A pig model of childhood obesity was used to study the effects of dietary energy on body adiposity, and blood parameters associated with impaired glucose clearance. Prepubertal female pigs weaned at 21 d of age were fed control (CON), refined sugar (SUG), fat (FAT), and sugar-fat (SUGFAT) diets in a completely randomized arrangement for 16 wk. Calories from fat were 8.9% for CON, 5.6% for SUG, 35.5% for FAT and 32.3% for SUGFAT. Calories from sugar were 36.0% for SUG and 30.7% for SUGFAT. Adding fat, sugar or both to diets increased (P < 0.003) calorie intake. Percentage body fat was higher (P < 0.0001) in all treatments compared to CON, and in SUGFAT and FAT compared to SUG. Ultrasound back fat depth was positively correlated (r2 = 0.909; P < 0.001) with percentage body fat and negatively (r = 0.912; P-value ) with percentage body protein. Area under the curve (AUC) in response to oral glucose tolerance at 14 wk was higher (P < 0.03) in FAT (+14.6%) and SUGFAT (+25.5%) pigs compared to CON. Glucose AUC from sugar-fed pigs was not different (P = 0.2) from fat alone-fed pigs. Adding sugar, fat, or their combination to diets increased (P < 0.008) blood glucose and decreased (P < 0.0009) plasma insulin AUC. These data show that inclusion of fat and refined sugar in pig diets increases body adiposity and impairs glucose homeostasis and suggests that the composition of calories consumed may have different effects than simply consumption of excess of calories. / Master of Science

No description available.

Background: Canine hypothyroidism is thought to cause abnormalities in glucose homeostasis, but the effect on glucose tolerance and insulin sensitivity has not been determined to date. Hypothesis/Objectives: The purpose of the study was to investigate whether hypothyroidism has an effect on glucose tolerance and insulin sensitivity in dogs. We hypothesized that hypothyroidism causes insulin resistance. Animals: Sixteen euthyroid bitches were randomly selected and allocated into two groups. In 8 dogs, hypothyroidism was induced by administration of 1 mCi/kg I-131. Experiments were performed on non-anesthetized, fasted dogs in anestrous approximately 12 months after hypothyroidism was induced. Methods: The insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT) and minimal model analysis were used to determine basal insulin and glucose concentrations, acute insulin response to glucose (AIRg), insulin sensitivity (SI), glucose effectiveness (SG) and the disposition index (DI). Results: In the hypothyroid group, basal glucose concentrations were mildly decreased (P = 0.0079), whereas basal insulin was increased (P = 0.019). Insulin sensitivity was reduced in the hypothyroid group (P<0.001), whereas AIRg was higher (P=0.01). Other parameters were not different between groups. Conclusions/Clinical Importance: Hypothyroidism negatively affects glucose homeostasis by inducing insulin resistance. In hypothyroid dogs, the disposition index (insulin sensitivity x insulin secretion) remained unchanged due to a compensatory increase in insulin secretion, thereby maintaining glucose tolerance. In cases with impaired insulin secretion, such as canine diabetes mellitus, concurrent hypothyroidism can have important clinical implications in the successful management of the disease. / Master of Science

