Gluconeogenesis and glucose replacement rate during long-term fasting of Japanese quails

Gluconeogenic activity and kinetic parameters of glucose metabolism were estimated during the different phases of prolonged food deprivation in quails. Gluconeogenic activity, estimated from the rate of increase of incorporation of (HCO3-)-C-14 into circulating glucose, was significantly higher in fasted quails than in fed birds, whatever the period of food deprivation. However, gluconeogenic activity during phase II, although higher than in the fed state, was significantly lower than in quails fasted for 2 days (phase I) or in those on the final (phase III) period of starvation. Gluconeogenic activity did not differ significantly in birds from phases I and III. Rates of glucose replacement, estimated with [6-H-3]-glucose, were very high (20.5 mg . kg(-1). min(-1)) in fed quails and were markedly reduced (to about 42% of fed values) by fasting, no difference being observed between quails fasted for 2 and 5 days. Because of the poor condition of the birds, glucose replacement rates could not be measured during phase III. The present data are the first to provide direct evidence for the changes in gluconeogenesis which occur during prolonged food deprivation.

Glucose metabolism in the erythrocytes of the buffalo (Bubalus bubalis)

(CO2)-C-14 production from [1-C-14] glucose, the rate of glycolysis measured by the value of lactate production and the activities of various enzymes were determined in buffalo erythrocytes. Buffalo red cell glycolytic metabolites were estimated and used for the calculation of the mass action ratios of reactions catalyzed by the glycolytic enzymes of Bubalus bubalis. A comparison of the values of the mass action ratios with the equilibrium constants of the various glycolytic reactions indicate that hexokinase, phosphofructokinase, phosphoglycerate kinase and pyruvate kinase reactions are displaced from equilibrium, suggesting a regulatory role for each of these enzymes in buffalo erythrocyte glycolysis. (C) 1997 Elsevier B.V.

Protein malnutrition does not impair glucose metabolism adaptations to exercise-training

Malnutrition is a common health problem in developing countries and is associated with alterations in glucose metabolism. In the present study we examine the effects of chronic aerobic exercise on some aspects of glucose metabolism in protein-deficient rats. Two groups of adult rats (90 days old) were used: Normal protein group (17%P)- kept on a normal protein diet during intra-uterine and postnatal life and Low protein group (6%P)- kept on a low protein diet during intrauterine and post natal life. After weaning (21 days old), half of the 17%P and 6%P rats were assigned to a Sedentary (Sed) or an Exercise-trained (Exerc = swimming, 1 hr/day, 5 days/week, supporting an overload of 5% of body weight) subgroup. The area under blood glucose concentration curve (Delta G) after an oral glucose load was higher in 17%P Sed rats (20%) than in other rats and lower in 6%P Exerc (11%) in relation to 6% Sed rats. The post-glucose increase in blood insulin (Delta I) was also higher in 17%P Sed (9%) than in other rats. on the other hand, the glucose disappearance rate after exogenous subcutaneous insulin administration (Kitt) was lower in 17%P Sed rats (66%) than in other rats. Glucose uptake by soleus muscle was higher in Exerc rats (30%) than in Sed rats. Soleus muscle glycogen synthesis was reduced in 6%P Sed rats (41%) compared to 17%P Sed rats but was restored in 6%P Exerc rats. Glycogen concentration was elevated in Exerc (32%) rats in comparison to Sed rats. The present results indicate that glucose-induced insulin release is reduced in rats fed low protein diet. This defect is counteracted by an increase in the sensitivity of the target tissues to insulin and glucose homeostasis is maintained. This adaptation allows protein deficient rats to preserve the ability to appropriately adapt to aerobic physical exercise training. (C) 2000 Elsevier B.V.

