Introduction: Genetic studies have supported the importance of hepatic glucose release in hyperglycemia among individuals with type 2 diabetes. This study investigated the effect of 6 weeks of resistance training on hepatocytes genes PGC1α and HNF4α expression as well as fasting glucose levels in rats with type 2 diabetes (T2D). Methods: This experimental study involved 21 male Wistar rats made obese by a 6-week high-fat diet. Subsequently, T2D was induced in 14 rats through STZ administration via intraperitoneal injection. Finally, the observed rats were divided into 3 groups (n=7): 1) non-diabetes, 2) diabetic control, 3) resistant to diabetic. The rats in the resistance group were completed resistance training for six weeks (5 times a week) by climbing a ladder while applying resistance. The control obese and control T2D groups did not participate in the resistance training. Forty-eight hours following the prolonged exercise session, hepatocytes genes PGC1α and HNF4α expression, along with serum insulin, glucose, and insulin resistance, was analyzed using One-Way ANOVA and Tukey post hoc test across different groups. Results: T2D induction led to significant decrease in insulin levels and an increase in fasting glucose, alongside increased insulin resistance and hepatocytes genes PGC1α and HNF4α expression when compared to non-diabetes rats. Resistance training resulted in a significant increase in serum insulin (p = 0.043) and a decrease in fasting glucose (p = 0.001), insulin resistance (p = 0.001) and hepatocytes HNF4α expression (p = 0.001), compared to the control diabetic group. Conclusion: Six weeks of resistance training resulted in a reduction in fasting glucose, and this improvement may be linked to a decrease in HNF4α expression and insulin resistance resulting from the resistance training.

Objective: Genetic studies indicate that available insulin influences the activity or expression of hepatic gluconeogenic genes. This study aimed to assess the effect of resistance exercise program on gluconeogenic genes expression and their change relation with insulin in response to training. Materials and Methods: 18 male wistar rats by 6 weeks high-fat diet were studied. Type 2 diabetes was induced by intraperitoneal injection of STZ (25 mg/dl) in 14 rats. Finally, the studied rats were selected into 3 groups: 1) non-diabetic, 2) control diabetic, 3) resistance diabetic. Rats in the resistance group participated in a 6-week resistance training in the form of climbing a step ladder with resistance and other groups remained none-training. ANOVA statistical test used to compare glucose, insulin and hepatic expression of PEPCK, G6Pase and HNF4α between groups. Correlation between insulin changes and gene expression was determined by Spearman's correlation test. Results: Serum insulin significantly increased following resistance training intervention (P= 0.043). A significant decrease was also observed in fasting glucose (P= 0.001) and hepatic expression of PEPCK (P= 0.001), G6Pase (P= 0.001) and HNF4α (P= 0.011) compared to control diabetes rats. Significant inverse correlation was observed in the change of insulin with HNF4α (P= 0.001), PEPCK (P= 0.013) and G6Pase (P= 0.043) in response to resistance training. Conclusion: Resistance training is associated with changes in the expression of gluconeogenic genes, and these changes can probably be attributed to changes in serum insulin.

Objective: Hepatic glucose release is greatly increased in the presence of obesity and related diseases. The research objective was to explore the impact of high intensity interval training (HIIT) on TCF7L2 gene expression in hepatocytes of obese rats. Materials and Methods: Out of 21 male Wistar rats aged 10 weeks years (220±10 g), obesity was induced in 14 rats by 8-week high-fat diet. The rats were then divided into normal (n=7), obese control (n=7), and HIIT obese (n=7) groups. Rats in the HIIT group completed 8 weeks of HIIT/5 days weekly, whereas the other groups were inactive. After intervention, TCF7L2 gene expression in hepatocytes, insulin resistance and glucose compared using ANOVA /Tukey’s post hoc test between groups by SPSS-22. Results: Obesity induction led to a significant decrease in TCF7L2 gene expression (P: 0.011) and an increase in blood glucose (P: 0.009) and insulin resistance (P: 0.019) compared with the normal group (P< 0.001). On the other hand, interval training led to a significant increase in TCF7L2 gene expression (P: 0.029) and a decrease in blood glucose (P< 0.001) and insulin resistance (P< 0.001) in the obese group compared with the control group. Conclusion: The observed enhancement in fasting blood glucose levels among obese rats could be linked to increased TCF7L2 gene expression in liver cells, which appears to be a response to interval training intervention. Nevertheless, understanding the main mechanisms responsible for observed changes requires further studies in this field.