Thesis (MPH.) -- University of Limpopo, 2014 / Objective: The purpose of this study was to determine the prevalence of impaired glucose tolerance, impaired fasting glucose, undiagnosed type 2 diabetes and its associated risk factors among adults patients attending the outpatient department of a level one hospital in a rural community of Barkley West, South Africa. Research methodology: This was a cross-sectional survey conducted by a simple random sampling of adults patients F 30 years old. Patients were screened using the American Diabetes Association and the World Health Organisation criteria. First, patients underwent the 75g oral glucose tolerance test and secondly, the 12-hours fasting plasma glucose tests after pre-test results of 5.5 mmol/L were obtained considered as positive for screening. To determine the prevalence of IGT, IFG, and undiagnosed type 2 diabetes; tests were conducted using both the capillary finger puncture and the laboratory methods. To ensure validity and reliability, each patient underwent two tests (fasting and random) by the capillary finger puncture method and two tests (fasting and random) by the laboratory method. Results: Eighty-five (85) questionnaires were distributed, supervised and returned by a research assistant, which brought the response rate to 100%. All patient known living with diabetes mellitus was not included in the study. The prevalence of IGT was 34.1% [34% for females and 9.4% for males] and that for IFG was 23.6% [25% for females and 6.0% for males]. The prevalence of undiagnosed type 2 diabetes discovered during the survey was 9.3% by 2-hours 75g glucose tolerance test [8.2% for females and 1.1% for males] and that by 12-hours fasting plasma glucose, the prevalence was 5.8% [4.7% for females and 1.1% for males].The associated risk factors were physical inactivity, overweight and obesity, unhealthy diet, alcohol consumption, hypertension, smoking habit, family history of diabetes, social deprivation and poverty. The prevalence of hyperglycaemia was also high among female patients due to a higher BMI with 25% overweight (females 18% overweight, males 7% overweight) and 75% obese (females 54% of obesity, males 21% of obesity); higher waist circumference with higher abdominal fat (females 71.7% had a W/C F 88 cm, males 28% had a W/C F 102 cm.); and a larger waist-to-hip ratio (females 61.1% had WHR > 0.85, males 7% had a WHR > 1.0). The sensitivity, specificity, positive and negative predictive values for IGT were 34%, 86%, 25%, and 86% and those for IFG were 24%, 86%, 19%, and 86% respectively. IGT sensitivity was greater than IFG sensitivity. xi Conclusion: There was a high prevalence of IGT, IFG and undiagnosed type 2 diabetes specifically among female patients. The ten percent difference of sensitivity between the two tests showed that the WHO diagnostic criteria produced more patients with the pathology than the ADA diagnostic criteria do. Patients attending the outpatient department of a level one hospital in Barkley West are at high risk of developing type 2 diabetes and remain unidentified, undetected, unscreened, undiagnosed and untreated. Obesity at primary health care level in the rural community of Barkley West needs to be addressed. . Keywords: Impaired glucose tolerance, prevalence, diabetes, screening, anthropometric measurements

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19892号 / 医博第4141号 / 新制||医||1016(附属図書館) / 32969 / 京都大学大学院医学研究科医学専攻 / (主査)教授 川村 孝, 教授 横出 正之, 教授 妹尾 浩 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

A inibição de mTOR com rapamicina exacerba a intolerância glicose associada a obesidade, um efeito que pode estar associado ao desenvolvimento de processo pró-inflamatório no tecido adiposo. O tratamento de camundongos com rapamicina exacerbou a intolerância a glicose e inflamação do tecido adiposo induzida por dieta hiperlipídica. In vitro, a inibição dos complexos 1 e 2 da mTOR com rapamicina e torina induziu polarização espontânea de macrófagos para o fenótipo M1 e aumentou a atividade fagocítica de macrófagos M0. Camundongos com ativação constitutiva de mTORC1 exclusivamente em células mielóides foram protegidos do ganho de peso, adiposidade, intolerância a glicose e a insulina induzidos pela ingestão de dieta hiperlipídica e apresentaram um aumento da polarização de macrófagos para o fenótipo M2. Em conjunto, nossos dados indicam que a atividade do complexo 1 da mTOR atenua o desenvolvimento da inflamação do tecido adiposo associada a obesidade por um mecanismo que envolve a polarização de macrófagos para o fenótipo M2. / Pharmacological mTOR inhibition with rapamycin exacerbates the glucose intolerance associated with obesity, such an effect that may be associated to the development of inflammatory process in adipose tissue. Rapamycin treatment exacerbates the glucose intolerance and adipose tissue inflammation induced by high fat diet feeding. In vitro, inhibition of mTOR complexes 1 and 2 with rapamycin and torin induced spontaneous macrophage polarization into a pro-inflammatory M1 phenotype and increased M0 macrophage phagocytosis. Mice with constitutive activation of mTOR complex 1 in myeloid cells were protected from body weight gain, fat accretion, glucose and insulin tolerance induced by the intake of high fat diet and displayed a significant increase in macrophage polarization to a M2 phenotype. Altogether, our findings indicate that the activity of mTOR complex 1 attenuates the development of adipose tissue inflammation induced by high fat feeding, through a mechanism that involves a higher polarization of macrophages to anti-inflammatory M2 phenotype.