Protein deficiency during pregnancy and lactation impairs glucose-induced insulin secretion but increases the sensitivity to insulin in weaned rats

We studied glucose homeostasis in rat pups from darns fed on a normal-protein (170 g/kg) (NP) diet or a diet containing 60 g protein/kg (LP) during fetal life and the suckling period. At birth, total serum protein, serum albumin and serum insulin levels were similar in both groups. However, body weight and serum glucose levels in LP rats were lower than those in NP rats. At the end of the suckling period (28 d of age), total serum protein, serum albumin and serum insulin were significantly lower and the liver glycogen and serum free fatty acid levels were significantly higher in LP rats compared with NP rats. Although the fasting serum glucose level was similar in both groups, the area under the blood glucose concentration curve after a glucose load was higher for NP rats (859 (SEM 58) mmol/l per 120 min for NP rats v. 607 (SEM 52) mmol/l per 120 min for LP rats; P < 0.005). The mean post-glucose increase in insulin was higher for NP rats (30 (SEM 4.7) nmol/l per 120 min for NP rats v. 17 (SEM 3.9) nnol/l per 120 min for LP rats; P < 0.05). The glucose disappearance rate for NP rats(0.7 (SEM 0.1) %/min) was lower than that for LP rats (1.6 (SEM 0.2) %/min; P < 0.001). Insulin secretion from isolated islets (1 h incubation) in response to 16.7 mmol glucose/l was augmented 14-fold in NP rats but only 2.6-fold in LP rats compared with the respective basal secretion (2.8 mmol/l; P <0.001). These results indicate that in vivo as well as in vitro insulin secretion in pups from dams maintained on a LP diet is reduced. This defect may be counteracted by an increase in the sensitivity of target tissues to insulin.

Protein Deficiency Attenuates the Effects of Alloxan on Insulin Secretion and Glucose Homeostasis in Rats

We have investigated the effect of alloxan on insulin secretion and glucose homeostasis in rats maintained on a 17% protein (normal protein, NP) or 6% protein (low protein, LP) diet from weaning (21 days old) to adulthood (90 days old). The incidence of alloxan diabetes was higher in the NP (3.5 times) than in the LP group. During an oral glucose tolerance test, the area under serum glucose curve was lower in LP (57%) than in NP rats while there were no differences between the two groups in the area under serum insulin curve. The serum glucose disappearance rate (Kitt) after exogenous insulin administration was higher in LP (50%) than in NP rats. In pancreatic islets isolated from rats not injected with alloxan, acute exposure to alloxan (0.05 mmol/L) reduced the glucose- or arginine-stimulated insulin secretion of NP islets by 78% and 56%, respectively, whereas for islets from LP rats, the reduction was 47% and 17% in the presence of glucose and arginine, respectively. Alloxan treatment reduced the glucose oxidation in islets from LP rats to a lesser extent than in NP islets (23% vs. 56%). In conclusion, alloxan was less effective in producing hyperglycemia in rats fed a low protein diet than in normal diet rats. This effect is attributable to an increased peripheral sensivity to insulin in addition to a better preservation of glucose oxidation and insulin secretion in islets from rats fed a low protein diet.

Glucose homeostasis in pregnant rats submitted to dietary protein restriction

In the present work, we examined the effects of feeding a low protein diet during pregnancy on glucose-induced insulin secretion and glucose homeostasis in rats. Young (60 days), pregnant (P) or non-pregnant (NP) rats were fed during pregnancy or for 21 days (the NP) a normal (17%) or a low (6%) protein diet. Serum glucose and insulin levels and pancreas insulin content in the fed state; total area under serum glucose curve (AG) after a glucose load and serum glucose disappearance rate (Kitt) after insulin administration; as well as 86Rb outflow, 45Ca uptake and insulin secretion by isolated pancreatic islets in response to glucose were evaluated. Serum glucose was lower in 17%-P (12%) and 6%-P (27%) than in corresponding NP-rats. Serum insulin was higher in 17%- P (153%) and 6%-P (77%) compared to the corresponding NP-rats. Pancreatic insulin was higher in 6%-rats (55%) than in 17%-rats. No differences were found in AG among the groups whereas Kitt was lower in 6%-NP and higher in 6%-P than in the equivalent 17% rats. Increasing glucose concentration from 2.8 to 16.7 mmol/l, reduced 86Rb outflow from isolated islets from all groups. Increasing glucose concentration from 2.8 to 16.7 mmol/l elevated 45Ca uptake by 17%-NP (47%), 17%-P (40%) and 6%-P (214%) islets but not by 6%-NP ones. The increase in 45Ca uptake was followed by an increase in insulin release by the 17%-NP (2767%), 17%-P (2850%) and 6%-P (1200%) islets. In conclusion, 6%-P rats show impaired glucose induced insulin secretion related to reduced calcium uptake by pancreatic islets. However, the poor insulin secretion did not fully compensate the high peripheral sensitivity to the hormone, resulting in hypoglycemia.

