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Journal of Diabetes and Metabolic Disorders logoLink to Journal of Diabetes and Metabolic Disorders
. 2019 Oct 10;18(2):379–387. doi: 10.1007/s40200-019-00422-1

Effects of moderate-intensity continuous training and high-intensity interval training on serum levels of Resistin, Chemerin and liver enzymes in Streptozotocin-Nicotinamide induced Type-2 diabetic rats

Parastesh Mohammad 1,✉, Khosravi Zadeh Esfandiar 2, Saremi Abbas 2, Rekabtalae Ahoora 1
PMCID: PMC6914745  PMID: 31890663

Abstract

Background

The aim of this study was to investigate the effects of of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) in serum resistin, chemerin, insulin, liver enzymes and lipid profiles levels.

Methods

24 Wistar rats with mean weight of 200 ± 50 g were randomly assigned to non-diabetic rats (ND-Cnt), diabetic control (D-Cnt), diabetic training groups. The diabetic training group received 10 weeks of HIIT (D-HIIT) and MICT (D-MICT) following the induction of diabetes. Evaluating resistin, chemerin and insulin hormones levels through ELISA. FBS and liver enzyme levels were measured by biochemical kits.

Results

HIIT and MICT resulted in a significant decrease in resistin, chemerin and fasting blood glucose (P < 0.05) compared to the D-Cnt (P < 0.05). Serum values of FBS, lipid profiles and liver enzyme (P < 0.05) decreased significantly more in the HIIT group compared with the MICT group (P < 0.05). As well as, the resistin level positively and significantly associated with values of ALT and chemerin level positively and significantly associated with values of ALT, ALP and AST in all rat (P < 0.05).

Conclusion

In general, our findings demonstrated that the HIIT leads to better improvements in serum liver enzyme levels, FBS and lipid profiles compared to MICT. HIIT therefore appears to be an important time-efficient treatment for treatment with type 2 diabetes rats.

Keywords: Diabetic, Resistin, Chemerin, Liver enzyme , Moderate-intensity continuous training (MICT), High-intensity interval training (HIIT)

Introduction

Diabetes mellitus (DM) is a chronic endocrine disease which accompanied with persistent (ongoing) hyperglycemia, and often resulting in absolute or partial deficiency of insulin secretion or insulin resistance [1]. Recent studies of the International Diabetes Federation have found in which worldwide equal to 382 million children and adults suffer from diabetes in 2013, and they predicted that global numbers of patients with diabetes reach more than 592 million until 2025 [2]. Too much evidence have stated on the role of oxidative stress and, consequently, the production of free radicals in the pathogenesis of diabetes and type of diabetes [3]. There are some disorders such as problems of eye, nerves, liver and blood vessels in diabetes which liver and kidney failures are known to be the most common causes of death in diabetic patients [4]. The liver is an effective organ in protecting the level of blood glucose in the normal range, and increasing the blood glucose leads to an imbalance of oxidation-reduction in reactions of liver cells [5]. Increases in hepatic enzymes of alanine aminotransferase (ALT), gamma -glutamyltransferase (GGT), Aspartate trans-aminase (AST), and alkaline phosphatase (ALP) have been suggested as predictors of diabetes [6]. Diabetes increases the level of hepatic enzymes in the blood, which is mainly due to increased oxidative stress in the tissue organs, and can also be partly due to an increase in blood glucose level [6]. Some studies have shown that plasma levels of liver enzymes are the best indicator for assessing of liver status due to increased levels of liver enzymes in blood under conditions of damage to liver cells [7]. On the other hand, resistin is one of the adipokine families which produced by adipose tissue, inflammatory cells such as macrophages and hepatic stellate cells [8]. In increasing the glucose secretion and insulin resistance of liver tissue conditions, it seems that liver is the main member of target for resistin and hyperresistinemia [9]. The treatment of healthy mice by resistin has caused disruption in glucose tolerance and insulin resistance induction, while injections of resistin antibodies in obese mice caused by a diet increase the insulin sensitivity [10]. Resistin is also expressed in liver while its production increases by increased liver damage [11]. This peptide reduces the expression of gluconeogenic liver enzymes; hence, after a fasting period, mice that do not have resistin show a lower glucose level due to liver glucose production [9]. On the one hand, although there are relations between resistin serum levels in streptozotocin-nicotinamide-induced diabetic mice, contradictory study indicate that serum resistin levels in these mice are more than those in the control treatment [12]. On the other hand, some of the other studies did not find the difference between resistin levels in diabetic and healthy mice [13]. In a research, Asalah et al. (2014) have observed that the hepatic enzymes such as ALT and AST were also increased after increasing the serum resistin levels in the obese rats with fatty liver [14]. Chemerin is another adipokine families that produced by liver and adipose tissue [15]. Hong et al. (2011) found that chemerin serum levels were increased in rates infected with metabolic syndrome cause to STZ and high-fat diets [16]. Chemerin binding chemokine-like receptor 1 (CMLKR-1) activates the cells of the innate immunity system e.g. macrophages and natural killer cells in damaged tissues [17]. On the other hand, liver hepatocytes are the main source of chemerin [18]. As well as, chemerin is in contact with the expression of CD68 cells [19] and liver expression of pro-inflammatory cytokines such as TNF-α, and it is participated in the production of inflammation [18]. Accordingly, the chemerin role in liver disorders of diabetic rats can be explained by close relationship of chemerin with inflammation. In support of these findings, it has been observed that there are positive and high correlations between serum chemerin levels, ALT and AST [14].

