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Continuous and Intermittent Exercise Training and Glucose Metabolism in Neonatal Alloxan Administered Rats

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Continuous and Intermittent Exercise Training and Glucose Metabolism in Neonatal Alloxan Administered Rats Elmer Press Original Article J Endocrinol Metab • 2011;1(3):101-112 Continuous and Intermittent Exercise Training and Glucose Metabolism in Neonatal Alloxan Administered Rats Carla Ribeiroa, b, Lucieli Teresa Cambria, Rodrigo Augusto Daliaa, Michel Barbosa de Araujoa, Jose Alexandre Curiacos de Almeida Lemea, Rodrigo Ferreira de Mouraa, Fabricio Azevedo Voltarellia, Maria Alice Rostom de Melloa Abstract Keywords: Neonatal rats; Alloxan; T2DM; Exercise training; Glu- cose uptake Background: This study aimed to compare the effects of intermit- tent and continuous swimming training on glucose metabolism in neonatal alloxan treated rats. Introduction Methods: Alloxan was injected in newborn rats at 6 days of age (250 mg/kg bw). At 28 days of age, the animals were divided into In recent years, the incidence of type 2 diabetes mellitus sedentary alloxan (SA), sedentary control (SC), continuous trained (T2DM) has considerably increased [1, 2]. T2DM is char- alloxan (CA), intermittent trained alloxan (IA), continuous trained acterized by insulin resistance, which leads to characteris- control (CC) and intermittent trained control (IC) groups. The con- tic hyperglycemia [2, 3]. This form of diabetes accounts for tinuous training protocol consisted of 12 weeks swimming (1 h/ day), uninterrupted, fi ve days a week, in individual cylinder tanks 90-95% of diabetes and can be triggered by various factors (25 cm diameter x 50 cm depth), and with supporting overload of such as obesity, high calorie diet and physical inactivity [2, 5% bw. Intermittent training consisted of 12 weeks of swimming 4]. On the one hand, regular physical exercise, particularly (30 s), interrupted by rest (30 s), in individual cylinder tanks (25 cm in the treatment of this disease, improves glucose tolerance diameter x 50 cm depth), for a total of 20 min/day, fi ve days a week, and improves insulin responsiveness [5-8]. The possible and with an overload of 15% bw. mechanisms by which exercise induces benefi cial changes in insulin sensitivity include the development of muscle mass, Results: At 28 days, the alloxan treated animals showed both a increases in the peripheral glucose uptake and the reduction higher area under the curve (AUC) values for serum glucose during in the amount of insulin required for maintaining glucose ho- a glucose tolerance test (GTT) and a lower glucose disappearance meostasis [9-11]. However, the discussion continues about rate (Kitt) during an insulin tolerance test (ITT), indicating insu- the intensity of the effort, the training protocol and the peri- lin resistance in the fi rst group. At 120 days, the alloxan treated animals subjected to the intermittent training showed higher serum odicity to be prescribed for T2DM patients. glucose AUC than the controls after a GTT. The glucose uptake Unfortunately, there is a lack of direct evidence in the by isolated soleus muscle was higher in the animals trained by the literature for the preventative effect of exercise on the devel- intermittent protocol than in the others. opment of T2DM, because this type of study is diffi cult to implement in human subjects. In this context, animal models Conclusions: In conclusion, intermittent exercise was more ef- provide more suitable conditions to study the issue. Chemi- fective than continuous exercise in improving glucose uptake by cally induced diabetic animals have been widely used as an skeletal muscle. experimental model for studies of the complications caused by diabetes [12] and the effects of physical exercises. Portha et al. [13] described an experimental model of neonatal diabetes in Wistar rats, by application of strepto- zotocin on the day of birth. In this model, it was demonstrat- Manuscript accepted for publication August 1 2011 ed that hyperglycemia is transitory. The blood glucose levels aDepartment of Physical Education, Sao Paulo State University return to normal after the fi rst week of life, with restoration (UNESP), Rio Claro-SP, Brazil of insulin production and β-cell mass. It features a T2DM bCorresponding author: Avenue. 24 A, 1515, Bela Vista, Rio Claro-SP, model in rats, in which the experimental animals present CEP 13506-900, Brazil. Email: [email protected] good survival [13]. doi:10.4021/jem32w Later, Kodama et al. [14] developed another model, re- placing streptozotocin with alloxan. In this study, alloxan Articles © The authors | Journal compilation © J Endocrinol Metab and Elmer Press™ | www.jofem.org 101 Ribeiro et al J Endocrinol Metab • 2011;1(3):101-112 was administered at 2, 4 or 6 days of life. When analyzed In summary, both continuous training and intermittent at 60 days of life, rats that received alloxan on the second training seem to play important roles in the prevention and day of life showed slightly higher blood glucose compared treatment of type 2 diabetes mellitus, but further studies