| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physical Education, UNESP, São Paulo State University, Rio Claro, São Paulo, Brazil
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
(Received 4 June 2004;
accepted after revision 17 September 2004; first published online 4 October 2004)
Corresponding author C. A. Machado de Oliveira: Avenue. 24 A, 1515, Departamento de Educação Física, IB, UNESP Universidade Estadual Paulista, Rio Claro, Sao Paulo, Brazil. E-mail: camo{at}rc.unesp.br
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Kodama et al. (1993) developed a less severe diabetes model through the neonatal administration of alloxan in rats. However, according to the same authors, more studies are necessary to verify whether or not this model has the characteristics of non-insulin-dependent diabetes mellitus (NIDDM).
The lack of insulin effects in diabetes mellitus has been long known. Some mild cases of diabetes can be treated with special diet and exercise, without the need for insulin. Physical activity increases glucose uptake by cells, in normal and insulin-resistent people, even if its concentration is low. Exercise is responsible for many skeletal muscle adaptations that contribute to this alteration, including a rise in Glut4 protein expression, enzymatic capacity and muscle capilarization (Borghouts & Keizer, 2000). As muscle represents 40% of body mass, muscular activity is very important to blood glucose control and diabetes prevention (Weineck, 1999).
Furthermore, recent epidemiological studies have provided evidence that the level of physical activity is negatively correlated with the incidence of NIDDM (Folsom et al. 2000; Zinman et al. 2003). Kuwajima et al. (1999), utilizing genetically modified animals (rats which develop obesity and glucose intolerance at 10 weeks old), also showed the prophylactic effect of physical activity with respect to the development of NIDDM.
Hence, the aim of the present study was to analyse the effects of the neonatal administration of alloxan in rats and to verify whether aerobic exercise modulates the long-term metabolic manifestations of the drug.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The studies were carried out on male Wistar rats, maintained at 25 ± 1°C on a 12-h light–dark cycle, with free access to standard rat chow and water. All experiments with the animals were performed in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Council of Europe no123, Strasbourg, 1985).
Neonatal alloxan administration
At 2 days old, the male pups, with a body weight of 5.32 ± 0.31 g, received alloxan monohydrate injection (Sigma-Aldrich Inc., St Louis, MO, USA) dissolved in citrate buffer 0.01 M, pH 4.5 (200 mg (kg body weight)–1; intraperitoneally), after a 16-h fast. As controls, we utilized same-age, vehicle-injected (citrate buffer) rats. Immediately, the young were distributed in such a way that each mother suckled eight pups.
Experimental groups
At 28 days old, the animals were randomly divided into three groups and remained in treatment until 90 days old: controls (C), sedentary citrate buffer-injected rats; alloxan (A), sedentary alloxan-injected rats; and alloxan/trained (AT), alloxan-injected rats subjected to exercise.
Exercise
The exercise protocol consisted of swimming for 1 h day–1, 5 days week–1, with a 3% body weight overload in a swimming pool filled with water at 32 ± 1°C. This exercise protocol was selected because in previous studies we demonstrated that it corresponds to moderate aerobic exercise training for rats (Gobatto et al. 2001).
Initial assessments
Body weight and food and water intake. All the animals had body weight and food and water intake recorded once a week. The results are shown as cumulative body weight gain and daily intake of food and water curves. The areas under body weight (g (10 weeks)–1), food intake (g chow (100 g body weight)–1 (10 weeks)–1) and water intake curves (ml water (100 g body weight)–1 (10 weeks)–1) were calculated by the trapezoidal method (Mathews et al. 1990), using the software Origin 6.0 (1999).
Blood glucose. The confirmation of the diabetogenic effect of alloxan was made at when the rats were 28, 60 and 90 days old, by the determination of fasting (after a 15-h fast) and non-fasting blood glucose levels (30 min after administration of glucose solution, 2.0 g (kg body weight)–1, into the stomach through a gastric catheter). Blood samples (25 µl) were obtained from a cut in the tip of the tail and determined by the glucose oxidase colorimetric enzymatic method (Laborlab Kit, Guarulhos, Sao Paulo, Brazil).