Physical activity can increase the response of skeletal muscle to insulin by increasing the expression or activity of proteins involved in the insulin metabolism and signaling, so that it increases physical activity of glycogen synthase activity and increases the expression of glucose transporter proteins. Physical activity in patients with diabetes is accompanied with reduction of fat oxidation and displacement towards more carbohydrate oxidation in all intensity sports. In diabetic patients with insulin deficiency, regular physical exercises can help facilitate the entry of sugar into muscle cells and, consequently, their consumption via increasing insulin sensitivity and in the absence of insulin. Also, sports activities with increased levels of glucose carrier proteins reduce insulin resistance [20]. On the other hand, in scientific studies, since the positive effects of continuous training with low to moderate intensity are undeniable, according to the results of new researches, it is now clear that High-Intensity Interval Training (HIITs) produce more favorable results in shorter time than the Moderate-Intensity Continuous Training (MICT) when are considered the overall health of the individual, the benefits, and shortage of time for individuals. In the research, Dendil et al. (2009) clearly showed that High-intensity interval training (HIIT) compared to Moderate-intensity continuous training (MICT) reduced the fast blood glucose and insulin levels and increased the insulin sensitivity in patients with type 2 diabetes [21]. It can also be stated that people who are going to participate in sports activities, because the high intensity interval training (HIITs) than the continuing exercises require less time to benefit Physical activity, they can’t excuse the lack of time to engage in these exercises [22]. In general, there are many contradictions in the results of the training methods, and, on the one hand, the mechanism of the useful effects of these training methods on the subject of the present study is not well understood. Therefore, in order to evaluate the use of different sports activities in preventing and improving the lateral complications of diabetes by controlling the related indicators, this study aimed to investigate the effects of moderate intensity continuous training (MICT) and high intensity interval training (HIIT) on serum resistin levels, chemerin and liver tissue damage indices in rats with type 2 diabetic.

Methods

Ethics statement and animal care

All protocols and animal care and handling described in the present study strictly followed the National Institutes of Health Guide for the Care and Use of Laboratory Animals. The code of ethics is also included in the description (IR.Arakmu.rec.1395.353) in the ethics committee of the research projects of Arak University of Medical Sciences. Male Wistar rats in the weight range of 200–250 g, were obtained from the Central Animal House, Tehran University of Medical Sciences, and were kept in cages under controlled humidity (60%) and temperature (25 °C) with a 12 h light/12 h dark cycle. All animals had free access to rodent maintenance chow and water ad libitum. All research and laboratory animal care processes were conducted according to the Guide for the Care and Use of Laboratory Animals (8th edition; National Academies Press; 2011) and approved Review Board and Ethics Committee of Arak University of Medical Sciences.

