Long-term calorie restriction prevented memory impairment in middle-aged male mice and increased a marker of DNA oxidative stress in hippocampal dentate gyrus.

Calorie restriction (CR) is a non-invasive and economic approachknown to increase healthspan and life expectancy, through a decrease in oxidative stress, an increase in neurotrophins, among other benefits. However, it is not clear whether its benefit could be noted earlier, as at the beginning of middle-age. Hence, weaimed to determine whether six months of long-term CR, from early adulthood to the beginning of middle age (10 months of age) could positively affect cognitive, neurochemical, and behavioral parameters. Male C57BL6/J mice were randomly distributed into Young Control (YC, ad libitum food), Old Control (OC, ad libitum food), and Old Restricted (OR, 30 % of caloric restriction) groups. To analyze the cognitive and behavioral aspects, the novel object recognition task (NOR), open field, and elevated plus maze tests were performed. In addition, immunohistochemistry targetingΔFosB (neuronal activity), brain-derived neurotrophic factor (BDNF) and the DNA oxidative damage (8OHdG) in hippocampal subfields CA1, CA2, CA3, and dentate gyrus (DG), and in basolateral amygdala and striatum were performed. Our results showed that long-term CR prevented short-term memory impairment related to aging and increased 8OHdG in hippocampal DG. BDNF was not involved in the effects of either age or CR on memory at middle-age, as it increased in CA3 of the OC group but was not altered in OR. Regarding anxiety-type behavior, no parameter showed differences between the groups. In conclusion, while the effects of long-term CR on anxiety-type behavior were inconclusive, it mitigated the memory deficit related to aging, which was accompanied by an increase in hippocampal 8OHdG in DG. Future studies should investigate whether the benefits of CR would remain if the restriction were interrupted after this long-term protocol.

Photobiomodulation in diabetic rats: Effects on morphological, pancreatic parameters, and glucose homeostasis.

Photobiomodulation (PBM) has therapeutic effects on wound healing, diabetic microangiopathy, and retinopathy. However, little is known about the use of PBM for the treatment of diabetes mellitus (DM). In this context, we aimed to evaluate the effects of PBM on pancreas morphology and insulin and glucose tolerance in an experimental model of DM. Thus, DM was induced by streptozotocin (STZ) (60 mg/kg). Subsequently, the rats were treated with PBM (808 nm and 30 J/cm2 ). After euthanasia, morphometric parameters and immunoreactivity for insulin and 8-OHdG were evaluated in the pancreas. The results showed that treated animals had higher values of body mass and higher values in the number of beta cells in the pancreas. In conclusion, PBM resulted in decreased weight loss in STZ-induced diabetic rats and presented a stimulatory effect on the pancreas of the treated animals, highlighting the promising effects of this therapy in the clinical condition of DM.

Effect of the ACTN-3 gene polymorphism on functional fitness and executive function of elderly.

During aging, physical integrity and cognitive abilities, especially executive function, become compromised, directly influencing the quality of life of the elderly. One good strategy to ensure healthy aging is the practice of physical exercise. Activities to improve aerobic capacity and muscle strength are extremely important in old age. However, some genetic factors can interfere both positively and negatively with these gains. In this context, the polymorphism rs1815739 (R577X) of the α-actinin 3 gene (ACTN-3) is commonly studied and related to muscle phenotype. Thus, the present study aimed to investigate the effect of the ACTN-3 gene polymorphism on the functional fitness (measured by the Senior Fit test) and cognitive capacity (evaluated by the Stroop test) of the elderly (n = 347), both men and women. We did not find the effect of genotype on functional fitness, but we did observed a positive effect of the ACTN-3 gene polymorphism on executive function. The presence of the X allele of the ACTN3 gene in the elderly was related to a better performance in the Stroop test (shorter answer time). Our results showed that ACTN-3 gene polymorphism affects the executive function of the elderly but not their functional fitness.

