Glycogen storage and muscle glucose transporters (GLUT-4) of mice selectively bred for high voluntary wheel running

To examine the evolution of endurance-exercise behaviour, we have selectively bred four replicate lines of laboratory mice (Mus domesticus) for high voluntary wheel running ('high runner' or HR lines), while also maintaining four non-selected control (C) lines. By generation 16, HR mice ran ∼2.7-fold more than C mice, mainly by running faster (especially in females), a differential maintained through subsequent generations, suggesting an evolutionary limit of unknown origin. We hypothesized that HR mice would have higher glycogen levels before nightly running, show greater depletion of those depots during their more intense wheel running, and have increased glycogen synthase activity and GLUT-4 protein in skeletal muscle. We sampled females from generation 35 at three times (photophase 07:00 h-19:00 h) during days 5-6 of wheel access, as in the routine selection protocol: Group 1, day 5, 16:00 h-17:30 h, wheels blocked from 13:00 h; Group 2, day 6, 02:00 h-03:30 h (immediately after peak running); and Group 3, day 6, 07:00 h-08:30 h. An additional Group 4, sampled 16:00 h-17:30 h, never had wheels. HR individuals with the mini-muscle phenotype (50% reduced hindlimb muscle mass) were distinguished for statistical analyses comparing C, HR normal, and HR mini. HR mini ran more than HR normal, and at higher speeds, which might explain why they have been favored by the selective-breeding protocol. Plasma glucose was higher in Group 1 than in Group 4, indicating a training effect (phenotypic plasticity). Without wheels, no differences in gastrocnemius GLUT-4 were observed. After 5 days with wheels, all mice showed elevated GLUT-4, but HR normal and mini were 2.5-fold higher than C. At all times and irrespective of wheel access, HR mini showed approximately three-fold higher [glycogen] in gastrocnemius and altered glycogen synthase activity. HR mini also showed elevated glycogen in soleus when sampled during peak running. All mice showed some glycogen depletion during nightly wheel running, in muscles and/or liver, but the magnitude of this depletion was not large and hence does not seem to be limiting to the evolution of even-higher wheel running.

Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats

It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging. © 2013 Moura et al; licensee BioMed Central Ltd.

Glucose homoeostasis in rats exposed to acute intermittent hypoxia

Aim: Chronic exposure to intermittent hypoxia commonly induces the activation of sympathetic tonus and the disruption of glucose homoeostasis. However, the effects of exposure to acute intermittent hypoxia (AIH) on glucose homoeostasis are not yet fully elucidated. Herein, we evaluated parameters related to glucose metabolism in rats exposed to AIH. Methods: Male adult rats were submitted to 10 episodes of hypoxia (6% O2, for 45 s) interspersed with 5-min intervals of normoxia (21%), while the control (CTL) group was kept in normoxia. Results: Acute intermittent hypoxia rats presented higher fasting glycaemia, normal insulinaemia, increased lactataemia and similar serum lipid levels, compared to controls (n = 10, P < 0.05). Additionally, AIH rats exhibited increased glucose tolerance (GT) (n = 10, P < 0.05) and augmented insulin sensitivity (IS) (n = 10, P < 0.05). The p-Akt/Akt protein ratio was increased in the muscle, but not in the liver and adipose tissue of AIH rats (n = 6, P < 0.05). The elevated glycaemia in AIH rats was associated with a reduction in the hepatic glycogen content (n = 10, P < 0.05). Moreover, the AIH-induced increase in blood glucose concentration, as well as reduced hepatic glycogen content, was prevented by prior systemic administration of the β-adrenergic antagonist (P < 0.05). The effects of AIH on glycaemia and Akt phosphorylation were transient and not observed after 60 min. Conclusions: We suggest that AIH induces an increase in blood glucose concentration as a result of hepatic glycogenolysis recruitment through sympathetic activation. The augmentation of GT and IS might be attributed, at least in part, to increased β-adrenergic sympathetic stimulation and Akt protein activation in skeletal muscles, leading to a higher glucose availability and utilization. © 2013 Scandinavian Physiological Society.