Diabetic induction

Diabetes was induced after a 12 h fast. The rats were injected with Nicotineamid (Sigma Chemical Co) dissolved in normal saline at a dose of 120 mg/kg, and after 15 min, streptozotocin (STZ, Sigma Chemical Co) dissolved in 0.1 M citrate buffer at a dose of 65 mg/kg was given in a single intraperitoneal injection. 72 h after injection, animals’ blood glucose levels were evaluated. Those animals that had blood glucose levels higher than 250 mg/dl were considered diabetic. Blood glucose levels of the rats were being measured by a glucometer after a 12 h fast. 21 Further, the healthy control rats were given intraperitoneal injections of normal saline at a dose of 1 cc to be in the same condition as diabetic groups.

Animals study design

In this experimental study, 24 male wistar rats randomly divided the following four groups, each with 6 animals: group I: non diabetic rats (ND-Cnt) which received water and normal food, without training; group II: diabetic control rats (D-Cnt) which received water and normal food, without training; group III: diabetic rats that received moderate-intensity continuous training (D-MICT), with water and normal food; group IV: diabetic rats that were treated with high-intensity interval training (D-HIIT) with water and normal food [23].

Training protocol

The moderate-intensity continuous training (D-MICT) and high-intensive interval training (D-HIIT) protocol was conducted on the treadmill 5 channel due to easier control speed and time. The diabetic rats in this groups training for 6 days/10 weeks, based on the protocol shown in Table 1.

Table 1.

moderate intensity continuous training (MICT) and high intensive interval training (HIIT) protocols [23]

Week Day MICT HIIT
Odd day Even day
Week1 1 20 min, 27 m/min 2intervals, 40 m/min, 3 min
2 22 min, 27 m/min 3intervals, 54 m/min, 30s
3 24 min, 27 m/min 2intervals, 40 m/min, 3 min
4 24 min, 27 m/min 5intervals, 54 m/min, 30s
5 28 min, 27 m/min 2intervals, 40 m/min, 3 min
6 30 min, 27 m/min 7intervals, 54 m/min, 30s
Week2 1 32 min, 27 m/min 3intervals, 40 m/min, 3 min
2 34 min, 27 m/min 9intervals, 54 m/min, 30s
3 36 min, 27 m/min 3intervals, 40 m/min, 3 min
4 38 min, 27 m/min 11intervals, 54 m/min, 30s
5 40 min, 27 m/min 3intervals, 40 m/min, 3 min
6 42 min, 27 m/min 13intervals, 54 m/min, 30s
Week3 1 44 min, 27 m/min 2intervals, 40 m/min, 3 min
2 46 min, 27 m/min 15intervals, 54 m/min, 30s
3 48 min, 27 m/min 4intervals, 40 m/min, 3 min
4 50 min, 27 m/min 17intervals, 54 m/min, 30s
5 52 min, 27 m/min 4intervals, 40 m/min, 3 min
6 54 min, 27 m/min 19intervals, 54 m/min, 30s
Week4 1 56 min, 27 m/min 5intervals, 40 m/min, 3 min
2 58 min, 27 m/min 19intervals, 54 m/min, 30s
3 60 min, 27 m/min 5intervals, 40 m/min, 3 min
4 60 min, 27 m/min 20intervals, 54 m/min, 30s
5 60 min, 27 m/min 6intervals, 40 m/min, 3 min
6 60 min, 27 m/min 20intervals, 54 m/min, 30s
Week5–10 1–6 60 min, 27 m/min to end of 10th week 6intervals, 40 m/min, 3 min to end of 10th week 20intervals, 54 m/min, 30s to end of 10th week
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Sampling and analysis of resistin, chemerin, insulin, FBG and lipid profile