Oral glucose tolerance test (GTTo). Rats were fasted for 15 h, at 28, 60 and 90 days old. Glucose (200 g l–1) was administered into the stomach of the rats through a gastric catheter at the final dose of 2.0 g (kg body weight)–1. Blood samples for determination of serum glucose (25 µl) and insulin (75 µl) levels were obtained from a cut in the tip of the tail at 0, 30, 60 and 90 min. Blood glucose level was determined by the glucose-oxidase method, and insulin level by radioimmunoassay (Herbert et al. 1965). The blood glucose and insulin responses during the GTTo were evaluated by the total areas under the serum glucose (mM (90 min)–1) and insulin (nM (90 min)–1) curves using the trapezoidal method (Mathews et al. 1990), using the software Origin 6.0 (1999).
Subcutaneous insulin tolerance test (ITTsc).
Subcutaneous insulin tolerance tests (ITTsc) were also performed in the rats at 28, 60 and 90 days old. The ITTsc consisted of a bolus injection of regular insulin at the dorsal region (30 mU (g body weight)–1). Blood samples (25 µl) were obtained from a cut in the tip of the tail at 0, 30, 60 and 90 min for determination of serum glucose level by the glucose-oxidase method (Latorraca et al. 1998). A constant for serum glucose disappearance (Kitt = % min–1), was calculated from the formula 0.693/t
. The serum glucose t was calculated from the slope of the least square analysis of serum glucose concentration from 0 to 30 min after insulin injection, when serum glucose concentration decreased linearly (Lundbaek, 1962).
Further assessments
At 90 days old, all the animals were killed by decapitation 48 h after the last tolerance test (without previous fasting and 48 h after the last exercise session in the trained rats), for biological material collection.
Blood assessments. Blood samples were collected for evaluation of glucose, total protein (Laborlab Kit), and free fatty acid (FFA) levels (Nogueira et al. 1990) by colorimetric methods, and insulin level by radioimmunoassay (Herbert et al. 1965).
Tissue assessments. Liver, soleus muscle, left epididymal adipose tissue and pancreas were completely excised and weighed. In these tissues, the total protein (Lowry et al. 1951) and DNA (Giles & Myers, 1965) contents were assessed, to infer the cell number (DNA) and size (protein/DNA ratio) according to Winick et al. (1972). In the liver, lipid (Nogueira et al. 1990) and glycogen concentrations (Dubois et al. 1956) were also determined. In the muscle, the glycogen content and the ‘in vitro’ glucose uptake were measured. In the pancreas, insulin content and ‘in vitro’ insulin secretion by isolated islets were evaluated.
Glucose uptake by the soleus muscle. Longitudinal strips from the soleus muscle (25–35 mg) were first incubated for 30 min at 37°C in 1.5 ml of a Krebs bicarbonate medium (composition in g l–1: NaCl 6.0; Hepes 1.6; KCl 0.32; CaCl2 0.12; KH2PO4 0.15; NaHCO3 1.9; MgSO4 0.3) balanced with a mixture of 95% O2–5% CO2 at pH 7.4. After this time, the muscle strips were transferred to glass scintilation vials containing 1.5 ml of Krebs bicarbonate buffer supplemented with glucose 5.5 mM (with [3H]2-deoxyglucose (2DG; 0.5 µCi ml–1)) and insulin (100 µU ml–1). Glucose uptake ([3H]2-DG) by the incubated muscle was measured after digestion in 0.5 ml of KOH 1 N for 20 min. From this medium, a 50 µl sample was collected and added to a vial containing 10 ml scintillation liquid, in order to perform the [3H] counting, in Beta counter (Tri Carb 2100 TR – Packard) (Mello et al. 2001).
Insulin secretion by isolated islets. To measure insulin secretion, groups of five islets isolated by collagenase digestion (Lacy & Kostianovsky, 1967) were incubated for 30 min at 37°C, in Krebs bicarbonate medium containing glucose (5.6 mM), supplemented with bovine serum albumin (3 g l–1) and balanced with a mixture of 95% O2–5% CO2; pH 7.4. The solution was then replaced by fresh buffer, and the islets were incubated for a further hour with different glucose concentrations (2.8, 5.6 and 16.7 mm). The insulin content of the medium at the end of the incubation period was determined by radioimmunoassay (Herbert et al. 1965).
Pancreatic insulin extraction. Initially, 0.2 g of tissue was collected in vials containing 2 ml of 1 N HCl. The material was incubated in a stove at 40°C for 24 h. The extracted material was diluted 1: 5000 in 0.25% bovine serum albumin, in borate buffer at pH 5.5. The insulin content of the extracted material was measured by the radioimmunoassay method (Herbert et al. 1965).