Introduction: IGF-1 is a polypeptide hormone that plays a vital role in the development and regeneration of skeletal muscles. IGF-1 activates anabolic pathways such as PI3K and IRS-1/2 to activate a series of intracellular anabolic signals. The purpose of this study was to investigate the effect of 8 weeks resistance training on IGF1, PI3K and insulin sensitivity in neural muscle in type 2 diabetic rats. Methods: In this experimental study, 14 male Wistar mice aged 8 to 10 weeks and induction of type 2 diabetes (type 2 diabetes was induced by intraperitoneal injection of nicotinamide and STZ in diabetic groups) and were divided into two groups of resistance training and control groups. The mice in the control group did not exercise during the study, while the resistance group performed 8 weeks of training for 5 sessions per week. Resistance exercises in each session were performed in the form of 10 repetitions with 90-second rest intervals in the form of climbing a 26-step ladder to a height of one meter with a vertical slope of 85%, and weight was applied to the base of the rat's tail. 48 hours after the last training session, blood samples were taken from the heart and neural muscle tissue was extracted. Real Time-PCR method was used to determine the genes and one-way ANOVA test was used to compare the variables. All statistical studies were done using SPSS version 16 software. Results: The results of this study showed that expression of IGF-1 and PI3K in the duodenal axis of diabetic rats in resistance training group was significantly higher than that of the control group (P = 0.001) (P = 0.11). Serum insulin sensitivity in diabetic rats was not significantly different in diabetic rats compared to the diabetic rats (P=0.778). Conclusion: It seems that eight weeks of resistance training can be a strong stimulus on IGF-1 and PI3K gene expression and no change in insulin sensitivity in neural muscle in type 2 diabetic rats.

Objective: Overweight and obesity is associated with insulin resistance and is the most important risk factor of type 2 diabetes (T2DM). In present study, we assessed glycemic profile and insulin resistance response to a short term aerobic training in middle-aged men with abdominal obesity. Materials and Methods: The subjects included 28 abdominally obese (waist circumference≥102cm) middle-aged men (39 ± 5 year) that were divided into exercise (n=14) or control (n=14) groups by randomly. Exercise subject were completed a short-term aerobic training at 55-70 % of maximal heart rate (6 weeks, 3 times / weekly) and control subjects remained no training. Pre-training and post-training of anthropometrical markers, fasting glucose, hemoglobin (HbA1C), insulin and insulin resistance were measured of 2 groups and compared by independent – paired t test (SPSS, Version 22.0). Results: Aerobic exercise resulted in a significant decrease in glucose level (114 ± 13 versus 101 ± 11 mg/dL, P: 0.009) and HbA1C (6.14 ± 1.11 versus 4.91 ± 1.23, P: 0.021) in exercise group. But no significant changes were observed in insulin (8.31 ± 4.12 versus 8.29 ± 3.21, P: 0.119) and insulin resistance (2.34 ± 0.51 versus 2.07 ± 0.59, P: 0.073) in exercise groups. Conclusion: Based on our finding, aerobic training independent of insulin function is associated with improved glucose in middle-aged obese men and this improvement can be attributed to other changes caused by exercise that requires further study in this area.

Background and objectives: Genetic studies have indicated the effective role of transcription factors in insulin synthesis and secretion, especially in the case of diabetes. This study aimed to assess the effects of high-intensity interval training on transcription factor 7-like 2/ glucagon-like peptide 1 (TCF7L2 / GLP-1) axis in pancreatic tissue of obese rats with type 2 diabetes mellitus (T2DM). Methods: For this purpose, obesity was induced in 21 male Wistar rats (weighting 220±10 g) by exposure to a high-fat diet for six weeks. Then, the rats were randomly assigned to a non-diabetic, a control T2DM, and an exercise diabetic group. Next, T2DM was induced by intraperitoneal injection of streptozotocin (25 mg/kg). The rats in the exercise group participated in a HIIT program, five times a week, for six weeks. After the intervention, TCF7L2 and GLP1 expression in the pancreas tissue was determined by real-time PCR. Serum insulin, glucose, and beta cell function were compared between the study groups. Data were analyzed using one-way ANOVA and Tukey post hoc test at a significance level of 0.05. Results: Induction of T2DM increased glucose level and TCF7L2 expression but decreased insulin, beta cell function, and GLP-1R expression. In addition, HIIT significantly decreased TCF7L2 expression as well as glucose level, serum insulin, and beta cell function; however, it did not significantly change GLP-1R expression compared with the control diabetes rats. Conclusion: Based on the findings, the improvement of serum insulin and glucose level following HIIT may be attributed to the decrease in TCF7L2 gene expression in the pancreatic tissue of diabetic rats.

