HISTOLOGICAL EFFECTS OF CREATINE SUPPLEMENTATION IN RATS WITH DIABETES INDUCED BY STREPTOZOTOCIN
Diabetes mellitus, creatine, pancreas, kidney
Diabetes Mellitus (DM) is a chronic metabolic disease that is growing all over the world and is characterized by a hyperglycemic condition due to a reduction in circulating insulin levels and/or a deficit in the tissue effects of this hormone. In 2019, the estimated number of carriers was 463 million and the projection is that it will reach 578 million in 2030, and 700 million in 2045. Type I DM, the pathological condition targeted by the study, is associated with acute metabolic complications as well as chronic complications of long term, having the following organs and structures most affected: pancreas, kidneys, nerves, heart, blood vessels, retina and lung. Research is constantly carried out in an attempt to alleviate these complications and, therefore, improve the quality of life of patients. For this, studies are carried out with adjuvant therapies. Nutritional supplements demand a lot of attention to comply with this practice. Creatine is a nutritional supplement that has been studied due to its antioxidant and hypoglycemic features. Studies in type II DM are already increasing the effect of creatine in increasing glucose uptake and increasing insulin sensitivity, however, there are no studies on this effect of supplementation both on metabolism and, especially, on tissues that can be affected in the Type I DM. Thus, this study aimed to evaluate the effects of creatine supplementation in diabetic rats induced by streptozotocin (STZ). For this, 32 Wistar rats were used, divided into 4 groups containing 8 animals each: (C) animals without diabetes and without creatine supplementation, (CCr) animals without diabetes and with creatine supplementation, (D) induced diabetic animals with STZ without supplementation, (DCr) diabetic animals induced with STZ treated with creatine. Groups D and DCr received a single dose of STZ (40 mg/kg i.p.) for diabetes induction. The CCr and DCr groups received creatine supplementation through an isocaloric diet in 2 phases (saturation and maintenance). After euthanasia, organs were collected and stored for histopathological analysis of the animals' pancreatic and renal tissues. In order to prove the DM induction for groups D and DCr, the consumption of water and feed was measured, as well as the body weight to characterize the symptoms of the pathological condition. In addition to hyperglycemia throughout the experiment, polydipsia, polyphagia and decreased body weight were observed in STZ-induced diabetic animals. Creatine supplementation was able to lower blood glucose, as seen in previous studies. In the pancreatic tissue, a decreased decrease in the number of islets of Langerhans in group D was observed in relation to the control groups, which corroborates the effect of STZ responsible for the destruction of beta cells and, consequently, an atrophy of the islets. The DCr group had the quantity of islets similar to that observed in the animals in the control group. This same group again presented an increase in relation to group D, regarding an area of the islets, corroborating the increase, in mm², which approximates the findings for the control groups. As in the pancreas, the renal glomerulus count was performed. There is a reduced reduction in the amount of the DCr group compared to the other experimental groups. The creatine transporter present in the rim may favor some tissue damage, related to the release of its NO group. It may also be related to glomerular findings present in the histology of this group, which can destroy this structure. As for glomerular areas, the DCr group was similar to the control groups, while the D group presented smaller areas of the renal glomeruli. This may reflect in the DCr group a compensatory increase in mesangial expansion to preserve a filtration surface, while for the D, a glomerular atrophy due to fibrosis (hyalinization). It is common to find in morphological and histological research a pattern of needs when researching DM. Therefore, creatine supplementation in diabetic animals was effective in terms of pancreatic and renal morphometric analyzes as well as some histological parameters adopted, drawing attention to adipose replacement and hyperemia for the pancreas and renal glomerulosclerosis, and improvement in inflammation and necrosis for the bones two tissues from the study. However, of course, further investigations are needed to increase the evidence of this supplementation with type I DM, including histological analyzes and specific metabolic markers since tissue alterations can develop in complete clinical silence. As well as analysis of the expression of genes that influence tissue damage and transporters that can also influence some injury.