Statistics
The results are shown as mean ± standard deviation and were analysed statistically by one-way ANOVA followed by Newman–Keuls test. A level of 5% was taken as the level of statistical significance.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
|
|
|
Values referring to analyses made in the pancreas, liver, soleus muscle and epididymal adipose tissue after kill (90 days) are shown in Table 2. The groups that received alloxan at 2 days old (A and AT) had markedly reduced pancreatic insulin levels compared to the control group. There was no alteration in protein level in this organ among the groups. The DNA content of pancreas was increased in A and AT groups. Thus, the protein/DNA ratio of the animals that received drug treatment (A and AT) was lower than the control group (Table 2).
|
Muscle glycogen concentration was higher in AT group than in the other groups (C and A). Protein level was reduced in the A rats and DNA content was greater in both A and AT than in controls (C). The alloxan-injected groups (A and AT) showed lower values of muscle protein/DNA ratio than the control group.
The epididymal adipose tissue total weight was reduced in both A and AT groups than in the C group, and also in AT animals compared to A animals. Protein levels of the adipose tissue was altered (reduction) only in the AT group. The DNA content of the adipose tissue followed the same pattern observed in the other organs evaluated in the present study: increase in the A and AT groups in relation to the C group. A reduction in the protein/DNA ratio in AT animals was noted when compared to the other animals (Table 2).
The static insulin secretion by the pancreatic islets of the animals after they had been killed was similar among the groups at 2.8 and 5.6 mM of glucose, as shown in Table 3. However at 16.7 mM glucose, the AT group had a stronger response than the others (C and A), as indicated by the increased insulin secretion. Glucose uptake by the isolated soleus muscle was not different among the studied groups (Table 3).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Kodama et al. (1993) observed that Sprague-Dawley rats treated at the same age and with the same dose of alloxan as the animals of this study, did not show any alteration either in body weight or in water intake. Similar results were obtained in the present study. Although Kodama et al. (1993) had found reduced food intake in the treated rats, this phenomenon was not noticed by us. Once the food intake of the AT group was similar to other groups and their energy expenditure was increased due to exercise, the final result was a reduction in body weight in these animals. The physical activity also resulted in greater water intake by this group.
The GTTo performed on the 28th day showed that alloxan, as expected, caused a rise in the blood glucose concentration in the A rats. From this moment on, a programme of exercise was introduced one group of these animals (AT group). In the GTTo at 60 days, exercise had a beneficial effect on the AT group, as the area under the blood glucose curve of this group was similar to the control group, whereas blood glucose levels remained increased in the A animals, compared to C and AT rats. Studies had shown that there is an up-regulation in the mRNA expression as well as the Glut-4 protein expression in the muscle of trained rats (Lee et al. 2002). In addition, the increase either in the production of nitric oxide or in the proportion of nutritive capillary flow in muscle tissue during exercise contributes to increased glucose disposal from the circulation (Sakamoto et al. 1998). Hence, the reduction in the blood glucose levels of our AT rats could have been mediated by a rise in the number of glucose transporters, or also by a greater peripheral sensibility to insulin caused by exercise (Borghouts & Keizer, 2000; Lee et al. 2002). In the GTTo performed on the 90th day, there was a recovery from the blood glucose alterations induced by alloxan in the A animals. However, the AT group had a higher blood glucose level than the other groups (C and A). On the other hand, after the animals had been killed, blood glucose did not differ among the studied groups.
Evaluation of serum insulin level during the GTTo showed that alterations occurred only at 28 days. The fasting insulinaemia of the animals treated with alloxan was 56% lower than the control group. However, after glucose overload it increased continuously, reaching twice the values of the C animals at 90 min (data not shown). Due to this extreme difference between fasting insulinaemia and insulinaemia 90 min after glucose overload, we did not find any change in the area under insulin curve at this time. At 60 and 90 days, the serum levels of this hormone did not differ among the groups. The same occurred at the moment the rats were killed, explaining the similar levels of glucose and serum total proteins among all groups. On the other hand, pancreatic insulin content of the animals of both alloxan-treated groups (A and AT) was smaller (34% and 49%, respectively) than the control animals. Taken together, these data corroborate the results of Portha et al. (1989), using 8-week-old Wistar rats, treated with streptozotocin on the day of birth or 2 days after. According to these authors, some days after streptozotocin administration, a drop of aproximately 93% of the pancreatic insulin stores occurred. From this phase on, ß-cells regenerated spontaneously, by replication and/or neogenesis (Bonnerweir & Smith, 1994), reaching 50% of the value found in control rats (Portha et al. 1989).