Effects of photobiomodulation on glucose homeostasis and morphometric parameters in pancreatic islets of diabetic mice.

High-fat diets lead to accumulation of body fat that is associated with the onset of insulin resistance and type II diabetes mellitus. On the other hand, photobiomodulation (PBM) is an electrophysical resource that interacts with cells, stimulating mitochondrial respiration, increasing ATP production, reducing key inflammatory mediators, inhibiting apoptosis, and stimulating angiogenesis. However, little is known about its therapeutic effectiveness on the development of diabetes in diet-induced obese mice. Thus, our aim was to evaluate the effect of PBM applied single point over the pancreas area on glucose homeostasis, insulin expression, and pancreatic morphometric parameters of mice submitted to high-fat diet for 12 weeks. Male mice C57BL6/J were divided into three groups: control group (C), diabetic group (D), and diabetic + PBM (D + PBM). The treatment with PBM started at 9th week and ended in the 12th week, applied 3 × /week. Body mass, fast blood glucose, and glucose and insulin tolerance were evaluated. Immunohistochemistry to detect insulin expression and pancreatic morphometry were also performed. At the end of 12th week, both groups submitted to high-fat diet showed an increase in body mass, adiposity, disturbances on glucose homeostasis, and high insulin expression when compared to the control group. However, mice treated with PBM had more discrete impairments on glucose homeostasis during the glucose tolerance test when compared to untreated D animals. Despite modest, the results were positive and encourage future investigations to explore different doses and duration of PBM to better elucidate its role in obesity-associated type 2 diabetes development.

Effects of long-term social isolation on central, behavioural and metabolic parameters in middle-aged mice.

Social isolation gained discussion momentum due to the COVID-19 pandemic. Whereas many studies address the effects of long-term social isolation in post-weaning and adolescence and for periods ranging from 4 to 12 weeks, little is known about the repercussions of adult long-term social isolation in middle age. Thus, our aim was to investigate how long-term social isolation can influence metabolic, behavioural, and central nervous system-related areas in middle-aged mice. Adult male C57Bl/6 mice (4 months-old) were randomly divided into Social (2 cages, n = 5/cage) and Isolated (10 cages, n = 1/cage) housing groups, totalizing 30 weeks of social isolation, which ended concomitantly with the onset of middle age of mice. At the end of the trial, metabolic parameters, short-term memory, anxiety-like behaviour, and physical activity were assessed. Immunohistochemistry in the hippocampus (ΔFosB, BDNF, and 8OHDG) and hypothalamus (ΔFosB) was also performed. The Isolated group showed impaired memory along with a decrease in hippocampal ΔFosB at dentate gyrus and in BDNF at CA3. Food intake was also affected, but the direction depended on how it was measured in the Social group (individually or in the group) with no alteration in ΔFosB at the hypothalamus. Physical activity parameters increased with chronic isolation, but in the light cycle (inactive phase), with some evidence of anxiety-like behaviour. Future studies should better explore the timepoint at which the alterations found begin. In conclusion, long-term social isolation in adult mice contributes to alterations in feeding, physical activity pattern, and anxiety-like behaviour. Moreover, short-term memory deficit was associated with lower levels of hippocampal ΔFosB and BDNF in middle age.

Effects of acute exercise on spontaneous physical activity in mice at different ages.