Resting heart rate: Its correlations and potential for screening metabolic dysfunctions in adolescents

Background: In pediatric populations, the use of resting heart rate as a health index remains unclear, mainly in epidemiological settings. The aims of this study were to analyze the impact of resting heart rate on screening dyslipidemia and high blood glucose and also to identify its significance in pediatric populations.Methods: The sample was composed of 971 randomly selected adolescents aged 11 to 17 years (410 boys and 561 girls). Resting heart rate was measured with oscillometric devices using two types of cuffs according to the arm circumference. Biochemical parameters triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and glucose were measured. Body fatness, sleep, smoking, alcohol consumption and cardiorespiratory fitness were analyzed.Results: Resting heart rate was positively related to higher sleep quality (β = 0.005, p = 0.039) and negatively related to cardiorespiratory fitness (β = -0.207, p = 0.001). The receiver operating characteristic curve indicated significant potential for resting heart rate in the screening of adolescents at increased values of fasting glucose (area under curve = 0.611 ± 0.039 [0.534 - 0.688]) and triglycerides (area under curve = 0.618 ± 0.044 [0.531 - 0.705]).Conclusion: High resting heart rate constitutes a significant and independent risk related to dyslipidemia and high blood glucose in pediatric populations. Sleep and cardiorespiratory fitness are two important determinants of the resting heart rate. © 2013 Fernandes et al.; licensee BioMed Central Ltd.

Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients

To identify early metabolic abnormalities in type 2 diabetes mellitus, we measured insulin secretion, sensitivity to insulin, and hepatic insulin extraction in 48 healthy normal glucose-tolerant Brazilians, first-degree relatives of type 2 diabetic patients (FH+). Each individual was matched for sex, age, weight, and body fat distribution with a person without history of type 2 diabetes (FH-). Both groups were submitted to a hyperglycemic clamp procedure (180 mg/dl). Insulin release was evaluated in its two phases. The first was calculated as the sum of plasma insulin at 2.5, 5.0, 7.5, and 10.0 min after the beginning of glucose infusion, and the second as the mean plasma insulin level in the third hour of the clamp procedure. Insulin sensitivity index (ISI) was the mean glucose infusion rate in the third hour of the clamp experiment divided by the mean plasma insulin concentration during the same period of time. Hepatic insulin extraction was determined under fasting conditions and in the third hour of the clamp procedure as the ratio between C-peptide and plasma insulin levels. FH+ individuals did not differ from FH- individuals in terms of the following parameters [median (range)]: a) first-phase insulin secretion, 174 (116-221) vs 207 (108-277) µU/ml, b) second-phase insulin secretion, 64 (41-86) vs 53 (37-83) µU/ml, and c) ISI, 14.8 (9.0-20.8) vs 16.8 (9.0-27.0) mg kg-1 min-1/µU ml-1. Hepatic insulin extraction in FH+ subjects was similar to that of FH- ones at basal conditions (median, 0.27 vs 0.27 ng/µU) and during glucose infusion (0.15 vs 0.15 ng/µU). Normal glucose-tolerant Brazilian FH+ individuals well-matched with FH- ones did not show defects of insulin secretion, insulin sensitivity, or hepatic insulin extraction as tested by hyperglycemic clamp procedures.