Over the last few decades, ethanol production from renewable resources has been of interest as an alternative fuel to the current fossil fuel, due to the unstable oil market and in order to decrease net emission of carbon dioxide which leads to global warming. According to analyses of DG Transport and Energy (TREN), it is not possible to reach the current biofuels directive promoting 5,75 % biofuel by the year 2010, due to the markets and technologies, but by the year 2020 achievement of 6.9% is expected. This new law will increase biofuel demand by 3,1 %.Lignocelluloses materials, which are relatively cheap and plentiful, are considered to be the main source of feedstock’s for low-cost bio-ethanol production. The general procedure to convert lignocelluloses material to bioethanol is hydrolysis of the hemicelluloses and the cellulose to its monomer sugars, fermentation and distillation.Bacteria, yeasts and filamentous fungi are able to ferment hydrolysates from different plants and convert it to bioethanol.Mucor indicus is a filamentous fungus; it is able to utilize a wide range of hexoses, phentoses and disaccharides (cellobiose) in order to produce ethanol. The Ethanol yield and productivity of this microorganism from hexoses are as same as Saccharomyces cerevisiae. But the reason that it is one of the candidates for ethanol production is the fungus ability to utilize xylose. The cell wall of M.indicus contains significant quantity of chitosan/chitin which can be easily extracted. Chitosan is the deacetylated products of chitin. They have many applications in chemistry, biotechnology, medicine, veterinary, dentistry, agriculture, food processing, environmental protection, water purification, cosmetic and textile industries.The results of the current work show that the glucose concentration in the medium had a great impact on the lag phase, glucose consumption and ethanol production in both aerobic and anaerobic conditions. The lag phase increased as the initial concentration of glucose increased. While the glucose concentration increased above 190 g/l in the medium the glucose consumption and ethanol production decreased in both aerobic and anaerobic conditions. The glucose tolerance of M.indicus in both aerobic and anaerobic condition is about 190 g/l and in the anaerobic condition the ethanol tolerance of this fungus is around 70 g/. / Uppsatsnivå: D

Ad libitum high-fat diet (HFD)-induced obesity leads to insulin resistance in skeletal muscle, altered gene expression, and altered growth signaling, all of which contributes to pathological changes in metabolism. Liver kinase B1 (LKB1) is an important metabolism regulator. The purpose of this dissertation was to understand how knocking out LKB1 influences HFD induced adaptations in mouse skeletal muscle. To do so, control and skeletal muscle LKB1 knock-out (LKB1-KO) mice were put on either standard diet (STD) or HFD for 1 week or 14 weeks, or put on the HFD for 14 weeks and then switched to STD for 1 week (switched diet). The major differences in adaptation in the LKB1-KO mice include: 1) lower fasting blood glucose levels but impaired glucose tolerance compared to WT mice (although conflicting results are generated if the data is not normalized to fasting blood glucose levels), 2) altered expression of 16 HFD-induced genes, and 3) decreased muscle weight. The lower fasting blood glucose in LKB1-KO mice was likely due to elevated serum insulin levels, and the impaired glucose tolerance was associated with decreased phosphorylation of TBC1D1, an important regulator of insulin stimulated glucose uptake. 16 potential important target genes (metabolism, mitochondrial, cytoskeleton, cell cycle, cell-cell interactions, enzyme, ion channel) were identified in the context of HFD feeding and LKB1-KO. These genes were quantified by RT-PCR and grouped according to changes in their patterns of expression among the different groups. Among several other interesting changes in gene expression, the muscle growth-related protein, Ky was not affected by short-term HFD, but increased after long-term HFD, and did not decrease after switched diet, showing that its expression may be an important long-term adaptation to HFD. LKB1-KO promoted anabolic signaling through increasing t-eIF2α and eIF4E expression, and promoted protein degradation through increasing protein ubiquitination. Because the degradation is the main effect and lead to muscle weight decrease. The effect of HFD and/or LKB1-KO on the LKB1-AMPK system was also determined. The results showed that knocking-out LKB1 decreased AMPK activity, decreased nuclear distribution for AMPK α2 and increased AMPK α1 expression. Long-term HFD increased t-AMPK expression in LKB1-KO mice, decreased the cytoplasm p-AMPK and nuclear p/t-AMPK ratio in CON mice. Together the findings of this dissertation demonstrated HFD induced glucose/insulin tolerance, while LKB1-KO had a controversial effect on glucose/insulin sensitivity. Both HFD and LKB1-KO affect AMPK expression and cellular location, while LKB1-KO also affects AMPK activity. LKB1-KO promoted protein degradation through ubiquitination in skeletal muscle.