Low-Level Fluoride Exposure Increases Insulin Sensitivity in Experimental Diabetes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of an acute β-adrenergic blockade on the blood glucose response during lactate minimum test

The aim of this study was to determine the relationship between blood lactate and glucose during an incremental test after exercise induced lactic acidosis, under normal and acute β-adrenergic blockade. Eight fit males (cyclists or triathletes) performed a protocol to determine the intensity corresponding to the individual equilibrium point between lactate entry and removal from the blood (incremental test after exercise induced lactic acidosis), determined from the blood lactate (Lacmin) and glucose (Glucmin) response. This protocol was performed twice in a double-blind randomized order by ingesting either propranolol (80 mg) or a placebo (dextrose), 120 min prior to the test. The blood lactate and glucose concentration obtained 7 minutes after anaerobic exercise (Wingate test) was significantly lower (p<0.01) with the acute β-adrenergic blockade (9.1±1.5 mM; 3.9±0.1 mM), respectively than in the placebo condition (12.4±1.8 mM; 5.0±0.1 mM). There was no difference (p>0.05) between the exercise intensity determined by Lacmin (212.1±17.4 W) and Glucmin (218.2±22.1 W) during exercise performed without acute β-adrenergic blockade. The exercise intensity at Lacmin was lowered (p<0.05) from 212.1±17.4 to 181.0±15.6 W and heart rate at Lacmin was reduced (p<0.01) from 161.2±8.4 to 129.3±6.2 beats min-1 as a result of the blockade. It was not possible to determine the exercise intensity corresponding to Glucmin with β-adrenergic blockade, since the blood glucose concentration presented a continuous decrease during the incremental test. We concluded that the similar pattern response of blood lactate and glucose during an incremental test after exercise induced lactic acidosis, is not present during β-adrenergic blockade suggesting that, at least in part, this behavior depends upon adrenergic stimulation.

Glucose-Insulin regulator for type 1 diabetes using high order neural networks

In this paper a Glucose-Insulin regulator for Type 1 Diabetes using artificial neural networks (ANN) is proposed. This is done using a discrete recurrent high order neural network in order to identify and control a nonlinear dynamical system which represents the pancreas? beta-cells behavior of a virtual patient. The ANN which reproduces and identifies the dynamical behavior system, is configured as series parallel and trained on line using the extended Kalman filter algorithm to achieve a quickly convergence identification in silico. The control objective is to regulate the glucose-insulin level under different glucose inputs and is based on a nonlinear neural block control law. A safety block is included between the control output signal and the virtual patient with type 1 diabetes mellitus. Simulations include a period of three days. Simulation results are compared during the overnight fasting period in Open-Loop (OL) versus Closed- Loop (CL). Tests in Semi-Closed-Loop (SCL) are made feedforward in order to give information to the control algorithm. We conclude the controller is able to drive the glucose to target in overnight periods and the feedforward is necessary to control the postprandial period.

Diabetes detection in Australian general practice: a comparison of diagnostic criteria

Objectives: To study the influence of different diagnostic criteria on the prevalence of diabetes mellitus and characteristics of those diagnosed. Design and setting: Retrospective analysis of data from the general-practice-based Australian Diabetes Screening Study (January 1994 to June 1995). Participants: 5911 people with no previous diagnosis of diabetes, two or more symptoms or risk factors for diabetes, a random venous plasma glucose (PG) level > 5.5 mmol/L and a subsequent oral glucose tolerance test (OGTT) result. Main outcome measure: Prevalence of undiagnosed diabetes based on each of three sets of criteria: 1997 criteria of the American Diabetes Association (ADA), 1996 two-step screening strategy of the Australian Diabetes Society (ADS) (modified according to ADA recommendations about lowered diagnostic fasting PG level), and 1999 definition of the World Health Organization (WHO). Results: Prevalence estimates for undiagnosed diabetes using the American (ADA), Australian (ADS) and WHO criteria (95% CI) were 9.4% (8.7%-10.1%), 16.0% (15.3%-16.7%) and 18.1% (17.1%-19.1%), respectively. People diagnosed with diabetes by fasting PG level (common to all sets of criteria) were more likely to be male and younger than those diagnosed only by 2 h glucose challenge PG level (Australian and WHO criteria only). The Australian (ADS) stepwise screening strategy detected 88% of those who met the WHO criteria for diabetes, including about three-quarters of those with isolated post-challenge hyperglycaemia. Conclusion: The WHO criteria (which include an OGTT result) are preferable to the American (ADA) criteria (which rely totally on fasting PG level), as the latter underestimated the prevalence of undiagnosed diabetes by almost a half. The Australian (ADS) strategy identified most of those diagnosed with diabetes by WHO criteria.