Furthermore, the static insulin secretion by isolated islets was greater in the trained animals at the highest glucose concentration (16.7 mM). Shima et al. (1994) reported that islets forced to secrete more insulin, can suffer injury and die. This would lead, with time, to the elevated levels of blood glucose observed in the GTTo of the AT group and, consequently, to the organic impairment caused by diabetes.
The high FFA serum levels found in our animals treated with alloxan (A and AT) are in agreement with the previous reports of Straczkowski et al. (2000), using streptozotocin-induced diabetic rats, and simulate the metabolic alteration present in diabetic people (Borghouts & Keizer, 2000). According to Straczkowski et al. (2000), the inhibition of lipolysis by insulin is impaired, leading to this picture. Corroborating this hypothesis, the total weight of the epididymal adipose tissue appeared lower in the animals that received the diabetogenic drug than in control animals. High levels of FFAs are harmful to glucose homeostasis, causing inhibition of insulin biosynthesis and secretion by the ß-cells (Yaney & Corkey, 2003), and even leading ß-cells to apoptosis (Haber et al. 2002). FFAs also inhibit the enzyme responsible for the insulin degradation in the liver, which would lead to hyperinsulinaemia and, consequently, insulin resistance (Hamel et al. 2003). FFAs also interfere in actions mediated by insulin, such as the inhibition of the high blood glucose-induced suppression of endogenous glucose production (Krebs et al. 2001). In the muscle, FFA causes reduction in glucose uptake, blunts the rise in intramuscular glucose-6-phosphate (G6P), inhibits the parallel increase of intramuscular inorganic phosphate (Krebs et al. 2001; Haber et al. 2002) and reduces the phosphorylation of the insulin receptor (IR) and insulin substrate receptor 1 (IRS-1), resulting in peripheral resistance to the hormone (Haber et al. 2002). These alterations are seen as potentially responsible by the onset of NIDDM (Haber et al. 2002; Hamel et al. 2003; Yaney & Corkey, 2003). As FFA is utilized as fuel, this would explain its reduction in the AT group. In addition, according to Straczkowski et al. (2000), moderate physical exercise stimulates lipolysis in the adipose tissue. This could lead to reduction in protein content, protein/DNA ratio (cellular size index, according to Winick et al. 1972) and weight of adipose tissue observed in our alloxan-treated/trained animals compared to the sedentary ones. Reduction in body fat as a consequence of exercise has been described in the literature (Tancréde et al. 1982; Shima et al. 1994; Harada et al. 2002), and it is an important benefit of physical activity.
Exercise also resulted in a higher utilization of liver lipid and glycogen, reducing the stocks in this tissue. These alterations might be responsible for the reduction in the protein/DNA ratio of the hepatic cells in the AT group compared to C and A groups.
It was surprising to find in the present study that exercise did not improve the insulin sensitivity throughout the experimental period, as shown by the glucose uptake by the isolated soleus muscle of the animals at 90 days and the glucose disappearance index (Kitt) results. On the contrary, on the 60th day the Kitt of the AT animals was lower than the A animals, although the blood glucose concentration of the trained group was lower. Thus, the elevated muscle glycogen content found in trained rats is probably due to the higher availability of FFAs, saving muscle glycogen (Luciano & Mello, 1998; Santos et al. 2000).
Alloxan reduced the soleus muscle protein content of the A animals. As insulin plays a fundamental role in the entry of amino acids into the cells, stimulating protein synthesis and inhibiting proteolysis (Luciano & Mello, 1998), the reduction in the secretion of this hormone or the resistence to its action can account for this result. The exercise programme utilized in the present study was efficient in avoiding this alteration.
An interesting result of the neonatal alloxan administration found in our study was the increase in DNA content in all the organs assessed: pancreas, liver, muscle and epididymal adipose tissue (except for liver in A group). Exercise did not interfere with this finding. It is known that organ growth by hyperplasia (increase in DNA content) in the rat, although varying according to the tissue studied, still occurs some time after birth, but ceases soon afterwards (Winick et al. 1972). In the present study, exercise was performed only after the rats were 28 days old, when this type of growth had probably already ceased in the organs examined. Therefore, exercise was not able to interfere in this process. This rise in DNA content led to a lower protein/DNA ratio in most of the evaluated tissue in the alloxan-treated rats, whether or not subjected to exercise, than in controls.