28 h after the last exercise session, all of the rats were anaesthetized by anesthetized by intraperitoneal injection of ketamin (100 mg/kg) and zailazin (10 mg/kg) and sacrificed. Blood samples were collected by cardiac puncture (5 cc) and centrifuged at 3500 rpm for 5 min and the serum samples were stored at −80°c for future analysis. The serum levels of Resistin, Chemerin and Insulin in the study groups were assessments by ELISA method (ELISA plate reader Star Fax 2100, U.S.A) in accordance with the manufacturer’s instructions (Bioassay technology laboratory kits, Eastbiopharm, China). Resistin (Rat ELISA Kit, Eastbiopharm Cat.No CK-E30593, China, sensitivity: 2.52 pg/ml, Assay range: 5 pg/ml-1000 pg/ml), Chemerin (Rat ELISA Kit, Eastbiopharm Cat.No E1662Mo, China, sensitivity: 0.23 ng/ml, Assay range: 0.5-300 ng/ml), insulin (Rat ELISA Kit, Eastbiopharm Cat.No CK-E30620, China, sensitivity: 0.5mIU/L, Assay range: 0.1-40mIU/L). Serum concentration of fasting blood glucose (FBG), Alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), Gamma-Glutamyl Transferase (GGT), triglycerides (TG), total cholesterol (TC), and high-density lipoprotein (HDL) were measured enzymatically using commercial kits (Pars Azemoon, Tehran, Iran) by a spectrophotometer (JENWAY 6505, Europe Union). The serum low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) were calculated by the Friedewald formula [24] as follows: LDL(mg/dL) = TC(mg/dL) − HDL(mg/dL) − TG(mg/dL)/5 and VLDL = TG/5. It is noteworthy that the initial and final FBG as well as body weight of all rats was determined at 12-h fasting condition.

Statistical analysis

A Shapiro-Wilk test was applied to determine the normality of distribution of measures which were found to be normally distributed. Then a Leven test indicated that the variances were homogeneous. A one-way analysis of variance (ANOVA) was performed to determine the presence of differences among the groups. Significant differences were quantified using a post hoc test (Tuky). The data were expressed as means and standard error mean (SEM) of two replicates for six rats in each group. A P value <0.05 was considered statistically significant. Correlation between variables was also determined by pearson correlation coefficient. All statistical analyses were performed with GraphPad Prism software (Version 6.00).

Results

Fasting blood glucose and body weight of the experimental groups

As shown in Table 2, the baseline body weight of ND-Cnt and D-Cnt rats was increased (P > 0/05) at the day 70th of study. However, at the end of study duration the baseline body weight of D-MICT and D-HIIT rats less increased than ND-Cnt and D-Cnt. Also, at the end of study ND-Cnt as well as D-Cnt had a significantly higher values of body weight than D-MICT and D-HIIT rats (P < 0.05). Mean values of the baseline and end of study fasting blood glucose (FBG) levels in the experimental groups are demonstrated in Table 2. The baseline FBG levels in ND-Cnt significantly lesser than this levels D-Cnt (P < 0.001). There was not a significant difference between the baseline FBG levels of ND-Cnt as well as D-Cnt and the FBS levels at day 70th of study (P > 0.05). On the other hand, diabetic rats showed increased in FBG levels and administration of training at two protocol for 70 days significantly decreased this levels in comparison with D-Cnt (P = 0.001). The baseline FBG levels of D-MICT group and D-HIIT group was decreased significantly at day 70th of training (P = 0.001). At the end of study duration, significant difference was observed between two training methods (P = 0.001), i.e. that D-HIIT protocol has a better effect in lowering blood glucose.

Table 2.

Body weight and Fasting blood glucose (Means±SD)

Groups Body Weight (g) Fasting blood glucose (mg/dl)
Post test Pre test Post test Pre test
ND-Cnt 219.4 ± 71 250.4 ± 38 75.50 ± 13.7 86.83 ± 5.7
D-Cnt 223.6 ± 36 270.6 ± 48 269.0 ± 27.2a 340.5 ± 26.2a
D-MICT 224.3 ± 20 227.4 ± 38d 312.8 ± 23.1a 170.5 ± 54.56 a,b
D-HIIT 219.2 ± 80 224.7 ± 37d 384.2 ± 58.9a 128.2 ± 44.2a,b,c
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Abbreviations: ND-Cnt, non-diabetic control group; D-Cnt, diabetic control group; D-HIIT, diabetic high-intensive interval training training group; D-MICT, diabetic moderate-intensity continuous training group

aThe significant difference with ND-Cnt (p<0.05)

bThe significant difference with D-Cnt (p<0.05)

cThe significant difference with D-MICT (p<0.05)

dThe significant difference with D-HIIT (p<0.05)

Serum Resistin levels

These results were assessed at the end of the tenth week of training administration in all groups (Fig. 1). The difference between serum resistin levels of the ND-Cnt rats [123.6 ± 9, n = 6] and D-Cnt rats [140.3 ± 8.8, n = 6] was significant (P = 0.014). The effect of training on changes of the resistin levels in diabetic rats. Serum resistin levels in D-MICT rats was [117.8 ± 10.9, n = 6], while it was significantly higher than this levels in D-Cnt rats [140.3 ± 8.8, n = 6] (P = 0.002). Also, serum resistin levels in D-HIIT rats was [105.5 ± 12.9, n = 6], while it was significantly lower than this levels in D-Cnt rats [140.3 ± 8.8, n = 6] (P = 0.000). Notably, the serum resistin levels was not significantly in D-MICT rats compared to the D-HIIT rats (P = 0.058).