BACKGROUND: Exercise is often used to obtain a negative energy balance. However, its effects on body weight reduction are usually below expectations. One possible explanation is a reduction in spontaneous physical activity (SPA) after exercise since the increase in energy expenditure caused by the exercise session would be offset by the decrease in SPA and its associated energy cost. Thus, we evaluated the effects of a single bout of moderate exercise at individualized intensity on spontaneous physical activity. The impact of the single bout of exercise was determined in early adulthood and at the transition to middle age. METHODS: Male C57bl/6j (n = 10) mice were evaluated at 4 (4 M) and 9 (9 M) months of age. One week after a treadmill Maximal Exercise Capacity Test (MECT), mice performed a 30-min single bout of exercise at 50 % of the maximal speed reached at MECT. An infrared-based system was used to determine locomotor parameters (SPA and average speed of displacement, ASD) before (basal) and immediately after the single bout of exercise for 48 h (D1, 0-24 h; D2, 24-48 h). Food intake was measured simultaneously. Data were analyzed by GEE and statistical significance was set at p < 0.05. RESULTS: Basal SPA declined from 4 M to 9 M (p = 0.01), but maximal exercise capacity was similar. At both ages, SPA and ASD decreased significantly (p < 0.0001) on day 1 after exercise. On D2, SPA returned to basal levels but ASD remained lower than basal (p < 0.001). The magnitude (% of basal) of change in SPA and ASD on D1 and D2 was similar at 4 M and 9 M. Food intake did not change at 4 M but decreased on D2 at 9 M. CONCLUSIONS: A single bout of moderate exercise decreases physical activity in the first 24 h and average speed of locomotion in the 48 h following exercise. This compensation is similar from early adulthood to the transition to middle age. The decrease in both the amount and intensity (speed) of SPA may compensate for the increase in energy expenditure induced by exercise, helping to understand the below-than-expected effect of exercise interventions to cause a negative energy balance.

Insulin Modulates Myogenesis and Muscle Atrophy Resulting From Skin Scald Burn in Young Male Rats.

BACKGROUND: Burn injuries (BIs) due to scalding are one of the most common accidents among children. BIs greater than 40% of total body surface area are considered extensive and result in local and systemic response. We sought to assess morphological and myogenic mechanisms through both short- and long-term intensive insulin therapies that affect the skeletal muscle after extensive skin BI in young rats. MATERIALS AND METHODS: Wistar rats aged 21 d were distributed into four groups: control (C), control with insulin (C + I), scald burn injury (SI), and SI with insulin (SI + I). The SI groups were submitted to a 45% total body surface area burn, and the C + I and SI + I groups received insulin (5 UI/Kg/d) for 4 or 14 d. Glucose tolerance and the homeostatic model assessment of insulin resistance index were determined. Gastrocnemius muscles were analyzed for histopathological, morphometric, and immunohistochemical myogenic parameters (Pax7, MyoD, and MyoG); in addition, the expression of genes related to muscle atrophy (MuRF1 and MAFbx) and its regulation (IGF-1) were also assessed. RESULTS: Short-term treatment with insulin favored muscle regeneration by primary myogenesis and decreased muscle atrophy in animals with BIs, whereas the long-term treatment modulated myogenesis by increasing the MyoD protein. Both treatments improved histopathological parameters and secondary myogenesis by increasing the MyoG protein. CONCLUSIONS: Treatment with insulin benefits myogenic parameters during regeneration and modulates MuRF1, an important mediator of muscle atrophy.

Short time insulin treatment post burn improves elastic-collagen rearrangement and reepithelization.

Extensive burn may cause acute resistance to insulin, which accentuates hypermetabolism, impairs glucose metabolism, immune dysfunction and risks of sepsis. To minimize these effects, insulin is used as a treatment. The purpose was to analyze the collagen-elastic arrangement effects of insulin on the burned skin. Wistar rats were assigned in groups: control (C); control with insulin (C + I); scald burn injury (SBI); and SBI with insulin (SBI+ I). SBI were submitted to 45% total body surface area burn and the insulin-treated groups received insulin (5 UI/Kg/day) for 4 or 14 days (d). Insulin levels, glucose tolerance test and HOMA index were determined. The skin sections were analyzed for histophatological and morphoquantitative data. Histopathological findings showed increased reepithelization of SBI+ I and formation of a new muscle layer after 14 days. In the collagen-elastic arrangement, insulin for 4 days increased the volume fraction (Vv) of thin collagen and elastic fibers. After 14 days, independently of injury, insulin decreased the elastic fibers. Insulin was able to reverse damages in the collagen-elastic rearrangement and stimulate reepithelization after 4 days. Untreated scald-burned animals showed higher Vv of thick collagen after 4 days, while those treated had a higher Vv of thin collagen. The Vv of elastic fibers was increased in SBI+ I for 4 days. In conclusion, insulin treatment was able to stimulate reepithelization. It also reversed the damages to the collagen-elastic arrangement in the scald-burned group, improving the organization of thin collagen and increasing the Vv of elastic fibers in the injured group treated with insulin for a short time, that is, for 4 days.