A diabetes: principais parâmetros para o controlo da diabetes

RESUMO: A Diabetes Mellitus é uma doença metabólica crónica, com deficiência a nível do metabolismo dos hidratos de carbono, lípidos e proteínas, resultante de deficiências na secreção ou ação da insulina, ou de ambas, que quando não tratada antecipadamente e de modo conveniente, pode ter consequências muito graves. Dado a incidência a nível mundial da Diabetes Mellitus, torna-se de elevada importância avaliar toda a sua envolvência e estudar bem quais os critérios a ter em consideração. Este trabalho propõe-se estudar para além dos parâmetros bioquímicos relacionados com a doença - Glicose e Hemoglobina Glicada A1c (HbA1c), analisar os resultados dos últimos cinco anos (2008-2012) dos ensaios interlaboratoriais do PNAEQ, do Departamento de Epidemiologia, do Instituto Nacional de Saúde Dr. Ricardo Jorge. Foram também analisadas as metodologias utilizadas e as variações interlaboratoriais, de forma a entender qual ou quais são os parâmetros mais adequados para o seu diagnóstico e controlo. Este estudo utilizou a população de laboratórios portugueses, públicos e privados, de Portugal Continental e Ilhas, um laboratório de Angola e outro de Macau que se inscreveram no PNAEQ nestes cinco anos, sendo a amostra composta pelo n.º de participações. No programa de Química Clinica foram distribuídas 38 amostras e no programa de HbA1c foram distribuídas 22 amostras. Para a glicose, o nível de desempenho nos ensaios é na globalidade das amostras de Excelente, no entanto verifica-se que sempre que a concentração da amostra é de nível patológico, que a maioria dos ensaios o desempenho foi inferior – Bom. O método de eleição e com CV% mais baixos foi o método da hexoquinase. Para a HbA1c, o nível de desempenho nos ensaios é na globalidade das amostras de Excelente. O método de eleição e com CV% mais baixos foi o método de HPLC. O CV% para a glicose ronda desde 2010 a 2012, os 3% e para a HbA1c foi de aproximadamente 4,0% em 2012. A HbA1c tem mostrado ser uma ferramenta muito útil, importante e robusta na monitorização da Diabetes, sendo hoje em dia quase sempre requisitada em análises de rotina a diabéticos de modo a prevenir complicações que possam vir a acorrer. No futuro poderá ser um importante, senão o parâmetro de futuro, para o diagnóstico da Diabetes, no entanto, mesmo já tendo sido muito trabalhada a sua padronização, ainda existem questões por responder como quais são na realidade todos os seus interferentes, qual a verdadeira relação da HbA1c com a glicose média estimada, em todas as populações e com estudos epidemiológicos. Também a própria educação do diabético e clínico deve ser aprimorada, pelo que neste momento as PTGO e os doseamentos de glicose em jejum devem ser utilizados e encontrando-se a Norma da DGS N.