Fig. 1.

Fig. 1

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The effect of the different MICT and HIIT training on resistin serum levels in diabetic rat induced by streptozotocin-nicotinamide. *. Compared with Cnt group (P ≤ 0.05). # . Compared with D-Cnt group (P ≤ 0.05). One-way ANOVA followed by Tuky post-test were used. Values of P < 0.05 were considered statistically significant. All data are presented as Mean ± SEM; n = 6 for all groups; ND-Cnt: Non diabetic rats; D-Cnt: diabetic control rats or untrained diabetic rats; D-MICT: diabetic rats that received diabetic moderate-intensity continuous training; D-HIIT: diabetic rats that were trained with high intensive interval training

Serum Chemerin levels

These results were also evaluated at the end of the tenth week of training administration in all groups (Fig. 2). There was significant difference between serum chemerin levels of ND-Cnt rats [3.36 ± 0.38, n = 6] with D-Cnt [4.95 ± 1.24, n = 6] (P = 0.001). The values of serum chemerin levels in D-MICT [3.28 ± 1.02, n = 6] was significantly lower than in D-Cnt rats [4.95 ± 1.24, n = 6] (p = 0.004). As well as, serum chemerin levels in D-HIIT rats was [2.95 ± 0.64, n = 6] and it has significant differences compared with D-Cnt rats [4.95 ± 1.24, n = 6] (p = 0.001). It is worth to note, that the serum chemerin levels was not significantly higher in D-HIIT rats compared to the D-MICT rats (P = 0.525).

Fig. 2.

Fig. 2

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The effect of the different MICT and HIIT training on Chemerin serum levels in diabetic rat induced by streptozotocin-nicotinamide. *. Compared with Cnt group (P ≤ 0.05). # . Compared with D-Cnt group (P ≤ 0.05). One-way ANOVA followed by Tuky post-test were used. Values of P < 0.05 were considered statistically significant. All data are presented as Mean ± SEM; n = 6 for all groups; ND-Cnt: Non diabetic rats; D-Cnt: diabetic control rats or untrained diabetic rats; D-MICT: diabetic rats that received diabetic moderate-intensity continuous training; D-HIIT: diabetic rats that were trained with high intensive interval training

Serum insulin levels

Figure 3 shows the changes of insulin in normal and diabetic rats after training with D-MICT and D-HIIT for 70 days. There was a significant difference between serum insulin levels of ND-Cnt rats [3.18 ± 0.55, n = 6] with D-Cnt [4.93 ± 0.68, n = 6] (P = 0.001). Insulin secretion decreased significantly in D-MICT [3.08 ± 0.57, n = 6; P = 0.001] and D-HIIT [3.25 ± 0.82, n = 6; P = 0.001] training diabetic rats compared with D-Cnt [4.93 ± 0.68, n = 6] rats. Furthermore, It is worth to note, that the serum insulin levels were not significantly higher in D-HIIT rats compared to the D-MICT rats (P = 0.670).

Fig. 3.

Fig. 3

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The effect of the different MICT and HIIT training on Insulin serum levels in diabetic rat induced by streptozotocin-nicotinamide. *. Compared with Cnt group (P ≤ 0.05). # . Compared with D-Cnt group (P ≤ 0.05). One-way ANOVA followed by Tuky post-test were used. Values of P < 0.05 were considered statistically significant. All data are presented as Mean ± SEM; n = 6 for all groups; ND-Cnt: Non diabetic rats; D-Cnt: diabetic control rats or untrained diabetic rats; D-MICT: diabetic rats that received diabetic moderate-intensity continuous training; D-HIIT: diabetic rats that were trained with high intensive interval training

Serum liver enzyme levels

The effect of D-HIIT and D-MICT on Serum liver enzyme levels was shown in Table 3. The serum ALT, ALP, AST and GGT levels in the serum were significantly higher in D-Cnt than in the ND-Cnt rats (P < 0.05). The administration of D-HIIT significantly decreased the serum ALT, ALP, AST and GGT levels, compared to D-Cnt rats (P < 0.05). But, The administration of D-MICT significantly decreased just the serum ALP levels, compared to D-Cnt rats (P = 0.000).