Nutritional recovery from a low-protein diet during pregnancy does not restore the kinetics of insulin secretion and Ca2+ or alterations in the cAMP/PKA and PLC/PKC pathways in islets from adult rats.

We investigated the insulin release induced by glucose, the Ca2+ oscillatory pattern, and the cyclic AMP (cAMP)/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC) pathways in islets from adult rats that were reared under diets with 17% protein (C) or 6% protein (LP) during gestation, suckling, and after weaning and in rats receiving diets with 6% protein during gestation and 17% protein after birth (R). First-phase glucose-induced insulin secretion was reduced in LP and R islets, and the second phase was partially restored in the R group. Glucose stimulation did not modify intracellular Ca2+ concentration, but it reduced the Ca2+ oscillatory frequency in the R group compared with the C group. Intracellular cAMP concentration was higher and PKA-Cα expression was lower in the R and LP groups compared with the C group. The PKCα content in islets from R rats was lower than that in C and LP rats. Thus, nutritional recovery from a low-protein diet during fetal life did not repair the kinetics of insulin release, impaired Ca2+ handling, and altered the cAMP/PKA and PLC/PKC pathways.

Central and peripheral effects of physical exercise without weight reduction in obese and lean mice.

To investigate the central (hypothalamic) and peripheral effects of exercise without body weight change in diet-induced obesity (DIO). Twelve-week-old male C57Bl/6 mice received a control (C) or a high-fat diet (H). Half of them had free access to running wheels for 5 days/week for 10 weeks (CE) and HE, respectively). Hypothalamic expression of genes related to energy homeostasis, and leptin (Stat3 and p-Stat3) and insulin (Akt and p-Akt) signaling were evaluated. Glucose and leptin tolerance, peripheral insulin sensitivity, and plasma insulin, leptin and adiponectin were determined. Perigonadal and retroperitoneal fat depots were increased by diet but reduced by exercise despite lack of effect of exercise on body weight. Blood glucose during intraperitoneal glucose tolerance test (ipGTT) was higher and glucose decay during intraperitoneal insulin tolerance test (ipITT) was lower in H and HE compared with C and CE. Exercise increased liver p-Akt expression and reduced fast glycemia. High-fat diet increased plasma insulin and leptin. Exercise had no effect on insulin but decreased leptin and increased adiponectin. Leptin inhibited food intake in all groups. Hypothalamic total and p-Stat3 and Akt were similar amongst the groups despite higher plasma levels of leptin and insulin in H and HE mice. High-fat diet modulated gene expression favoring a positive energy balance. Exercise only marginally changed the gene expression. Exercise induced positive changes (decreased fast glycemia and fat depots; increased liver insulin signaling and adiponectin concentration) without weight loss. Thus, despite reducing body weight could bring additional benefits, the effects of exercise must not be overlooked when weight reduction is not achieved.

Spontaneous physical activity and mediators of energy homeostasis in the hypothalamus of mice from 4 to 10 months of age.