Objective: Apart from hormonal factors and oxidative stress, insulin synthesis is strongly dependent on transcription factors in the pancreas. The aim of the present study was to assess the impact of high-intensity interval training (HIIT) on genes affecting insulin synthesis in diabetic obese rats. Materials and Methods: Type 2 diabetes (T2D) was induced by a 6-week high-fat diet (HFD) and intraperitoneal injection of streptozotocin (25 mg /kg) in 14 male Wistar rats (10 week old, 220±10 g). Rats with fasting glucose levels between 400 and 150 were considered T2D. The diabetic rats were randomly assigned to exercise (HIIT: 6 weeks/5 sessions weekly, n= 7) or control (n= 7) groups. Forty-eight hours after the intervention, fasting GLP-1R and PKBα gene expression in pancreatic tissue and plasma insulin and glucose levels were compared between the groups. Data were compared by independent t-test used to compare variables, version 22 between groups. A P< 0.05 was considered significant. Results: HIIT led to significant increase in PKBα gene expression (P: 0.001) and insulin (P: 0.031) and decreases in glucose concentration (P: 0.001) compared with the control group. No change was observed in the GLP-1R gene expression response to HIIT (P: 0.093). Conclusion: HIIT is associated with increased serum insulin levels in T2D obese rats. Despite no change in GLP-1R, this improvement is probably rooted in increased expression PKBα in pancreas in response to this type of exercise training.

Background and objectives: Clinical evidence has demonstrated the important role of adiponectin in insulin signaling pathways in target tissue. The aim of this study was to determine effects of aerobic training on insulin sensitivity, glucose level, and adiponectin expression in subcutaneous adipose tissue of type 2 diabetic rats. Methods: Type 2 diabetes was induced in 14 male wistar rats by intraperitoneal injection of nicotine amide and streptozotocin. The rats were randomly divided into an exercise group (n=7) and a control group (n=7). The rats in the exercise group performed aerobic training in from of treadmill running, five sessions a week, for 12 weeks. Subjects in the control group did not perform any training. Glucose level, insulin level, insulin sensitivity, and adiponectin expression in subcutaneous adipose tissue were determined at baseline and 48 hours after the lasting training session. Independent t-test was used for comparing the variables between the study groups. Results: Aerobic training resulted in a significant increase in serum insulin (p=0.006), insulin sensitivity (p=0.003), and adiponectin expression in subcutaneous adipose tissue (p=0.037) compared with the control group. In addition, the training caused a significant decrease in fasting glucose level compared with the control group (p<0.001). Conclusion: Based on these findings, the decrease in blood glucose may be attributed to the improvement of adiponectin-dependent insulin signaling pathways in adipose tissue in response to aerobic training. However, more cellular-molecular studies are needed to understand the mechanisms responsible for these changes.

Objective: Forkhead box proteins and Forkhead box transcription factor O1 (FOXO1) in particular, mediate insulin signaling pathways and glucose homeostasis. This study aimed to compare FOXO1 expression in subcutaneous adipose (SA) tissue between obese rats with and without type 2 diabetes (T2D) and its response to resistance training in T2D. Materials and Methods: 21 male wistar rats (220±20 g) were obese by 6 weeks high fat diet (HFD) and randomly assigned to either non-diabetes (n=7) or two T2D groups (control and exercise groups, n=7 in each case). Fasting glucose, insulin, insulin resistance and FOXO1 expression were compared between non-diabetes and diabetes groups. All variables were also assigned after resistance training in the form of climbing a ladder (6 weeks/5 times weekly) in exercise compare with control groups. Data were compared by ANOVA, independent and paired t-test methods (P<0.05). Results: Induction of diabetes resulted in significant increase in insulin resistance, glucose, and FOXO expression in SA tissue and a decrease in insulin compared to obese health rats (P< 0.0001). A significant decrease in fasting insulin (P< 0.0001), insulin resistance (P< 0.0001) and FOXO1 expression in SA tissue (P< 0.0001) and increase in insulin (P: 0.002) were observed by resistance training compared to control diabetes rats. Conclusion: Based on our results, improving insulin resistance and glucose in response to resistance training in obese diabetic rats may be rooted in decreased insulin expression following these exercises.