Table 3.

Effect traninig administration of MICT and HIIT in serum liver enzyme levels in studied groups

Groups ALT (U/L) ALP (U/L) AST (U/L) GGT (U/L)
ND-Cnt 33.6 ± 10.9 273.3 ± 92.6 155.1 ± 46.9 1.0 ± 0.7
D-Cnt 136.5 ± 74.1a 2093.3 ± 219.8a 344.6 ± 196.2a 5.7 ± 2.5a
D-MICT 90.8 ± 46.1a 1119.5 ± 679.7a,b 267 ± 80.5 4.0 ± 1.7a
D-HIIT 44.3 ± 10.9b,c 548.5 ± 279.3b,c 156.8 ± 44.1b 3.2 ± 1.8b
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Abbreviations: ND-Cnt, non-diabetic control group; D-Cnt, diabetic control group; D-HIIT, diabetic high-intensive interval training training group; D-MICT, moderate-intensity continuous training group. ALT, Alanine Aminotransferase; ALP, Alkaline phosphatase; AST, Aspartate trans-aminase; GGT, Gamma-Glutamyl Transferase

aThe significant difference with D-Cnt (p < 0.05)

bThe significant difference with ND-Cnt (p < 0.05)

cThe significant difference with D-MICT (p < 0.05)

Serum lipid profile levels

The effect of MICT and HIIT training on lipid profile is shown in Table 4. The triglyceride, total cholesterol, VLDL and LDL levels in the serum were significantly higher in D-Cnt than in the ND-Cnt rats (P < 0.001). The administration of HIIT and MICT training significantly decreased these rum triglyceride, total cholesterol, VLDL and LDL levels, compared to D-Cnt rats (P < 0.001). Also, significantly decreased to almost the ND-Cnt rats (P < 0.001). Serum HDL was significantly lowered by diabetes induction (P < 0.001); however, it was significantly higher in D-HIIT and D-MICT training rats compared to the D-Cnt rats (P < 0.001). Notably, there was no significant difference between the effect of HIIT and MICT training administration in improving lipid profile (P > 0.05).

Table 4.

Effect of training administration of MICT and HIIT on serum lipids in studied groups

Groups Triglyceride (mg/dl) Total cholesterol (mg/dl) LDL (mg/dl) VLDL (mg/dl) HDL (mg/dl)
ND-Cnt 67 ± 5.2 53.6 ± 2.4 28.6 ± 0.9 13.3 ± 0.9 31.5 ± 1.9
D-Cnt 17.4 ± 130.5 70.6 ± 3.4 37.8 ± 1.9 24.3 ± 1.2 24.1 ± 1.1
D-MICT 7.3c,d ± 60.5 56 ± 3c,d 25.5 ± 0.9c,d 15.6 ± 3.2c,d 30.8 ± 1.7c,d
D-HIIT 5.5c,d,e ± 51.6 50.1 ± 4.6c,d,e 31.5 ± 2.8c,d,e 14 ± 1.6c,d,e 33.6 ± 1.6c,d,e
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Abbreviations: ND-Cnt, non-diabetic control group; D-Cnt, diabetic control group; D-HIIT, diabetic high-intensive interval training group; D-MICT, moderate-intensity continuous training group. LDL, low-density lipoprotein cholesterol; VLDL, very low-density lipoprotein cholesterol; HDL, high-density lipoprotein

aThe significant difference with D-Cnt (p < 0.05)

bThe significant difference with ND-Cnt (p < 0.05)

cThe significant difference with D-MICT (p < 0.05)

Correlation of serum Resistin and Chemerin with serum ALT, ALP, AST and GGT

As showed in Table 5, the serum resistin levels positively and significantly associated with values of serum ALP levels (r = 0.454, P = 0.026) in all groups (n = 24). Also, the serum chemerin levels positively and significantly associated with values of the serum ALT (r = 0.426, P = 0.038), ALP (r = 0.525, P = 0.008) and GGT (r = 0.622, P = 0.001) levels in all groups (n = 24).