NEW FINDINGS: What is the central question of this study? Is the initial decline of spontaneous physical activity (SPA) in mice related to impaired insulin and leptin signalling or brain-derived neurotrophic factor expression in the hypothalamus? What is the main finding and its importance? We showed that SPA started to decline at an early stage, concomitantly with an impairment of hypothalamic leptin signalling. Consequently, energy expenditure decreased and glucose tolerance worsened. Our results demonstrate the need to counteract the initial decline in SPA to avoid metabolic impairments and indicate the possible involvement of central leptin in the reduction in SPA with age. The biological control of physical activity is poorly understood. Age decreases insulin, leptin and brain-derived neurotrophic factor (BDNF) signalling in the hypothalamus, and all have been shown to modulate spontaneous physical activity (SPA). We investigated the age at which SPA starts to decline and whether this is associated with the emergence of hypothalamic insulin and leptin resistance and reduced BDNF expression. Spontaneous physical activity (and other parameters of locomotion) and energy expenditure were determined monthly in mice from the 4th to the 10th month of age. Metabolic and hypothalamic analyses were performed in 4-, 6- and 10-month-old mice. Spontaneous physical activity, distance travelled and speed of locomotion started to decrease in 6-month-old mice. The reduction in SPA became more evident from 8 months of age. Energy expenditure decreased from the 8th month. Hypothalamic BDNF protein expression and insulin signalling did not change throughout the time span studied. Leptin signalling decreased at 6 and 10 months compared with 4 months. Also, compared with 4 months, 6- and 10-month-old mice were glucose intolerant. In conclusion, SPA begins to decline in parallel with reduced hypothalamic leptin signalling. Metabolic impairment also manifests as SPA decreases, highlighting the need to understand the regulation of SPA in order to combat its decline.

Long-term interdisciplinary therapy decreases symptoms of binge eating disorder and prevalence of metabolic syndrome in adults with obesity.

Obesity-associated comorbidities greatly impact the quality and expectancy of life. Binge eating disorder (BED) is the most prevalent eating disorder and it is an important risk factor for obesity and metabolic syndrome (MetS). For these reasons, we aimed to assess the effect of an interdisciplinary therapy on the symptoms of BED and the prevalence of MetS in obese adults. It was hypothesized that the interdisciplinary therapy would decrease symptoms of BED and markers of MetS. Twenty-four volunteers (BMI 34.80±3.17 kg/m2; 41.21±6.28 years old) completed a 32-week intervention. Biochemical characteristics, body composition, the degree of symptoms of binge eating, and macronutrients, and sodium consumption pre- and post-treatment were determined. The prevalence of MetS dropped from 75% to 45.8%, post-therapy. Among the markers of MetS, waist circumference and systolic blood pressure decreased significantly, whereas high-density lipoprotein levels increased. Fasting plasma glucose, diastolic blood pressure, and triglycerides did not change. Based on binge-eating scale (BES) scores, before therapy, 33.3% of volunteers were classified as moderate bingers, and after therapy all volunteers were classified as having no BED symptoms. No difference in the prevalence of MetS between individuals classified as normal or moderate bingers was observed, but we found a positive post-therapy correlation between the BES score and body fat, gynoid fat and trunk fat. Sodium, fat, and carbohydrate consumption decreased. Protein intake did not change. In conclusion, the interdisciplinary approach was efficient in reducing symptoms of BED and MetS prevalence in this population.

The effects of calorie-matched high-fat diet consumption on spontaneous physical activity and development of obesity.

AIMS: To characterize the effects of a calorie matched high-fat diet (HFD) on spontaneous physical activity (SPA), body weight, inflammatory status and expression of genes related to energy homeostasis in hypothalamus of mice. MAIN METHODS: C57Bl/6 mice (n=5 per group) were fed a control diet (16.5% calories from fat) - control group (C), or a calorie matched HFD (60% calories from fat). We evaluated, periodically, body weight and SPA by infrared beam sensors and, at the end of the 12th week, we verified blood glucose levels, fat pads weight, plasma insulin, TNF-α and IL-6 by ELISA and the hypothalamic expression of 84 genes related to energy homeostasis, by quantitative real-time PCR array. KEY FINDINGS: Isocaloric HFD reduced SPA already in the first 48h and SPA was kept lower in the HFD compared to C throughout. These changes resulted in an increase in body weight, adiposity, TNF-α and IL-6, blood glucose and hyperinsulinemia in the HFD group when compared to the C group. Expression of the Agrp, Bdnf, Adra2b and Pyy genes were altered in the hypothalamus of HFD-fed mice, highlighting the downregulation of Bdnf, key regulator of energy homeostasis. SIGNIFICANCE: Dietary macronutrient distribution plays an important part in energy homeostasis that goes beyond its energy content. Despite calorie-matched, the HFD led to increased body weight and adiposity due to decreased SPA, highlighting the key role of SPA on energy balance. The changes in hypothalamic gene expression seem to underlie the reduction in SPA caused by HFD.

