor-responsive genes, and genes associated with lipid storage, such as angiopoietin-like protein 4, adipocyte fatty acid-binding protein, and diacylglycerol acyltransferase 1, which were suggested as potential targets for drugs to control metabolic syndrome. These results demonstrate a protective role for SIRT6 against the metabolic consequences of diet-induced obesity and suggest a potentially beneficial effect of SIRT6 activation on age-related metabolic diseases. [source] Comparison of the metabolic and economic consequences of long-term treatment of schizophrenia using ziprasidone, olanzapine, quetiapine and risperidone in Canada: a cost-effectiveness analysisJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 4 2010Roger S. McIntyre MD FRCPC Abstract Rationale, aims and objectives, Second-generation antipsychotic agents have varying propensities to cause weight gain, elevated lipid levels and associated long-term complications. This study evaluates the cost-effectiveness of four second-generation antipsychotic agents used in Canada for the treatment of schizophrenia (ziprasidone, olanzapine, quetiapine, risperidone) with a focus on their long-term metabolic consequences. Method, Using data from the Clinical Antipsychotic Trials of Intervention Effectiveness Study, a semi-Markov model was developed to predict the incidence and associated costs of type 2 diabetes, cardiovascular complications (e.g. angina, myocardial infarction, stroke, cardiovascular disease death), and acute psychiatric hospitalizations in patients with chronic schizophrenia treated over 5 years. Incremental costs per quality-adjusted life year (QALY) gained were calculated from the perspective of the Canadian provincial ministries of health. Scenario and probabilistic sensitivity analyses were performed. Results, The total average cost of treatment with ziprasidone was $25 301 versus $28 563 with olanzapine, $26 233 with quetiapine and $21 831 with risperidone. Ziprasidone had the lowest predicted number of type 2 diabetes cases and cardiovascular disease events, and the highest QALY gains. Patients receiving quetiapine had the highest predicted number of hospitalizations. Ziprasidone was less costly and resulted in more QALYs compared with olanzapine and quetiapine. Compared with risperidone, ziprasidone was more costly and had higher QALYs, with an incremental cost per QALY gained of $218 060. Conclusion, Compared with olanzapine and quetiapine, ziprasidone produced savings to the health care system. Although ziprasidone generated incremental expenditures versus risperidone, it resulted in more QALYs. Based on this analysis, ziprasidone treatment possesses cost and therapeutic advantages compared with olanzapine and quetiapine. [source] Alterations in Brain Glucose Utilization Accompanying Elevations in Blood Ethanol and Acetate Concentrations in the RatALCOHOLISM, Issue 2 2010Robert J. Pawlosky Background:, Previous studies in humans have shown that alcohol consumption decreased the rate of brain glucose utilization. We investigated whether the major metabolite of ethanol, acetate, could account for this observation by providing an alternate to glucose as an energy substrate for brain and the metabolic consequences of that shift. Methods:, Rats were infused with solutions of sodium acetate, ethanol, or saline containing 13C-2-glucose as a tracer elevating the blood ethanol (BEC) and blood acetate (BAcC) concentrations. After an hour, blood was sampled and the brains of animals were removed by freeze blowing. Tissue samples were analyzed for the intermediates of glucose metabolism, Krebs' cycle, acyl-coenzyme A (CoA) compounds, and amino acids. Results:, Mean peak BEC and BAcC were approximately 25 and 0.8 mM, respectively, in ethanol-infused animals. Peak blood BAcC increased to 12 mM in acetate-infused animals. Both ethanol and acetate infused animals had a lower uptake of 13C-glucose into the brain compared to controls and the concentration of brain 13C-glucose-6-phosphate varied inversely with the BAcC. There were higher concentrations of brain malonyl-CoA and somewhat lower levels of free Mg2+ in ethanol-treated animals compared to saline controls. In acetate-infused animals the concentrations of brain lactate, ,-ketoglutarate, and fumarate were higher. Moreover, the free cytosolic [NAD+]/[NADH] was lower, the free mitochondrial [NAD+]/[NADH] and [CoQ]/[CoQH2] were oxidized and the ,G, of ATP lowered by acetate infusion from ,61.4 kJ to ,59.9 kJ/mol. Conclusions:, Animals with elevated levels of blood ethanol or acetate had decreased 13C-glucose uptake into the brain. In acetate-infused animals elevated BAcC were associated with a decrease in 13C-glucose phosphorylation. The