In conclusion, although the elevation in blood glucose level is transitory in the A animals, some blood and tissue alterations remain and can be harmful to the maintenance of homeostasis. The rehabilitation caused by the exercise was only partial. Physical exercise only partially counteracted these alterations. Furthermore, training worsened glucose tolerance at the 90th day, suggesting that the exercise intensity should be adjusted to the diabetic condition.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Balamurugan AN, Gu Y, Miyamoto M, Wang W, Inoue K & Tabata Y (2003). Streptozotocin (STZ) is commonly used to induce diabetes in animal models. Pancreas 26, 102–103.[CrossRef][Medline]
Bonnerweir S & Smith FE (1994). Islet cell growth and the growth factors involved. Trends Endocrinol Metab 5, 60–64.[Medline]
Borghouts LB & Keizer HA (2000). Exercise and insulin sensitivity: a review. Int J Sports Med 21, 1–12.[CrossRef][Medline]
Dubois B, Gilles KA, Hamilton JK & Rebers PA (1956). Calorimetric method for determination of sugar and related substances. Anal Chem 28, 350–356.[CrossRef]
Folsom AR, Kushi LH & Hong C (2000). Physical activity and incidenct diabetes mellitus in postmenopausal women. Am J Public Health 90, 134–138.
Giles KW & Myers A (1965). An improved diphenylamine method for the estimation of deoxyribonucleic acid. Nature 206, 93.[Medline]
Gobatto CA, Mello MAR, Sibuya CY, Azevedo JRM, Santos LA & Kokubun E (2001). Maximal lactate steady state in rats submitted to swimming exercise. Comp Biochem Physiol 130, 21–27.
Haber EP, Ximenes HMA, Procópio J, Carvalho CRO, Curi R & Carpinelli AR (2002). Pleiotropic effects of fatty acids on pancreatic beta-cells. J Cell Physiol 194, 1–12.
Hamel FG, Upward JL & Bennett RG (2003). In vitro inhibition of insulin-degrading enzyme by long-chain fatty acids and their coenzyme a thioesters. Endocrinology 144, 2404–2408.
Harada N, Takishita E, Ishimura N, Minami A, Sakamoto S & Nakaya Y (2002). Combined effect of ace inhibitor and exercise training on insulin resistance in type 2 diabetic rats. Life Sci 70, 1811–1820.[CrossRef][Medline]
Herbert V, Lau KS, Gotlieb CW & Bleicher ST (1965). Coated charcoals immunoassay of insulin. J Clin Endocrinol Metab 25, 1375–1384.[Medline]
Iwase M, Nunoi K, Sadoshima S, Kikuchi M & Fujishima M (1989). Liver, kidney and islet cell tumors in spontaneously hypertensive and normotensive rats treated neonatally with streptozotocin. Tohoku J Exp Med 159, 83–90.[Medline]
Iwase M, Nunoi K, Wakisaka M, Kikuchi M, Maki Y, Sadoshima S & Fujishima M (1991). Spontaneous recovery from non-insulin-dependent diabetes mellitus induced by neonatal streptozotocin treatment in spontaneously hypertensive rats. Metabolism 40, 10–14.[CrossRef][Medline]
Kazumi T, Yoshino G, Fujii S & Baba S (1978). Tumorigenic action of streptozotocin on the pancreas and kidney in male Wistar rats. Cancer Res 38, 2144–2147.
Kodama T, Iwase M, Nunoi K, Maki Y, Yoshinari M & Fujishima M (1993). A new diabetes model induced by neonatal alloxan treatment in rats. Diabetes Res Clin Pract 20, 183–189.[CrossRef][Medline]
Krebs M, Krssak M & Nowotny P (2001). Free fatty acids inhibit the glucose-stimulated increase of intramuscular glucose-6-phosphate concentration in man. Diabetes 50 (Suppl. 2), A25.
Kuwajima M, Kuroda I, Mizuno A, Murakami T & Shima K (1999). The preventive effect of caloric restrition and exercise training on the onset of NIDDM in a rat model. Nutr Res 19, 401–413.[CrossRef]
Lacy PE & Kostianovsky M (1967). Method for isolation of the intact islets of Langerhans from the rat pancreas. Diabetes 16, 35.[Medline]
Latorraca MQ, Carneiro EM, Boschero AC & Mello MAR (1998). Protein deficiency during pregnancy and lactation impairs glucose induced insulin secretion but increases the sensivity to insulin in weaned rats. Br J Nutr 80, 291–297.[Medline]
Lee JS, Bruce CR, Tunstall RJ, Cameron-Smith D, Hügel H & Hawley A (2002). Interaction of exercise and diet on glut-4 protein and gene expression in type I and type II rat skeletal muscle. Acta Physiol Scand 175, 37–44.[CrossRef][Medline]
Lowry OH, Rosebrough NJ, Farr AL & Randall RJ (1951). Protein measurement with the folin phenol reagent. J Biol Chem 193, 265–275.