Voluntary running decreases nonexercise activity in lean and diet-induced obese mice.

PURPOSE: Determine whether voluntary wheel running triggers compensatory changes in nonexercise activity in lean and high-fat diet fed mice. METHODS: C57Bl/6 mice received a control (C) or a high-fat diet (H) and half of them had free access to a running wheel 5days/week (CE and HE, respectively) for 10weeks. Energy intake, nonexercise activity (global activity, distance covered and average speed of displacement in the home cage) and energy expenditure (EE) were evaluated at weeks 5 and 10 during the 2days without the wheels. RESULTS: High-fat diet increased weight gain in H (110%) and HE (60%) groups compared to C and CE groups, respectively, with no effect of exercise. Wheel running increased energy intake (26% CE, 11% HE in week 5; 7% CE, 45% HE in week 10) and decreased distance covered (26% for both CE and HE in week 5; 35% CE and 13% HE in week 10) and average speed (35% CE and 13% HE in week 5; 45% CE and 18% HE in week 10) compared to the respective nonexercised groups. In week 10 there was an interaction between diet and exercise for global activity, which was reduced nearly 18% in CE, H, and HE groups compared to C. Access to a running wheel increased EE in week 5 (11% CE and 16% HE) but not in week 10, which is consistent with the period of highest running (number of turns: weeks 1-5 nearly 100%>weeks 6-10 for CE and HE groups). EE was reduced in H (19%) and HE (12%) groups compared to C and CE, in week 10. CONCLUSION: Voluntary running causes a compensatory decrease in nonexercise activity and an increase in energy intake, both contributing to the lack of effect of exercise on body mass.

Peer mentoring program in an interprofessional and interdisciplinary curriculum in Brazil.

The Federal University of São Paulo, Baixada Santista Campus was founded in 2006 with five degree-granting programs in physical education, physiotherapy, nutrition, psychology, and occupational therapy. The guiding principle behind the programs' educational mission was centered on the development of health care professionals capable of working in interdisciplinary teams with an emphasis on holistic patient care. This pedagogical structure required peer-mentoring programs in order to integrate different areas of knowledge and to improve learning strategies among new generations of students. The authors' objective in the present report is to discuss the strategies and activities of the peer-mentoring program in histophysiology and gross anatomy in an interdisciplinary and interprofessional curriculum. Evaluations by students, mentors and professors are presented, along with a statistical analysis of variance comparing student performance in the module assessments according to their participation in the peer-mentoring activities. The results demonstrated that students who participated in peer-mentoring activities enjoyed a higher rate of academic success than those who did not participate. In addition, student and mentor evaluations of the peer mentoring program were highly positive. The program enabled mentors to gain a deeper knowledge of the subjects addressed in the learning modules, as well as to develop intrinsic teaching skills during their time as mentors. In short, the authors believe that the peer-mentoring program has been validated for its effectiveness in raising student academic performance.

Mechanisms of insulin secretion in malnutrition: modulation by amino acids in rodent models.