co-ordinate decrease in free cytosolic NAD, oxidation of mitochondrial NAD and Q couples and the decrease in ,G, of ATP was similar to administration of uncoupling agents indicating that the metabolism of acetate in brain caused the mitochondrial voltage dependent pore to form. [source] In vitro determination of digestible and unavailable protein in edible seaweedsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 15 2002Isabel Gońi Abstract Edible seaweeds are considered a complementary source of food protein for human and animal nutrition. The physiological effects of seaweed protein depend on the degree of enzymatic digestion of protein in the small intestine and bacterial fermentation in the large intestine. The objective of this work was to estimate total, digestible, fermentable and unavailable protein in some red and brown seaweeds. Brown seaweeds Fucus vesiculosus, Laminaria digitata and Undaria pinnatifida and red seaweeds Chondrus crispus and Porphyra tenera were treated with pepsin and pancreatin to separate digestible protein. Residues containing indigestible protein were inoculated for 24,h with rat caecal droppings, and protein contents were evaluated in the non-fermented residue. Protein content in the seaweeds ranged from 8.9 to 25% of dry matter. Digestible protein was the major protein fraction (69%) only in P tenera; in the other seaweeds, this fraction ranged from 15 to 45%. Significant amounts of unavailable protein were found in all samples (2,24%). The distribution of total protein among the three fractions, ie digestible, fermentable and unavailable protein, could yield information about the physiological and metabolic consequences of the intake of seaweed proteins. © 2002 Society of Chemical Industry [source] Cerebral activation by fasting induces lactate accumulation in the hypothalamusMAGNETIC RESONANCE IN MEDICINE, Issue 2 2009Inęs R. Violante Abstract Carbon-13 (13C) high-resolution magic angle spinning (HR-MAS) spectroscopy was used to investigate the neuroglial coupling mechanisms underlying appetite regulation in the brain of C57BL/6J mice metabolizing [1- 13C]glucose. Control fed or overnight fasted mice received [1- 13C]glucose (20 ,mol/g intraperitoneally [i.p.]), 15 min prior to brain fixation by focused microwaves. The hypothalamic region was dissected from the rest of the brain and 13C HR-MAS spectra were obtained from both biopsies. Fasting resulted in a significant increase in hypothalamic [3- 13C]lactate and [2- 13C],-aminobutyric acid (GABA) relative to the remaining brain. Administration of the orexigenic peptide ghrelin (0.3 nmol/g i.p.) did not increase hypothalamic [3- 13C]lactate or [2- 13C]GABA, suggesting that ghrelin signaling is not sufficient to elicit all the metabolic consequences of hypothalamic activation by fasting. Our results indicate that the hypothalamic regulation of appetite involves, in addition to the well-known neuropeptide signaling, increased neuroglial lactate shuttling and augmented GABA concentrations. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [source] Are the circumpolar inuit becoming obese?AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 2 2007T.K. Young This paper reviews the ethnographic, historical, and recent epidemiological evidence of obesity among the Inuit/Eskimo in the circumpolar region. The Inuit are clearly at higher risk for obesity than other populations globally, if "universal" measures based on body mass index (BMI) and waist circumference and criteria such as those of WHO are used. Inuit women in particular have very high mean waist circumference levels in international comparisons. Given the limited trend data, BMI-defined obesity is more common today than even as recently as three decades ago. Inuit are not immune from the health hazards associated with obesity. However, the "dose,response" curves for the impact of obesity on metabolic indicators such as plasma lipids and blood pressure are lower than in other populations. Long-term, follow-up studies are needed to determine the metabolic consequences and disease risks of different categories of obesity. At least in one respect, the higher relative sitting height among Inuit, obesity measures based on BMI may not be appropriate for the Inuit. Ultimately, it is important to go beyond simple anthropometry to more accurate determination of body composition studies, and also localization of body fat using imaging techniques such as ultrasound and computed tomography. Internationally, there is increasing recognition of the need for ethnospecific obesity criteria. Notwithstanding the need for better quality epidemiological data, there is already an urgent need for action in the design and evaluation of