Table 5.

Correlation of serum Resistin and Chemerin with serum ALT, ALP, AST and GGT in in all groups

Variable ALT (U/L) ALP (U/L) AST (U/L) GGT (U/L)
r p r p r p r p
(mg/L) Resistin 0. 320 0.127 0. 454 0.026* 0. 319 0.128 0. 260 0.220
Chemerin (ng/ml) 0. 426 0.038* 0. 525 0.008* 0. 255 0.230 0. 662 0.001*
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Abbreviations: ALT, Alanine Aminotransferase; ALP, Alkaline phosphatase; AST, Aspartate transaminase; GGT, Gamma Glutamyl transferase; r, correlation coefficient; P, P Value; *, significant

Discussion

In the present study, type 2 diabetes was induced by streptozotocin-nicotinamide (STZ-NA) injection in mice. Different animal models of type 2 diabetes have been diagnosed so far; and some researchers have been reported streptozotocin-nicotinamide-induced diabetes is a common type of type 2 diabetes in rats [25]. The present study showed that induction of diabetes increases the fast blood sugar, resistin, chemerin, liver enzymes and lipid profiles in diabetic rats than the control group. Also, in the present study, 10 weeks of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT), and subsequently, a significant decrease in blood glucose levels, resistin and chemerin led to improving the liver enzymes and lipid profile in trained diabetic rats than the diabetic control group. This result supports the positive effects of exercise and physical activity on controlling the glycemic in diabetic rats [26]. Furthermore, our results showed a significant increase in the serum levels, resistin and chemerin in diabetic groups, which had a positive and significant correlation with serum levels of ALT, ALP and GGT. These finding are consistent with the results of Asalah (2014) [14].

The liver plays an important role in regulating the glycemia under conditions of metabolic changes which occur during exercises by controlling the gluconeogenesis and blood glucose production [27]. On the one hand, in metabolic disorders such as diabetes, the liver is exposed to increases the oxidative stress and decreases the antioxidant defense capacity [28]. In the study of Schmatz et al. (2011), researchers showed that oxidative stress biomarkers improved by application of resveratrol supplementation and, subsequently, contents of AL and AST decreased in diabetic rats [29]. Exercises and sport activities create different adaptations in the body at different levels or different intensities so that such activities increasing the antioxidant capacity, and plays also two roles of prevention and therapy in oxidative stress-related diseases [30, 31]. Type 2 diabetes, in addition to hyperglycemia and hyperinsulinemia, causes the disturbances in production and metabolism of plasma lipoproteins whish known as a diabetic dyslipidemia. As well as, this disorder associated with increasing the triglyceride (TAG) and Low-density lipoprotein cholesterol (LDL-C) and decreasing the High-density lipoprotein cholesterol (HDL-C) [32].

Also, in streptozotocin–induced diabetic rats were accrued variety of disorders such as disorders in lipid profile which these have been associated with damage to liver tissue and increasing the liver enzymes [33]. The results of this study in relation to the treatment effects on lipid profile indices showed that TG, LDL, VLDL and total cholesterol traits were significantly reduced by application of MICT and HIIT exercises, although the HIIT was more effective than the MICT. Also, we found that content of HDL had a significant increase under using the treatments. Changes in blood lipids, such as triglyceride and LDL, can be related to response of lipoprotein lipase (LPL) to exercises. LPL is one of the lipoprotein regulating and triglyceride degrading enzymes in triglyceride-rich lipoproteins. Some researchers argue that sport activities can increase the activity of the LPL enzyme and reduce hepatic triglyceride lipase (HTGL) [34]. Accordingly, due to the fact that increasing the LPL activity increases the catabolism of triglyceride-rich lipoproteins, it can be concluded that LDL levels decrease with physical activities.