Endurance training improves responsiveness to insulin and modulates insulin signal transduction through the phosphatidylinositol 3-kinase/Akt-1 pathway

Background: Endurance training increases insulin-stimulated muscle glucose transport and leads to improved metabolic control in diabetic patients.Objective: To analyze the effects of endurance training on the early steps of insulin action in muscle of rats. Design: Male rats submitted to daily swimming for 6 weeks were compared with sedentary controls. At the end of the training period, anesthetized animals received an intravenous (i.v.) injection of insulin and had a fragment of their gastrocnemius muscle excised for the experiments.Methods: Associations between insulin receptor, insulin receptor substrates (IRS)-1 and -2 and phosphatidylinositol 3-kinase (PI3-kinase) were analyzed by immunoprecipitation and immunoblotting. Akt-1 serine phosphorylation and specific protein quantification were detected by immunoblotting of total extracts, and IRS-1/IRS-2-associated PI3-kinase activity were determined by thin-layer chromatography.Results: Insulin-induced phosphorylation of IRS-1 and IRS-2 increased respectively by 1.8-fold (P < 0.05) and 1.5-fold (P < 0.05), whereas their association with PI3-kinase increased by 2.3-fold (P < 0.05) and 1.9-fold (P < 0.05) in trained rats as compared with sedentary controls, respectively. The activity of PI3-kinase associated with IRS-1 and IRS-2 increased by 1.8-fold (P < 0.05) and 1.7-fold (P < 0.05) respectively, in trained rats as compared with their untrained counterparts. Serine phosphorylation of Akt-1/PKB increased 1.7-fold (P < 0.05) in trained rats in response to insulin. These findings were accompanied by increased responsiveness to insulin as demonstrated by a reduced area under the curve for insulin during an i.v. glucose tolerance test, by increased glucose disappearance rate during an insulin tolerance test, and by increased expression of glucose transporter-4.Conclusions: the increased responsiveness to insulin induced by chronic exercise in rat skeletal muscle may result, at least in part, from the modulation of the insulin signaling pathway at different molecular levels.

Capacidade aeróbia de ratos alimentados com dieta rica em frutose

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

Acute exercise reverses aged-induced impairments in insulin signaling in rodent skeletal muscle

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

Metabolismo glicídico em ratos submetidos a desnervação do músculo esquelético e ao exercício de natação

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

Reposição de cães em área endêmica para leishmaniose visceral

Esse trabalho objetivou estimar a reposição de cães em área endêmica para leishmaniose visceral, onde a eutanásia de animais soropositivos é indicada como medida de controle, e avaliar os motivos que levaram a aquisição ou não de novos animais. Houve a reposição em 44,5% dos casos, principalmente devido à necessidade de companhia ou guarda. O principal motivo para a não-reposição foi o temor da leishmaniose visceral.

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.

Moderate physical activity from childhood contributes to metabolic health and reduces hepatic fat accumulation in adult rats

Background: Obesity, oxidative stress and inflammation, by triggering insulin resistance, may contribute to the accumulation of hepatic fat, and this accumulation by lipotoxicity can lead the organ to fail. Because obesity is growing at an alarming rate and, worryingly, in a precocious way, the present study aimed to investigate the effects of moderate physical training performed from childhood to adulthood on liver fat metabolism in rats. Methods. Twenty rats that were 28days old were divided into two groups: control (C) and trained (T). The C Group was kept in cages without exercise, and the T group was submitted to swimming exercise for 1hour/day, 5days/week from 28 to 90days of age (8weeks) at 80% of the anaerobic threshold determined by the lactate minimum test. At the end of the experiment, the body weight gain, insulin sensitivity (glucose disappearance rate during the insulin tolerance test), concentrations of free fatty acids (FFA) and triglycerides (TG) and hepatic lipogenic rate were analyzed. For the statistical analysis, the Student t-test was used with the level of significance preset at 5%. Results: The T group showed lower body weight gain, FFA concentrations, fat accumulation, hepatic lipogenic rate and insulin resistance. Conclusion: The regular practice of moderate physical exercise from childhood can contribute to the reduction of obesity and insulin resistance and help prevent the development of accumulation of hepatic fat in adulthood. © 2013de Moura et al; licensee BioMed Central Ltd.