Protein restriction at early stages of life reduces ß-cell volume, number of insulin-containing granules, insulin content and release by pancreatic islets in response to glucose and other secretagogues, abnormalities similar to those seen in type 2 diabetes. Amino acids are capable to directly modulate insulin secretion and/or contribute to the maintenance of ß-cell function, resulting in an improvement of insulin release. Animal models of protein malnutrition have provided important insights into the adaptive mechanisms involved in insulin secretion in malnutrition. In this review, we discuss studies focusing on the modulation of insulin secretion by amino acids, specially leucine and taurine, in rodent models of protein malnutrition. Leucine supplementation increases insulin secretion by pancreatic islets in malnourished mice. This effect is at least in part due to increase in the expression of proteins involved in the secretion process, and the activation of the PI3K/PKB/mTOR pathway seems also to contribute. Mice supplemented with taurine have increased insulin content and secretion as well as increased expression of genes essential for ß-cell functionality. The knowledge of the mechanisms through which amino acids act on pancreatic ß-cells to stimulate insulin secretion is of interest for clinical medicine. It can reveal new targets for the development of drugs toward the treatment of endocrine diseases, in special type 2 diabetes.

Effects of exercise training on hippocampus concentrations of insulin and IGF-1 in diabetic rats.

The present study investigated the role of swimming training on cerebral metabolism and hippocampus concentrations of insulin and IGF-1 in diabetic rats. Wistar rats were divided in sedentary control (SC), trained control (TC), sedentary diabetic (SD), and trained diabetic (TD). Diabetes was induced by Alloxan (35 mg kg(-1) b.w.). Training program consisted in swimming 5 days/week, 1 h/day, 8 weeks, supporting a load corresponding to 90% of maximal lactate steady state (MLSS). For MLSS determination, rats were submitted to three sessions of 25-min supporting loads of 4, 5, or 6% of body wt, with intervals of 1 week. Blood samples were collected every 5 min for lactate determination. An acute exercise test (25 min to 90% of MLSS) was done in 7th week to confirm the efficacy of training. All dependent variables were analyzed by one-way analysis of variance (ANOVA) and a significance level of P < 0.05 was used for all comparisons. The Bonferroni test was used for post hoc comparisons. At the end of the training period, rats were sacrificed and sample blood was collected for determinations of serum glucose, insulin, GH, and IGF-1. Samples of gastrocnemius muscle and liver were removed to evaluate glycogen content. Hippocampus was extracted to determinate glycogen, insulin, and IGF-1 contents. Diabetes decreased serum GH, IGF-1, and liver glycogen stores in SD. Diabetes also increased hippocampus glycogen and reduced hippocampus IGF-1 content. Physical training recovered liver and hippocampus glycogen stores and promoted increases in serum IGF-1 in TD group. Physical training restored hippocampus IGF-1 content in diabetic group. It was concluded that in diabetic rats, physical training induces important metabolic and hormonal alterations that are associated with an improvement in glucose homeostasis and with an increased activity in the systemic and hippocampus IGF-1 peptide.

Exercise test and glucose homeostasis in rats treated with alloxan during the neonatal period or fed a high calorie diet.

BACKGROUND: Animal models appear well-suited for studies into the role of exercise in the prevention of non-insulin-dependent diabetes mellitus (NIDDM). The aim of the present study was to analyze glucose homeostasis and blood lactate during an exercise swimming test in rats treated with alloxan during the neonatal period and/or fed a high calorie diet from weaning onwards. METHODS: Rats were injected with alloxan (200 mg/kg, i.p.) or vehicle (citrate buffer) at 6 days of age. After weaning, rats were divided into four groups and fed either a balanced diet or a high-caloric diet as follows: C, control group (vehicle + normal diet); A, alloxan-treated rats fed the normal diet; H, vehicle-treated rats fed the high-caloric diet; and HA, alloxan-treated rats fed the high-caloric diet. RESULTS: Fasting serum glucose levels were higher in groups A and AH compared with the control group. The Homeostatic Model Assessment index varied in the groups as follows: H>A>HA = C. There were no differences in free fatty acids or blood lactate concentrations during the swim test. CONCLUSIONS: Alloxan-treated rats fed a normal or high-caloric diet have the potential to be used in studies analyzing the role physical exercise plays in the prevention of NIDDM.