community-based health interventions, if the emerging epidemic of obesity and other chronic diseases are to be averted. Am. J. Hum. Biol. 19:181,189, 2007. © 2007 Wiley-Liss, Inc. [source] Protein and amino acid nutrition and metabolism in fish: current knowledge and future needsAQUACULTURE RESEARCH, Issue 3 2010Sadasivam J Kaushik Abstract Optimising the amino acid supply in tune with the requirements and improving protein utilization for body protein growth with limited impacts on the environment in terms of nutrient loads is a generic imperative in all animal production systems. With the continued high annual growth rate reported for global aquaculture, our commitments should be to make sure that this growth is indeed reflected in provision of protein of high biological value for humans. The limited availability of fish meal has led to some concerted efforts in fish meal replacement, analysing all possible physiological or metabolic consequences. The rising costs of plant feedstuffs make it necessary to strengthen our basic knowledge on amino acid availability and utilization. Regulation of muscle protein accretion has great significance with strong practical implications. In fish, despite low muscle protein synthesis rates, the efficiency of protein deposition appears to be high. Exploratory studies on amino acid flux, inter-organ distribution and particularly of muscle protein synthesis, growth and degradation and the underlying mechanisms as affected by dietary factors are warranted. Research on specific signalling pathways involved in protein synthesis and degradation have been initiated in order to elucidate the reasons for high dietary protein/amino acid supply required and their utilization. [source] Do women with polycystic ovary syndrome really have predisposition to atherosclerosis?AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2006Semra TOPCU Abstract The elastic properties of the aorta were studied in 28 women with polycystic ovary syndrome (PCOS) and in 26 regularly menstruating healthy women. In PCOS and control groups, systolic and diastolic blood pressure, aortic systolic diameter, aortic diastolic diameter, aortic distensibility, aortic stiffness index, and aortic elastic modulus were similar. It is likely that PCOS does not have any innate adverse effects on the cardiovascular system if its undesirable metabolic consequences are successfully controlled. [source] Modulation of growth hormone action by sex steroidsCLINICAL ENDOCRINOLOGY, Issue 4 2006Udo J. Meinhardt Summary Growth hormone (GH) is a major regulator of growth, somatic development and body composition. Sex steroids can act centrally by regulating GH secretion and peripherally modulating GH responsiveness. This review addresses data of potential clinical relevance on how sex steroids modulate GH secretion and action, aiming to increase the understanding of sex steroid/GH interactions and leading to improved management of patients. Sex steroids regulate GH secretion directly as well as indirectly through IGF-I modulation. Testosterone stimulates GH secretion centrally, an effect dependent on prior aromatization to oestrogen. Oestrogen stimulates GH secretion indirectly by reducing IGF-I feedback inhibition. Whether oestrogen stimulates GH secretion centrally in females is unresolved. Gonadal steroids modify the metabolic effects of GH. Testosterone amplifies GH stimulation of IGF-I, sodium retention, substrate metabolism and protein anabolism while exhibiting similar but independent actions of its own. Oestrogen attenuates GH action by inhibiting GH-regulated endocrine function of the liver. This is a concentration-dependent phenomenon that arises invariably from oral administration of therapeutic doses of oestrogen, an effect that can be avoided by using a parenteral route. This strong modulatory effect of gonadal steroids on GH responsiveness provides insights into the biological basis of sexual dimorphism in growth, development and body composition and practical information for the clinical endocrinologist. It calls for an appraisal of the diagnostic criteria for GH deficiency of GH stimulation tests, which currently are based on arbitrary cut-offs that do not take into account the shifting baseline from the changing gonadal steroid milieu. In the management of GH deficiency in the hypopituitary female, oestrogen should be administered by a nonoral route. In hypopituitary men, androgens should be replaced concurrently to maximize the benefits of GH. In the general population, the metabolic consequences of long-term treatment of women with oral oestrogen compounds, including selective oestrogen receptor modulators, are largely unknown and warrant study. [source] | |||||||||||||