º 033/2011 de acordo com as necessidades e com o estado da arte deste parâmetro. A implementação da glicose média estimada será uma mais-valia na monitorização dos diabéticos pelo que deverá ser uma das prioridades a ter em conta no futuro desta padronização, uniformizando a decisão clinica baseada nela e minimizando a dificuldade de interpretação de resultados de laboratório para laboratório. --------------ABSTRACT: Diabetes Mellitus is a chronic metabolic disease, with a deficit in the metabolism of carbohydrates, lipids and proteins, resulting from deficiencies in insulin secretion or action, or both, which if, when not early treated in a proper way, may result in very serious consequences. Given the worldwide incidence of diabetes mellitus, it is highly important to evaluate all its background and study specifically all the criteria to take into consideration. The aim of this thesis is to study and evaluate beyond the biochemical parameters related to the disease - Glucose and Glycated Haemoglobin A1c (HbA1c), analyze the results of the last five years (2008-2012) of the PNAEQ interlaboratorial tests, in the Department of Epidemiology of National Institute of Health Dr. Ricardo Jorge. It is also intended to analyze the methodologies used and the interlaboratorial variations, in order to understand the most suitable parameters for the diagnosis and control. This study was based in a population of Portuguese laboratories, public and private, of Portugal mainland and islands, a laboratory of Angola and other from Macau, who enrolled in PNAEQ in these five years, and the sample was composed by the n. º of holdings. In the Clinical Chemistry Program there were distributed 38 samples and in the program HbA1c were distributed 22 samples. For glucose, the level of performance in the total nº of the samples was Excellent; however, it was found that when the concentration level of the sample was pathological, in most of the tests the performance was Good. The most preferred method with the lowest CV% is the hexokinase method. For the HbA1c, as a whole, the samples’ tests were Excellent, at the level of performance. The method of election with the lower CV% was the HPLC. The CV% for glucose was around 3%, from 2010 to 2012 and the HbA1c was approximately 4.0% in 2012. The HbA1c method has demonstrated to be a very useful tool, important and robust for monitoring diabetes, being nowadays, almost always required in routine analysis to prevent future complications. In the future it may be an important parameter, if not the most important, for the diagnosis of diabetes. However, despite it has already been standardized, there are still some questions that need to be answered, such as, which are in fact all their interferences, which is the true connection of HbA1c, when compared with the estimated average glucose, in all populations and epidemiological studies. Moreover, the education of the patient and the doctor concerning diabetes should be improved. Nowadays, the Oral Glucose Tolerance Test (OGTT) and fasting glucose determinations should be used and, the needs and the state of the art of this parameter, should be in accordance with the Standard DGS N. º 033/2011. The Implementation of the estimated average glucose will be an added value in monitoring diabetics and, therefore, should be a priority to consider in its future standardization and clinical decision based on it, will be uniform and the difficulty of interpreting results from laboratory to laboratory will be minimal.

