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The long terra effects of glucose on the rate of (pro) insulin biosynthesis and the amount of preproinsulin mRNA in rat islets maintained in tissue culture were investigated. The rate of (pro)insulin synthesis was 35 times greater in islets cultured for 6 days in 8 mM glucose than it was in islets cultured in 4 mM glucose. The preproinsulin mRNA content at this time was 2 fold greater in islets incubated with 8 mM glucose compared to 4 mM glucose. The rate of (pro)insulin synthesis and the preproinsulin mRNA content of islets cultured at 8 mM glucose were maximal since no further significant increases were observed in islets cultured at 16 mM glucose for 6 days. These results indicate that the long term effects of glucose on the rate of (pro)insulin synthesis in rat islets of Langerhans is mediated both by transcriptional and translational events and that translational events exert the major controlling influence.

No description available.

No description available.

Diabetes is a group of metabolic diseases characterized by hyperglycaemia resulting from defects in insulin secretion, insulin action, or both. Several models have been developed for describing the glucose-insulin system. Silber and Jauslin developed a semi-mechanistic integrated glucose insulin (IGI) model which simultaneously describe glucose and insulin profiles in either healthy subjects or type 2 diabetis mellitus (T2DM) patients. The model was developed for describing the basal system, i.e. when no drugs are present in the body. In this thesis the IGI model was extended to also include the effects of anti-diabetic drugs on glucose homeostasis. The model was extended to describe postprandial glucose and insulin excursions in T2DM patients treated with either biphasic insulin aspart or the GLP-1 receptor agonist liraglutide. These extensions make the model a useful tool in drug development as it can be used for elucidating the effects of new products as well as for clinical trial simulation. In this thesis several modelling tasks were also performed to get a more mechanistic description of the glucose-insulin system. A model was developed which describes the release of the incretin hormones glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 following the ingestion of various glucose doses. The effects of these hormones on the beta cell function were incorporated in a model describing both the C-peptide and insulin concentrations in healthy subjects and T2DM patients during either an oral glucose tolerance test or an isoglycaemic intravenous glucose infusion. By including measurements of both C-peptide and insulin concentrations in the model it could also be used to characterize the hepatic extraction of insulin.

Diabetes and insulin resistance are on the rise in the United States. Early detection and deployment of therapies has allowed for the reversal of pancreatic beta cell damage. Unfortunately, not all providers can offer the support to facilitating the required life style modifications. The introduction of clinical health consultants (CHC) as supplemental care has improved patient health for a variety of chronic diseases. Missing in the literature are studies investigating the correlation between the number of CHC interactions and improvement in biomarkers. The study utilized a non-experimental, retrospective study design to evaluate the relationship between the use between the use of CHCs and the number of CHC interactions, and the mean changes in glucose, hemoglobin A1c, insulin, proinsulin, C-peptide, and 1,5-anhydroglucitol, over a one-year period for patients presented with the opportunity to participate in CHC interactions. The subjects’ follow-up results were compared to their initial results for each group using the ANCOVA and one-way t-test. A statistically significant difference was detected between the mean change in BMI and the use of CHCs (p