Luciano E & Mello MAR (1998). Atividade física e metabolismo de proteínas em músculo de ratos diabéticos experimentais. Rev Paul Educ Fís 2, 202–209.
Lundbaek K (1962). Intravenous glucose tolerance as a tool in definition and diagnosis of diabetes mellitus. Br Med J 3, 1507–1513.
Mathews JNS, Altman DG, Campbell MJ & Royston P (1990). Analysis of serial measurements in medical research. Br Med J 27, 230–235.
Mauer SM, Lee CS, Najarian JS & Brown DM (1974). Induction of malignant kidney tumors in rats with streptozotocin. Cancer Res 34, 158–160.
Mello MAR, Souza CT, Braga LR, Santos JW, Ribeiro IA & Gobatto CA (2001). Glucose tolerance and insulin action in monosodium glutamate obese exercise-trained rats. Physiol Chem Phys Med NMR 33, 63–71.[Medline]
Nogueira DM, Strufaldi B, Hirata MH, Abdalla DSP & Hirata RDC (1990). Sangue-Parte I: Glicídios. In Métodos de Bioquímica Clínica, ed. Nogueira DM, Strufaldi B, Hirata MH, Abdalla DSP & Hirata RDC, pp. 153–168. São Paulo.
Portha B, Blondel O, Serradas P, Evoy R, Giroix MH, Kergoat M & Bailbe D (1989). The rat models of non-insulin dependent diabetes induced by neonatal streptozotocin. Diabetes Metab31, 61–75.
Sakamoto S, Minami K, Niwa Y, Ohnaka M, Nakaya Y, Mizuno A, Kuwajima M & Shima K (1998). Effect of exercise training and food restriction on endothelium-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous NIDDM. Diabetes 47, 82–86.[Abstract]
Santos JW, Luciano E & Mello MAR (2000). Treinamento aeróbio e prevenção da diabetes induzida por aloxana em ratos. Rev Bras Ativ Fís Saúde 5, 31–41.
Shima K, Shi K, Mizuno A, Sano T, Ishida K & Yoshimoto S (1994). Effects of difference in amount of exercise training on prevention of diabetes mellitus in the Otsuka-Long-Evans-Tokushima Fatty rats, a model of spontaneous non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 23, 147–154.[CrossRef][Medline]
Steiner H, Oelz O, Zahnd G & Froesch ER (1970). Studies on islet cell regeneration, hyperplasia and intrainsular cellular interrelations in long lasting streptozotocin diabetes in rats. Diabetologia 6, 558–564.[CrossRef][Medline]
Straczkowski M, Kowalska I, Górski J & Kinalska I (2000). The effect of a single bout of exhaustive exercise on muscle carbohydrate and lipid metabolism in a rat model of type 2 diabetes mellitus. Acta Diabetologica 37, 47–53.[CrossRef][Medline]
Tancréde G, Rousseau-Migneron S & Nadeau A (1982). Beneficial effects of physical training in rats with a mild streptozotocin-induced diabetes mellitus. Diabetes 31, 406–409.[Abstract]
Weineck J (1999). Treinamento para manutenção da saúde. In Treinamento Ideal: Instruções Técnicas Sobre O Desempenho Fisiológico, incluindo considerações específicas de treinamento infantil e juvenil, 9th edn, ed. Weineck J, pp. 651–662. São Paulo.
Winick M, Basel JA & Rosso P (1972). A nutrition and cell growth. In Nutrition & Development, ed. Winick M, pp. 49–97. John Wiley & Sons, New York.
Yamagami T, Miwa A, Takasawa S, Yamamoto H & Okamoto H (1985). Induction of rat pancreatic B-cell tumors by the combined administration of streptozotocin or alloxan and poly (adenosine diphosphate ribose) synthetase inhibitors. Cancer Res 45, 1845–1849.
Yaney GC & Corkey BE (2003). Fatty acid metabolism and insulin secretion in pancreatic beta cells. Diabetologia 46, 1297–1312.[CrossRef][Medline]
Zinman B, Ruderman N, Campaigne BN, Devlin JT & Schneider SH (2003). Physical activity/exercise and diabetes mellitus. Diabetes Care 26, 73–77.
|
Acknowledgements |
|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
C; b 