Exercise training in the aerobic/anaerobic metabolic transition prevents glucose intolerance in alloxan-treated rats.

BACKGROUND: Ninety percent of cases of diabetes are of the slowly evolving non-insulin-dependent type, or Type 2 diabetes. Lack of exercise is regarded as one of the main causes of this disorder. In this study we analyzed the effects of physical exercise on glucose homeostasis in adult rats with type 2 diabetes induced by a neonatal injection of alloxan. METHODS: Female Wistar rats aged 6 days were injected with either 250 mg/kg of body weight of alloxan or citrate buffer 0.01 M (controls). After weaning, half of the animals in each group were subjected to physical training adjusted to meet the aerobic-anaerobic metabolic transition by swimming 1 h/day for 5 days a week with weight overloads. The necessary overload used was set and periodically readjusted for each rat through effort tests based on the maximal lactate steady state procedure. When aged 28, 60, 90, and 120 days, the rats underwent glucose tolerance tests (GTT) and their peripheral insulin sensitivity was evaluated using the HOMA index. RESULTS: The area under the serum glucose curve obtained through GTT was always higher in alloxan-treated animals than in controls. A decrease in this area was observed in trained alloxan-treated rats at 90 and 120 days old compared with non-trained animals. At 90 days old the trained controls showed lower HOMA indices than the non-trained controls. CONCLUSION: Neonatal administration of alloxan induced a persistent glucose intolerance in all injected rats, which was successfully counteracted by physical training in the aerobic/anaerobic metabolic transition.

Diabetes evolution in rats after neonatal treatment with alloxan.

Physical exercises have been recommended in the prevention of non-insulin dependent diabetes mellitus (NIDDM), but the mechanisms involved in this intervention are not yet fully understood. Experimental models offer the opportunity for the study of this matter. The present study was designed to analyze the diabetes evolution in rats submitted to neonatal treatment with alloxan with the objective of verifying the suitability of the model to future studies with exercises. For this, newly born rats (6 days old) received intraperitoneal alloxan (A=200 mg/kg of body weight). Rats injected with vehicle (citrate buffer) were used as controls (C). The fasting blood glucose level (mg/dL) was higher in the alloxan group at the day 28 (C=47.25 +/- 5.08; A=54.51 +/- 7.03) but not at the 60 day of age (C=69.18 +/- 8.31; A=66.81 +/- 6.08). The alloxan group presented higher blood glucose level during glucose tolerance test (GTT) (mg/dL. 120 min) in relation to the control group both at day 28 (C=16908.9 +/- 1078.8; A=21737.7 +/- 1106.4) and at day 60 (C=11463.45 +/- 655.30; A=15282.21 +/- 1221.84). Insulinaemia during GTT (ng/mL. 120 min) was lower at day 28 (C=158.67 +/- 33.34; A=123.90 +/- 19.80), but presented no difference at day 60 (C=118.83 +/- 26.02; A=97.88 +/- 10.88). At day 60, the glycogen concentration in the soleus muscle (mg/100 mg) was lower in the alloxan group (0.3 +/- 0.13) in relation to the control group (0.5 +/- 0.07). No difference was observed between groups in relation to (micromol/g.h): Glucose Uptake (C=5.8 +/- 0.63; A=5.2 +/- 0.73); Glucose Oxidation (C=4.3 +/- 1.13; A=3.9 +/- 0.44); Glycogen Synthesis (C=0.8 +/- 0.18; A=0.7 +/- 0.18) and Lactate Production (C=3.8 +/- 0.8; A=3.8 +/- 0.7) by the isolated soleus muscle. The glucose-stimulated insulin secretion (16.7mM) by the isolated islets (ng/5 islets. h) of the alloxan group was lower (14.3 +/- 4.7) than the control group (32.0 +/- 7.9). Thus, we may conclude that this neonatal diabetes induction model gathers interesting characteristics and may be useful for further studies on the role of the exercise in the diabetes mellitus appearance.