Background: The potential role of exercise in physiological cardiac hypertrophy is rooted in both hormonal and genetic components. Objectives: The aim of this study was to determine the impact of resistance exercise on the expression of PI3K and AKT1 in cardiac tissue of type 2 diabetes (T2D) rats and their physiological cardiac hypertrophy. Methods: First, 21 male Wistar rats (220±20 g) were obese with 6-week high-fat diet (HFD) and were randomly assigned into non-diabetes, control T2D, and exercise diabetes groups. After inducing obesity, T2D was induced by intraperitoneal injection of streptozotocin (25 mg/kg) for diabetes groups. Rats in the exercise group completed a 6-week resistance exercise program, 5 sessions per week. PI3K/AKT1 expression and the weight ratio of left ventricular to heart, heart to body, and left ventricular to body were compared by analysis of variance (ANOVA) between groups. Results: In response to the induction of diabetes, the expression of PI3K/AKT1 in heart tissue decreased significantly compared to that of non-diabetic rats (P=0.001 and P=0.001, respectively). Further, resistance training led to a significant increase in PI3K expression (P=0.028) and AKT1 (P=0.032) and the weight ratio of left ventricular to heart (P=0.001), heart to the body (P=0.001), and left ventricular to the body (P=0.001) compared to control diabetic rats. Conclusion: Resistance training is associated with physiological cardiac hypertrophy in diabetic rats, and this improvement may be attributed to the PI3K/AKT1 signaling pathway.

Background: Clinical evidence supports the influential role of genetic factors and intracellular signaling pathways in physiological cardiac hypertrophy. This study aimed to assess the response of the PI3K/mTORc1 signaling pathway in cardiac tissue to resistance training in obese rats with Type 2 Diabetes (T2D). Materials and Methods: A total of 21 male Wistar rats (Mean±SD weight: 220±20 g) were obese by 6 weeks High-Fat Diet (HFD) and randomly assigned to 1) non-diabetic, 2) control T2D, and 3) exercise diabetic groups. T2D was induced by intraperitoneal injection of streptozotocin (30 mg/kg) for diabetic groups. The exercise group did the resistance exercise program (5 times per week for 6 weeks). After exercise training, PI3K and mTORc1 expression in the left ventricle and the ratio of the left ventricle to heart and heart to body weight were compared between groups. The obtained data were compared by 1-way Analysis of Variance (ANOVA) (P<0.05). Results: Induction of diabetes resulted in significant decrease in all mentioned variables in control diabetic to non-diabetic rats (PI3K; P=0.021, mTORc1; P=0.004, left ventricle/heart weight; P=0.045, heart/body weight; P=0.035). Significant increase was observed in all variables (PI3K; P=0.028, mTORc1; P=0.015, left ventricular/heart weight; P=0.002, heart/body weight; P=0.001) in response to resistance training compared to the control rat. Conclusion: Based on our results, cardiac hypertrophy in studied diabetic rats can be attributed to improved PI3K/mTORc1 signaling in response to resistance training. Exploring the exact mechanisms responsible for these changes in response to exercise requires further molecular-cellular studies.

Objective: Obesity is associated with inflammatory process and many different diseases. The objective of this study was to assess the impact of short term aerobic training on serum resistin and insulin resistance in adult obese women. Materials and Methods: In this quasi-experimental study, thirty untrained adult obese females matched for age 35-45 years old with body mass index (BMI) 30-36 kg/m2 were divided randomly into exercise (aerobic intervention; 6 weeks, 3 days/weekly, %55-70HRmax) and control (no training) groups. Pre and post-training of fasting blood samples were collected for measure serum resistin. Insulin resistance was calculated by HOMA-IR. Data were analyzed by the independent samples T-test. Results: Aerobic training resulted in significant decrease in BMI (32.1 (± 2.76) vs 31.6 (± 2.80) kg/m2, P-value: 0.023), body fat percentage (44.7 (± 4.55) vs 44 (± 4.33), P-value: 0.028) and fasting glucose (94 (± 8.9) vs 79 (± 5.8) mg/dl, P-value: 0.011) in exercise group. No changes were observed on insulin resistance (1.43 (± 1.11) vs 1.18 (± 0.57) HOMA-IR, P-value: 0.124) and serum resistin (2.20 (± 1.07) vs 1.58 (± 0.87) ng/ml P-value: 0.062) by training program. All variables remained unchanged in control subjects. Conclusion: Despite improving fasting glucose, a short-term aerobic training is not associated with anti-inflammatory property for obese females. Improved glucose could be likely attributed to other changes in metabolic markers in response to exercise training and further studies are necessary to clarify possible mechanisms