Made available in DSpace on 2014-06-11T19:22:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-12-02Bitstream added on 2014-06-13T19:08:20Z : No. of bitstreams: 1 gomes_prl_me_prud.pdf: 496954 bytes, checksum: 1a8cc366f4f6c4e8b007f0dafc207ad0 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação para o Desenvolvimento da UNESP (FUNDUNESP) / A gravidez é um período de ajustes metabólicos e, quando associado ao tabagismo provoca alterações que trazem malefícios tanto à saúde materna quanto à saúde fetal. Assim, o estudo investigou o efeito da exposição à fumaça de cigarro sobre a expressão do transportador de glicose GLUT4 e parâmetros séricos e morfométricos de ratas prenhes e sua prole. Foram utilizadas ratas Wistar divididas em: CG- controle sacrificadas após a gestação, com prole adotada pelo grupo CL; CL - controle sacrificadas após o término da lactação; FG – expostas à fumaça de cigarro até o período gestacional e sacrificadas posteriormente, com prole adotada pelo grupo FL; FG – expostas à fumaça de cigarro até o fim da amamentação e posteriormente sacrificadas. As proles foram divididas por sexo e de acordo com a exposição ou não da rata à fumaça. Foram coletados sangue e tecidos para análise de glicemia e do conteúdo gênico e protéico de GLUT4. Nas ratas expostas à fumaça de cigarro, houve redução de peso corpóreo e de tecido adiposo, aumento da glicemia e modulação do transportador GLUT4 no músculo esquelético. Nas proles, houve... / Pregnancy is a period of metabolic adjustments, and when associated with cigarette smoke causes changes both to maternal health as the fetal. The study has investigated the effect of cigarette smoke exposure on the expression of glucose transporter GLUT4 and morphometric parameters and serum of pregnant smoker rats and their offspring. Wistar rats were divided in: CG- nonsmokers sacrificed after pregnancy with offspring adopted by CL; CL – nonsmoker group sacrificed after the end of lactation; FG – smoker group sacrificed after pregnancy with offspring adopted by FL; FL – smoker sacrificed after the end of lactation. The offspring was divided by sex and according to the protocol of their mothers. Blood and tissue were collected for analysis of glucose and the content of GLUT4 gene and protein. In smoker mothers, body weight and adipose tissue were reduced, glucose level was increased, and GLUT4 expression was higher in skeletal muscle. In offspring... (Complete abstract click electronic access below)

A thesis submitted to the School of Graduate Studies in partial fulfillment of the requirements for the degree Master of Science. / Sprint interval training (SIT) is a time-efficient strategy to improve cardiorespiratory fitness; however, most protocols have been studied in a laboratory setting and require specialized equipment. We investigated the efficacy of brief intense stair climbing as a practical model of SIT to improve cardiometabolic health, with a key measure being cardiorespiratory fitness as indicated by peak oxygen uptake (VO2peak). Two separate studies, each consisting of an acute and chronic phase, were conducted in a total of 31 sedentary women (age=24±10 y; BMI=23±4 kg•m-2). The acute phase of Study 1 established that the heart rate (HR), blood lactate concentration (BLa), and rating of perceived exertion (RPE) responses were similar when participants (n=8) performed a SIT protocol that involved 3x20-s “all-out” efforts of either continuous stair climbing or cycling, interspersed with 2 min of recovery. The chronic phase demonstrated that when participants (n=12) performed the 3x20-s stair climbing protocol 3 d•wk-1 for 6 wk, absolute and relative VO2peak increased by 12%, or ~1 metabolic equivalent (1.80±0.25 to 2.02±0.27 L•min-1, p<0.001), as there were no changes in body mass (p=0.35), fat free mass (FFM; p=0.09) or % body fat (p=0.42). There were also no changes in resting systolic and diastolic blood pressure (BP; p=0.82 and p=0.97, respectively), resting HR (p=0.62), and fasting insulin sensitivity (p=0.52). The acute phase of Study 2 established that the HR and RPE responses were similar when participants (n=11) performed three different stair climbing protocols. The protocols investigated include the 3x20-s continuous ascent model used in Study 1 (protocol 1), as well as 3x60-s bouts of ascending and descending either one or two flights of stairs, with 60-s of recovery (protocol 2 and 3, respectively). The chronic phase demonstrated that when the same group of subjects performed the 3x60-s 1-flight protocol 3 d•wk-1 for 6 wk, absolute and relative VO2peak increased by 8 and 7%, respectively (1.79±0.36 to 1.93±0.39 L•min-1, p=0.001; 31.2±4.6 to 33.3±5.3 mL•kg-1•min-1; p=0.01). Despite no changes in % body fat (p=0.10), there was an increase 3% increase in FFM (p<0.001). There was no change in systolic (p=0.50) and diastolic BP (p=1.00), but resting HR improved by 8% after training (p=0.03). The change in insulin sensitivity derived from an OGTT was 7.1±11 mg I2•mmol-1•mIU-1•min-1 (p=0.056). These findings demonstrate that brief intense stair climbing is a practical, time-efficient strategy to improve cardiorespiratory fitness in previously untrained women. / Thesis / Master of Science (MSc) / Sprint interval training (SIT), involving brief bouts of very intense exercise separated by short periods of recovery, is a time-efficient alternative to traditional endurance training for improving fitness. This has largely been established in laboratory settings using specialized equipment, which is impractical for many individuals. This project examined whether brief intense stair climbing was a practical model of SIT to elicit adaptations previously shown with cycling protocols. Subjects performed either three 20-s ascents interspersed with 2 min recovery periods, or three 60-s bouts of ascending and descending one or two flights of stairs, with 60-s recovery periods. Both protocols were 10 min in duration including warm-up and cool-down, and subjects trained three days per week for six weeks. The main finding was that stair climbing is a practical, time-efficient model to improve fitness in previously sedentary individuals.