are to controls in the fed state. Animals that received the drug on needed to characterize the intensity and frequency best suit- the fourth and sixth days of life showed signifi cantly higher ed for each of these protocols. Thus, this study aims to com- blood glucose than controls. pare the effects of intermittent and continuous swimming The authors considered this a useful model for studies training, with equivalent loads, on the glucose metabolism in on chronic complications of diabetes, however, they empha- neonatal alloxan treated rats. sized that more studies were needed to determine whether it has T2DM characteristics, as seen in the neonatal strepto- zotocin model. Materials and Methods Oliveira et al. [15] examined the fasting plasma glucose and glucose tolerance in alloxan treated rats (day 2) of both Animals sexes at 30, 60, 90 days of age. Fasting glucose was not different from control rats at any Studies were carried out with newly born male Wistar rats, time. On the other hand, Contarteze et al. [16] showed that kept at 25 ± 1 ºC under a 12/12 h light-dark cycle and fed a these animals presented higher blood glucose concentrations standard rodent chow and water ad libitum. During breast- after an oral glucose load compared to controls. Ribeiro et feeding, food and water were offered ad libitum to the moth- al. [17], using rats that received alloxan at the 6th day of life, ers, and the pups were distributed in litters of eight per dam. also showed higher blood glucose values during a glucose Food and water intake and body weight were recorded week- tolerance test in the alloxan treated animals compared to the ly, after the weekend. All experiments using animals were control group, at both 28 and 60 days of age. Together, these approved by the committee of ethics in animal research, Tau- data show that the neonatal induction model of diabetes is bate University-CEEA/UNITAU, under protocol no. 019/08. an interesting model in which to study the role of exercise in preventing and treating this disease. Neonatal alloxan administration Studies using different training protocols in the prevention and treatment of type 2 diabetes mellitus are scarce and show At 6 days of age, male pups, with a body weight of 11.9 ± confl icting results. A study conducted with type 1 diabetics 1.2 g, received an alloxan monohydrate injection (Sigma-Al- (T1DM), which compared the effects of intermittent training drich Inc., St Louis, MO, USA), which was dissolved in ci- with high intensity of effort and continuous moderate training, trate buffer 0.01 M, pH 4.5 [22] and delivered intraperitone- showed that the reduction in blood glucose was less evident ally (250 mg/kg body weight) after a 15-h fast. Age-matched in the intermittent exercise group compared to the continuous controls were injected with vehicle alone (citrate buffer). moderate exercise group in individuals with T1DM [18]. Pups were immediately distributed in such a way that each Kuwajima et al. [19], using genetically modifi ed ani- mother nursed eight pups. mals (rats that develop obesity and glucose intolerance at 10 weeks of age), showed the prophylactic effect of continuous Experimental groups and design training in the development of T2DM. The cumulative inci- dence of T2DM in the sedentary group was 30, 67 and 78% At 28 days of age, the animals were randomly divided into at 10, 16 and 24 weeks of age, respectively. In the trained the following six groups and remained in observation until group, the T2DM incidence remained null throughout the 120 days of age (Fig. 1): experimental period. Control (C): citrate buffer-injected rats not subjected to Oliveira et al. [15] did not fi nd any changes in skeletal exercise training; muscle glucose uptake in rats subjected to neonatal applica- Continuous Training Control (CC): citrate buffer-inject- tion of alloxan after continuous swimming exercise of mod- ed rats subjected to continuous exercise training protocol; erate intensity. Mota el al. [20], using the experimental mod- Intermittent Training Control (IC): citrate buffer-inject- el of T2DM with neonatal administration of alloxan, showed ed rats subjected to intermittent exercise training protocol; improvement in glucose tolerance in diabetic animals after Alloxan (A): alloxan-injected rats not subjected to exer- 12 weeks of continuous swimming training, in the intensity cise training; of the maximal lactate steady state. Continuous Training Alloxan (CA): alloxan-injected In adult, diabetic rats induced by streptozotocin appli- rats subjected to continuous exercise training protocol; cation, continuous swimming exercise at different intensi- Intermittent Training Alloxan (IA): alloxan-injected rats ties, before and after the induction of diabetes, attenuated the subjected to intermittent exercise training protocol. hyperglycemia. The most pronounced effects were observed with the highest intensity of exercise [21]. Exercise training 102 Articles © The authors | Journal compilation © J Endocrinol Metab and Elmer Press™ | www.jofem.org Exercise Training and Glucose Metabolism J Endocrinol Metab • 2011;1(3):101-112 Figure 1.
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