Poots launches £18m state-of-the-art Telemonitoring NI service

Health Minister Edwin Poots today marked the roll-out of a ground-breaking hi-tech scheme which will enable more patients to monitor their health in their own homes. Following funding of £18m from the Department of Health, the newly named Centre for Connected Health and Social Care (CCHSC), part of the Public Health Agency, worked in partnership with business consortium TF3to establish the innovative Telemonitoring NI service. The service is now being delivered by the TF3 consortium in partnership with the Health and Social Care Trusts.Remote telemonitoring combines technology and services that enable patients with chronic diseases to test their vital signs such as pulse, blood pressure, body weight, temperature, blood glucose and oxygen levels at home on a daily basis. The service will now be rolled out to 3,500 patients across Northern Ireland per annum for a period of six years.Mr Poots today visited the home of Larne pensioner Michael Howard who has Chronic Pulmonary Obstructive Disorder (COPD) to hear how Telemonitoring NI has changed his life.During the visit Mr Poots said: "Chronic diseases such as heart disease, diabetes and COPD affect around three quarters of people over the age of 75. This is the generation from whom transport and mobility pose the biggest problems. The Telemonitoring NI service will allow thousands to monitor their vital signs without having to leave their own homes."It means that patients are able to understand and manage their condition better. Many say it has improved their confidence and given them peace of mind. With a health professional monitoring each patient's health on a daily basis, there is less need for hospital admission. Carers are also better informed with the pro-active support provided. It means earlier intervention in, and the prevention of, deterioration of condition, acute illness and hospital admissions."Telemonitoring NI is an excellent example of how the Health Service can innovateusing modern technology to deliver a better service for our patients."Eddie Ritson, Programme Director of CCHSC, PHA, said: "The roll-out of Telemonitoring NI represents a significant step towards providing quality care for the growing number of people with heart disease, stroke, some respiratory conditions and diabetes who want to live at home while having their conditions safely managed."This new service will give people more information which combined with timely advice will enable patients to gain more control over their health while supporting them to live independently in their own homes for longer."A patient will take their vital sign measurements at home, usually on a daily basis. and these will automatically be transmited to the Tf3 system. The resulting readings are monitored centrally by a healthcare professional working in the Tf3 triage team. If the patient's readings show signs of deterioration to an unacceptable level, they will be contacted by phone by a nurse working in a central team and if appropriate a healthcare professional in the patient's local Trust will be alerted to enable them to take appropriate action."Families and carers will also benefit from the reassurance that chronic health conditions are being closely monitored on an ongoing basis. The information collected through the service can also be used by doctors, nurses and patients in making decisions on how individual cases should be managed. "Using the service, Mr Howard, 71, who has emphysema - a long-term, progressive disease of the lungs that primarily causes shortness of breath - monitors his vital signs using the new technology every weekday morning. The information is monitored centrally and if readings show signs of deterioration to an unacceptable level, Mr Howard's local healthcare professional is alerted."Taking my readings is such a simple process but one that gives me huge benefits as it is an early warning system to me and also for the specialist nurses in charge of my care. Without the remote telemonitoring I would be running back and forward to the GPs' surgery all the time to have things checked out," he explained."Having my signs monitored by a nurse means any changes in my condition are dealt with immediately and this has prevented me from being admitted to hospital - in the past I've had to spend six days in hospital any time I'm admitted with a chest infection."The telemonitoring is not only reassuring for me, it also gives me more control over managing my own condition and as a result I have less upheaval in my life, and I'm less of a cost to the health care system. Most importantly, it gives me peace of mind and one less thing to worry about at my age."Patients seeking further information about the new telemonitoring service should contact their healthcare professional.

EXPOSICAO DE CIRURGIOES-DENTISTAS AO MERCURIO

The professional exposure of dental surgeons to mercury has attracted a great deal of attention from governmental organs and institutions in different countries. Considering that the normal ratio is 10 μg/1000 ml of urine, it was verified from tests that 72.7% of the professionals working in the dental practice in the city of Araraquara (SP) Brazil, show mercury levels above this limit. These results demonstrated the almost complete unawareness of many dentists to mercury and, consequently, precautionary measures were almost nonexistent.

Effects of the application of α1- and α2-adrenoceptor agonists and antagonists into the ventromedial hypothalamus on the sodium and potassium renal excretion

The effects of sodium and potassium excretion after intrahypothalamic administration of two α-adrenoceptor agonists and the effect of α-adrenoceptor antagonists were studied in groups of rats. Prazosin was equally effective at blocking the natriuretic and kaliuretic responses to the α1-adrenoceptor agonist phenylephrine and the mixed α1/α2-adrenoceptor agonist noradrenaline, while yohimbine which acts preferentially on α2-adrenoceptors was effective in potentiating these responses. These results suggest the presence of two types of α-adrenoceptors for the modulation of ventromedial hypothalamic pathways that interfere with the regulation of the two cations: stimulation of α1-adrenoceptors facilitates, while stimulation of α2-adrenoceptors inhibits the excretion of the ions.

Effects of antithyroid drug on the rectal temperature and metabolic parameters of ducks (Cairina moschata).

The effect of propylthiouracil oral treatment (400 mg/day per bird for 20 days) on body and thyroid weight, rectal temperature and plasma metabolic parameters of ducks (Cairina moschata) was determined. Propylthiouracil treatment produced a reduction (P less than .01) in body weight and an increase (P less than .01) in thyroid weight. The antithyroid drug also produced a decrease in rectal temperature starting from the 15th day of treatment, but did not significantly change blood glucose. Plasma free fatty acids and cholesterol concentrations progressively increased from the 5th and 10th day, respectively, in treated animals.