Background and Aim: Regular exercise training is the principal non-pharmacological method for the prevention and treatment of metabolic syndrome or other obesity-related diseases. We investigated the effects of aerobic training on leptin and cardiovascular risk factors in middle-aged men with metabolic syndrome. Methods: Twenty-six sedentary middle-aged males with metabolic syndrome aged 40 ± 5 years were randomly assigned to two groups as exercise (aerobic training, n =13) and control (no training, n =13). The exercise programs were performed 3 days a week for 10 weeks at 55-75% of HRmax. Fasting blood samples were taken before and after the training period for measuring serum leptin and triglyceride (TG), total cholesterol (TC), LDL, and HDL as cardiovascular risk factors. Results: No significant differences were observed between groups concerning anthropometric and clinical markers at baseline (p>0.05). Aerobic intervention resulted in significant decrease in anthropometric markers (abdominal circumference, body mass index, body fat percentage; p < 0.05), serum leptin (p = 0.026), TG (p = 0.001) and HDL (p = 0.032) in exercise group, but significant changes were not found in TC (p = 0.522) and LDL (p = 0.546). There were no changes in all measured variables in the control group. Conclusion: Based on our finding, it seems that regular aerobic exercise is associated with improved serum leptin and cardiovascular function in patients with metabolic syndrome. *Corresponding Author: Mojtaba Eizadi; Email: izadimojtaba2006@yahoo.com Please cite this article as: Naseri Rad R, Eizadi M. Regular Exercise Training as a Principal Non-Pharmacological Method Affects Serum Leptin and Cardiovascular Risk Factors in Men with Metabolic Syndrome. Arch Med Lab Sci. 2020;6:1-8 (e1). https://doi.org/10.22037/amls.v6.31643

Background and Objective: Hormone and genetic disorders are the most important causes of hyperglycemia in obese and diabetes patients. This study was done to determine the effect of the resistance training program on FOXO1 gene expression in subcutaneous adipose tissue as an effective transcription factor in insulin signaling pathways, fasting glucose and insulin resistance in type 2 diabetic rats. Methods: In this experimental study, type 2 diabetes induced by high fat diet and Streptozotocin (STZ, 30 mg/kg/bw) intraperitoneal injection in 14 male wistar rats (220±20 g) .Animals were randomly allocated into exercise (n=7) and control (n=7) groups. Exercise group were participated in resistance training program (6 weeks, 5 days/weekly). Fasting blood glucose and insulin as well FOXO1 gene expression in subcutaneous adipose tissue were measured lasted exercise session in the two geoups. Results: Resistance training significantly reduces in fasting glucose, insulin resistance and FOXO1 gene expression in subcutaneous adipose tissue in exercise group in compared to control group (P<0.05). Conclusion: Resistance training lead to decrease of insulin resistance and blood glucose by inhibiting FOXO1 gene expression in subcutaneous adipose tissue in diabetic rats.

Introduction: Obesity is a major risk factor for inflammation and cardiovascular diseases. We tried to assess whether 12 weeks of aerobic exercises affect serum resistin level and lipid profile in overweight females or not. Methods: For this purpose, 32 non-trained adult females with the mean age of 38 ± 7 years old and body mass index (BMI) of 32 ± 3 kg/m2 were randomly assigned to aerobic exercise (n=16) and control (n=16) groups. Twelve weeks of aerobic exercise program including 3 sessions weekly at 60-75% of maximum heart rate was considered. Fasting serum resistin level, lipid profile (total cholesterol [TC], low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglyceride [TG]), and anthropometric indexes were measured and compared between the two groups before and after training. Results: Serum resistin, lipid profile markers, and anthropometrical indexes were not significantly different at baseline between the two groups (P>0.05). TG, TC, LDL, and serum resistin did not change significantly after the intervention in the exercise group (P>0.05). However, a significant increase in HDL (exercise: 46.3 ± 9.6 vs. 51.4 ± 8.5, P=0.011; control: 45.8 ± 7.9 vs. 46.8 ± 6.9 P=0.326) and a significant decrease in LDL/HDL ratio (exercise: 2.94 ± 0.12 vs. 2.47 ± 0.19, P=0.019; control: 3.14 ± 0.23 vs. 3.18 ± 0.63, P=0.265) were observed after the intervention. Other variables in the control group remained unchanged. Conclusion: Aerobic exercises had no impacts on the inflammatory profile but could improve lipid profile with an emphasis on HDL in adult obese women.