yes / Wnt signalling and its downstream effectors are well known for their roles in embryogenesis and tumourigenesis, including the regulation of cell proliferation, survival and differentiation. In the nervous system, Wnt signalling has been described mainly during embryonic development, although accumulating evidence suggests that it also plays a major role in adult brain morphogenesis and function. Studies have predominantly concentrated on memory formation in the hippocampus, although recent data indicate that Wnt signalling is also critical for neuroendocrine control of the developed hypothalamus, a brain centre that is key in energy balance regulation and whose dysfunction is implicated in metabolic disorders such as type 2 diabetes and obesity. Based on scattered findings that report the presence of Wnt molecules in the tanycytes and ependymal cells lining the third ventricle and arcuate nucleus neurones of the hypothalamus, their potential importance in key regions of food intake and body weight regulation has been investigated in recent studies. The present review brings together current knowledge on Wnt signalling in the hypothalamus of adult animals and discusses the evidence suggesting a key role for members of the Wnt signalling family in glucose and energy balance regulation in the hypothalamus in diet-induced and genetically obese (leptin deficient) mice. Aspects of Wnt signalling in seasonal (photoperiod sensitive) rodents are also highlighted, given the recent evidence indicating that the Wnt pathway in the hypothalamus is not only regulated by diet and leptin, but also by photoperiod in seasonal animals, which is connected to natural adaptive changes in food intake and body weight. Thus, Wnt signalling appears to be critical as a modulator for normal functioning of the physiological state in the healthy adult brain, and is also crucial for normal glucose and energy homeostasis where its dysregulation can lead to a range of metabolic disorders.

yes / Metabolic syndrome is a global public health problem and predisposes individuals to obesity, diabetes and cardiovascular disease. Although the underlying mechanisms remain to be elucidated, accumulating evidence has uncovered a critical role of adipokines. Chemerin, encoded by the gene Rarres2, is a newly discovered adipokine involved in inflammation, adipogenesis, angiogenesis and energy metabolism. In humans, local and circulating levels of chemerin are positively correlated with body mass index and obesity-related biomarkers. In this review, we discuss both peripheral and central roles of chemerin in regulating body metabolism. In general, chemerin is upregulated in obese and diabetic animals. Previous studies by gain or loss of function show an association of chemerin with adipogenesis, glucose homeostasis, food intake and body weight. In the brain, the hypothalamus integrates peripheral afferent signals including adipokines to regulate appetite and energy homeostasis. Chemerin increases food intake in seasonal animals by acting on hypothalamic stem cells, the tanycytes. In peripheral tissues, chemerin increases cell expansion, inflammation and angiogenesis in adipose tissue, collectively resulting in adiposity. While chemerin signalling enhances insulin secretion from pancreatic islets, contradictory results have been reported on how chemerin links to obesity and insulin resistance. Given the association of chemerin with obesity comorbidities in humans, advances in translational research targeting chemerin are expected to mitigate metabolic disorders. Together, the exciting findings gathered in the last decade clearly indicate a crucial multifaceted role for chemerin in the regulation of energy balance, making it a promising candidate for urgently needed pharmacological treatment strategies for obesity.