On the one hand, chemerin is an adipokine which was mainly expressed in adipose tissue, liver and kidney. Studies have shown that these adipokines also play a role in regulating the differentiation of adipose tissue and modulating the expression of genes involved in glucose and lipid homeostasis [35]. The adverse effects of chemerin on insulin signaling have been reported in adipose tissue at the in vitro. Based on this, Kralisch (2009) showed that chemerin regulate the insulin-stimulated glucose uptake in adipose tissue precursor cells (3 T3-L1), but on a decreasing trend [36]. In contrast to the above results, Takahashi (2008) reported that chemerin increases the sensitivity to insulin for adipose tissue precursor cells (3 T3-L1) [37]. It has also been observed that the level of chemerin serum was more common in diabetic patients and it was associated with inflammatory markers such as CRP, IL-6 and TNF-α, which it is the role of chemerin’s pre-inflammatory [38]. In addition, Buechler et al. (2014) reported that chemerin and chemerin’s receptors were significantly expressed in liver and chemerin plays an important role in the liver physiology and pathophysiology [39]. In confirming the later result, Lin et al., (2018) reported that 4 weeks of aerobic training lead to the significant reduce in expression of chemerin in liver of diabetic rats by STZ [40].

In addition, resistin is also express in the liver, while increasing the liver damage increase its production [8]. Recent studies have shown that resistin is one of the most important cytokines in the pathogenesis of liver diseases [41]. Some evidences stated that accumulation of resistin has power pre-inflammatory properties and it stimulate the release of many cytokines involved in inflammatory processes such as TNF-α, IL-1β, IL-6, and IL-12 [13]. In line with this, Palsamy et al., (2010) reported that the induction of diabetes by streptozotocin-nicotinamide in rats significantly increased the serum levels in TNF-α, IL-1β, IL-6 and then increased the serum levels in ALT, ALP and AST [42]. The present study showed that the HIIT training protocol reduced serum levels of resistin and subsequently it was decreased the ALT, ALP, AST and GGT serum levels in diabetic rats. In support the our results, Salemi et al., (2016) observed that application of Morus alba leaf extract for 6 weeks reduced the serum levels in resistin, ALP and AST [43]. Also, Hosseini et al., (2018) reported that HIIT training, for 6 weeks, significantly decreased the serum levels in diabetic rats [44].

Conclusion

Generally, in the present study we found that 10 weeks of moderate-intensity continuous training and high-intensity interval training decrease the serum levels in resistin and chemerin in training groups than the diabetic control group and due to the above, liver enzymes was improved and the level of serum insulin and fast blood glucose were decreased. These results may be caused by various mechanisms such as reducing the synthesis/diffusion of resistin and chemerin or reducing the expression of its receptor in liver. Understanding the concept of the relationship between resistin and chemerin and their relations with liver damage are very important for finding of new methods in therapeutic and preventive solutions against increasing the blood glucose. In fact, stimulation of resistin and chemerin and their receptors may be achieved a therapeutic approach for prevention and improvement of diabetes conditions by different training methods.

Abbreviations

ALT

Alanine aminotransferase

GGT

Gamma –glutamyltransferase

AST

Aspartate trans aminase

ALP

Alkaline phosphatase

HIIT

High-intensity interval training

MICT

Moderate-intensity continuous training

ND-Cnt

Non diabetic rats

D-Cnt

Diabetic control rats

D-MICT

Diabetic rats that received moderate-intensity continuous training

D-HIIT

Diabetic rats that were treated with high-intensity interval training

TAG

triglyceride

HDL-C

High-density lipoprotein cholesterol

LDL-C

Low-density lipoprotein cholesterol

Authors’ contributions

MP, EKH, AS, and ART were responsible for the study concept and design. MP, EKH, AS, and ART contributed to data acquisition. ELAMM, LFB, EKT, CAP and EAVM assisted with data analysis and interpretation of findings. MP, EKH, AS, and ART drafted the manuscript. All authors provided critical revision of the manuscript for important intellectual content and approved final version for publication.

Funding

Funding for this study was provided by Arak University. The funding sources had no other role other than financial support.

Data availability

The datasets used to analyze during this study are available from thecorresponding author on reasonable request.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the Ethical Committee of Experimental Animals of the Faculty of Medicine in Inonu Univer-sity, at which the studies were conducted.

Consent for publication

Not applicable.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Contributor Information

Parastesh Mohammad, Email: M-Parastesh@Araku.ac.ir.

Khosravi Zadeh Esfandiar, Email: E-Khosravizade@araku.ac.ir.

Saremi Abbas, Email: A-Saremi@araku.ac.ir.

Rekabtalae Ahoora, Email: mrekabtalae@gmail.com.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The datasets used to analyze during this study are available from thecorresponding author on reasonable request.

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