Background Surgery induces insulin resistance that might be alleviated by a nutritional drink given preoperatively. The authors hypothesized that some of the beneficial effects of the drink could be attributed to the volume component (approximately 1 L) rather than to the nutrients. Methods Sixty patients scheduled for elective total hip replacement under spinal anesthesia were recruited to a clinical trial, and randomly allocated to preoperative fasting, to oral ingestion of tap water, or to oral ingestion of a carbohydrate drink. An intravenous glucose tolerance test calculated glucose clearance and insulin sensitivity on the day before surgery, in the postoperative ward, and on the day after surgery. Other parameters were stress (cortisol in plasma and urine), muscle catabolism (urinary 3-methylhistidine), and wellbeing. Results Fifty-seven patients completed the study. In the postoperative ward, the glucose clearance and the insulin response had decreased from the previous day by 23% and 36%, respectively. Insulin sensitivity did not decrease until the next morning (−48%) and was due to an increased insulin response (+51%). Cortisol excretion was highest on the day of surgery, while 3-methylhistidine increased 1 day later. Follow-up on the third postoperative day showed an average of 1.5 complications per patient. Wellbeing was better 2 weeks after than before the surgery. None of the measured parameters differed significantly between the study groups. Conclusions Preoperative ingestion of tap water or a nutritional drink had no statistically significant effect on glucose clearance, insulin sensitivity, postoperative complications, or wellbeing in patients undergoing elective hip surgery. / <p>Funding Agencies|Olle Engkvist Byggmastare Foundation||Stockholm County Council|2009-0433|</p>

Während der Schwangerschaft vollziehen sich im Körper der Frau verschiedene Adaptionsmechanismen, um eine bestmögliche Versorgung für das heranwachsende Kind zu gewährleisten. Bei fortschreitender Gravidität entwickelt sich eine physiologische Insulinresistenz. Gelingt es den maternalen Betazellen des Pankreas‘ nicht, diese zu kompensieren, kann eine diabetische Stoffwechsellage bis hin zur Ausbildung eines Gestationsdiabetes (GDM) entstehen. Adipozytokine beeinflussen direkt lokale und periphere metabolische, endokrinologische sowie immunologische Prozesse. Inwieweit sie in der Gravidität eine Rolle spielen, ist bislang nicht hinreichend geklärt. In verschiedenen Studien wurde eine Beziehung zwischen den Fettgewebshormonen und der Glukosetoleranz in der Schwangerschaft nachgewiesen. Im Rahmen dieser Dissertation sollte eine Analyse zur Glukosetoleranz und zu Adipozytokinserumspiegeln bei Frauen unmittelbar nach der Entbindung vorgenommen werden. Ergebnisse oraler Glukosetoleranztests von gesunden Frauen 24 Stunden postpartal (n=65) wurden mit denen einer nicht-schwangeren, gesunden Kohorte (n=30) verglichen. Maternale und neonatale anthropometrische Daten wurden in Zusammenhang zu Adipozytokinen gestellt. Im Vergleich zu Frauen mit normaler Glukosetoleranz (NGT) postpartal konnten in dieser Studie signifikant verminderte Blutglukose – sowie nüchtern – Proinsulinspiegel in der nicht-schwangeren Kontrollgruppe nachgewiesen werden, wohingegen die nüchtern-C-Peptidspiegel erhöht waren. Weiterhin zeigten sich postpartal signifikant niedrigere Adiponektin-, aber höhere sOB-R- (soluble leptin receptor) sowie Leptinspiegel der NGT-Mütter im Vergleich zur Kontrollgruppe. Zusätzlich konnte eine Beziehung zwischen Adipozytokinserumspiegeln und Parametern der Glukosetoleranz bzw. Adipositas demonstriert werden. Daraus lässt sich die These ableiten, dass Frauen in der frühen Phase nach der Entbindung ähnliche biochemische Konstellationen wie beim metabolischen Syndrom, der gestörten Glukosetoleranz oder bei Störungen des Adipozytokinsystems aufweisen.