Effect of Oxytocin Treatment on Asprosin Serum Level and Liver Function Changes in Rats with Streptozotocin-Induced Diabetes

Abstract
Background: Asprosin is a newly discovered hormone that was found to be increased in cases of type 2 diabetes mellitus but, few data were available on its serum level changes in cases of streptozotocin (STZ) induced diabetes. Also, studies on the effect of STZ induced diabetes on liver functions were limited. In addition, exogenous oxytocin treatment was re-corded to improve glucose homeostasis in cases of type 2 diabetes mellitus and insulin resistance, but, the information about its effect on STZ induced diabetes was few.
Aim of Study: To investigate the effect of exogenous oxytocin treatment on asprosin serum level and liver function changes in rats with STZ-induced diabetes.
Material and Methods: 24 Rats were divided equally into 4 groups; control group, streptozotocin treated (STZ) group, streptozotocin treated and pretreated with oxytocin (pre-STZ) group, and, streptozotocin treated and post-treated with oxy-tocin (post-STZ) group. In the control group, 1ml of saline solution was daily injected intraperitoneally (i.p.) for the 1st 6 days and the last 5 days of this 39 days study. In STZ group, a single dose of STZ (60mg/kg, freshly dissolved in 1 ml of saline solution) was injected i.p. on the 6th day after initial 1ml of saline solution was daily injected i.p. for the 1st 5 days. Also, 1ml saline/day was injected i.p. in the last 5 days of the study. In Pre-STZ group, 5mg/kg of oxytocin was daily injected i.p. for 5 days prior to the administration of a single dose of STZ injection and in the last 5 days of the study, 1ml of saline was injected i.p. daily. In post-STZ group, 5m  g/kg of oxytocin was daily injected i.p. for 5 days beginning by 28th day following the administration of single dose of STZ injection on the 5th day which was preceded by 5 days i.p. therapy with 1ml of saline/day. At the end of the study, rats were fasted overnight and were killed by decapitation while anaesthetized with ether. Blood from each rat was collected and divided into two parts, a part was kept in heparinized tubes for estimation of glycosylated hemoglobin (HbA 1 c) and the other part was left in non-heparinized tubes to clot and was centrifuged to separate serum which was stored at - 25ºC till used for chemical assays.
Results: In STZ group, there was a significant (p<0.001) increase in serum levels of glucose, total cholesterol (TC),
triglycerides (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), tumor necrosis factor alpha (TNFa), % HbA1c and atherogenic index, but, there was a significant (p<0.001) decrease in final body mass index (BMI) and serum levels of each of insulin, C-peptide and high density lipoprotein (HDL), in comparison to the control group. Also, serum asprosin level was significantly (p<0.001) reduced in STZ group in comparison to the control. Moreover, significant (p<0.001) increases in serum levels of aspartate aminotrans-ferase (AST), alanine aminotransferase (ALT), alkaline phos-phatase (ALP) and total bilirubin, but, significant (p<0.001) decreases in serum direct bilirubin, total protein and albumin levels were found. Furthermore, there were positive associa-tions between serum asprosin and each of final BMI (r=0.948, p<0.01), serum insulin (r=0.946, p<0.01), serum C-peptide (r=0.85, p<0.05), serum HDL (r=0.936, p<0.01), serum direct bilirubin (r=0.902, p<0.05), serum total protein (r=0.867, p<0.05) and serum albumin (r=0.942, p<0.01), but, negative correlations between serum asprosin and each of serum glucose (r=–0.979, p<0.001), serum TC (r=–0.966, p<0.01), serum TG (r=–0.969, p<0.01), serum LDL (r=–0.942, p<0.01), serum VLDL (r=–0.858, p<0.05), % HbA1c (r=–0.918, p<0.01), serum TNF± (r=-0.96, p<0.01), atherogenic index (r=–0.97, p<0.01), serum AST (r=–0.977, p<0.001), serum ALT (r=–0.952, p<0.01), serum ALP (r=-0.958, p<0.01) and serum total bilirubin (r=–0.925, p<0.01). On the other hand, in pre-STZ group a significant (p<0.001) decrease in serum levels of glucose, TC, TG, LDL, VLDL, TNFa, % HbA1c and atherogenic index, but, there was a significant increase in final BMI (p<0.01) and serum levels (p<0.001) of each of insulin, asprosin, C-peptide and HDL, in comparison to the STZ group was found. Also, significant (p<0.001) decreases in serum levels of AST, ALT, ALP and total bilirubin, but, significant (p<0.001) increases in serum direct bilirubin, total protein and albumin levels in comparison to the STZ group were found. In post-STZ group, there was a significant (p<0.001) decrease in serum levels of glucose, TC, TG, LDL, VLDL, TNFa, % HbA1c and atherogenic index, but, a signif-icant increase (p<0.001) in serum levels of insulin, asprosin, C-peptide and HDL, in comparison to the STZ group. Also, significant (p<0.001) decreases in serum levels of AST, ALT, ALP and total bilirubin, but, significant (p<0.001) increases in serum direct bilirubin, total protein and albumin levels were found in comparison to the STZ group.
Conclusion: Asprosin levels were significantly decreased in cases of STZ induced diabetes in comparison with the control, but, increased with oxytocin treatment whether before or after STZ treatment in comparison with STZ group. Also, in STZ group, asprosin was positively correlated with final BMI, serum insulin, serum HDL, serum direct bilirubin, total protein and albumin, but, negatively associated with serum glucose, TC, TG, LDL, VLDL, TNF х, AST, ALT, ALP, total bilirubin, HbA1c and atherogenic index. Thus, changes in circulating asprosin affected glucose homeostasis and subse-quently the pathogenesis and complications of diabetes mellitus and might be a predictor of early diagnosis in diabetes mellitus. Also, in STZ group, liver functions were affected in the form of a significant increase in liver enzymes and total bilirubin but, a significant decrease in direct bilirubin, total protein and albumin. Oxytocin treatment pre or post STZ treatment protected or restored the functional ß-cells, and, improved lipid profile and liver functions.