scholarly journals PEX-168 Improves Insulin Resistance, Inflammatory Response and Adipokines in Simple Obese Mice and Explore the Mechanism

Author(s):  
Guo Zeyuan ◽  
Wu Yuting ◽  
Sun Xiaofang

Abstract Background: Polyethylene glycxol losenatide(PEX-168)is a new anti-diabetic drug and there are no reports on its weight loss effects,so we designed this trial to investigate the effect of PEX-168 on simple obese mice. Methods: Thirty healthy C57BL/6 male mice were randomly selected and divided into a blank control group (NC, n=6) and an obesity model group (n=24), the high-fat diet-induced simple obesity mice were divided into a model control group (HF) and three different doses of PEX-168 intervention groups of low (LD), medium (MD) and high (HD) (the doses of PEX-168 were 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg), 6 animals in each group. The intervention groups were injected with different doses of PEX-168 intraperitoneally once a week for 12 weeks, and fasting blood glucose (FBG), body weight and food intake were measured from 1 to 12 weeks after the injection, and the activity of mice was observed, and serum insulin (INS), CRP, chemerin and omentin levels were measured after 12 weeks. Results: Compared with the HF group, the low dose of PEX-168 could reduce the body weight of mice in a short period of time (8 weeks), and the mice in the LD and HD groups had a significant decrease in body weight (P < 0.05);the low dose of PEX-168 could effectively improve the blood glucose and Homa-IR of mice (FBG P < 0.05 INS, IR P < 0.001), but there was no statistical difference between different doses (P > 0.05);CRP levels in HD and LD groups were significantly improved(P < 0.05),the levels of serum chemerin and omentin in intervention groups were significantly improved (P < 0.01), but there was no statistical difference between the different doses (P > 0.05). Conclusion: Continuous 12W administration of PEX-168 significantly reduced body weight in simple obese mice, thereby improving inflammatory status, improving insulin resistance, reducing serum chemerin level and increasing serum omentin level, inhibiting the development of diabetes. PEX-168 may regulate the expression of chemerin and omentin mainly through its hypoglycemic effect.

2021 ◽  
Author(s):  
Zeyuan Guo ◽  
Yuting Wu ◽  
Xiaofang Sun

Abstract Background:Polyethylene glycol losenatide (PEX-168) is a new antidiabetic drug; as such, there are not yet any reports on its weight loss effect. Therefore, this trial was designed to investigate the effect of PEX-168 on simple obese mice.Methods:Thirty healthy male C57BL/6 mice were randomly selected and divided into a control group (NC) and an obesity model group. The high-fat diet-induced simple obesity mice were divided into a model control group (HF) and three intervention groups. The intervention groups were injected with different doses of PEX-168 intraperitoneally once a week for 12 weeks (low (LD), medium (MD) and high (HD)). Fasting blood glucose (FBG), body weight and food intake were measured from 1 to 12 weeks after PEX-168 injection. The serum insulin (INS), C-reactive protein (CRP), chemerin and omentin levels were measured after 12 weeks.Results:Compared with the HF group, the low dose of PEX-168 reduced the body weight of the mice in a short period of time (8 weeks), and the mice in the LDand HD groups showed a significant decrease in body weight (P < 0.05). The low dose of PEX-168 could effectively improve the blood glucose and insulin resistance index (Homa-IR) of the mice (FBG P < 0.05 INS, Homa-IR P < 0.001), but there was no significant difference between different doses (P > 0.05). CRP levels in the HD and LD groups were significantly improved (P < 0.05). The levels of serum chemerin and omentin in the intervention groups were also significantly improved (P < 0.01), but there was no significant difference between the different doses (P > 0.05).Conclusion:PEX-168 significantly reduced the body weight of simple obese mice and prevented the development of diabetes. PEX-168 may regulate the expression of chemerin and omentin mainly through its hypoglycaemic effect, and the weight-reducing effect of PEX-168 is unlikely to be the reason for the changes in both.


2021 ◽  
Author(s):  
Zeyuan Guo ◽  
Yuting Wu ◽  
Sun Xiaofang

Abstract Background: Polyethylene glycol losenatide (PEX-168) is a new antidiabetic drug; as such, there are not yet any reports on its weight loss effect. Therefore, this trial was designed to investigate the effect of PEX-168 on simple obese mice.Methods: Thirty healthy male C57BL/6 mice were randomly selected and divided into a control group (NC, n=6) and an obesity model group (n=24). The high-fat diet-induced simple obesity mice were divided into a model control group (HF) and three intervention groups receiving different doses of PEX-168 (low (LD), medium (MD) and high (HD), receiving PEX-168 doses of 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, respectively), with 6 animals in each group. The intervention groups were injected with different doses of PEX-168 intraperitoneally once a week for 12 weeks. Fasting blood glucose (FBG), body weight and food intake were measured from 1 to 12 weeks after PEX-168 injection. The activity of the mice was observed, and serum insulin (INS), C-reactive protein (CRP) chemerin and omentin levels were measured after 12 weeks.Results: Compared with the HF group, the low dose of PEX-168 reduced the body weight of the mice in a short period of time (8 weeks), and the mice in the LD and HD groups showed a significant decrease in body weight (P < 0.05). The low dose of PEX-168 could effectively improve the blood glucose and insulin resistance index (Homa-IR) of the mice (FBG P < 0.05 INS, Homa-IR P < 0.001), but there was no significant difference between different doses (P > 0.05). CRP levels in the HD and LD groups were significantly improved (P < 0.05). The levels of serum chemerin and omentin in the intervention groups were also significantly improved (P < 0.01), but there was no significant difference between the different doses (P > 0.05).Conclusion: PEX-168 significantly reduced the body weight of simple obese mice and prevented the development of diabetes. PEX-168 may regulate the expression of chemerin and omentin mainly through its hypoglycaemic effect, and the weight-reducing effect of PEX-168 is unlikely to be the reason for the changes in both.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zeyuan Guo ◽  
Yuting Wu ◽  
Lihua Zhu ◽  
Yong Wang ◽  
Daorong Wang ◽  
...  

Abstract Background Polyethylene glycol loxenatide (PEX-168) is a new antidiabetic drug; as such, there are not yet any reports on its weight loss effect. Therefore, this trial was designed to investigate the effect of PEX-168 on simple obese mice. Methods Thirty healthy male C57BL/6 mice were randomly selected and divided into a control group (NC) and an obesity model group. The high-fat diet-induced simple obesity mice were divided into a model control group (HF) and three intervention groups. The intervention groups were injected with different doses of PEX-168 intraperitoneally once a week for 12 weeks (low (LD), medium (MD) and high (HD)). Fasting blood glucose (FBG), body weight and food intake were measured from 1 to 12 weeks after PEX-168 injection. The serum insulin (INS), C-reactive protein (CRP), chemerin and omentin levels were measured after 12 weeks. Results Compared with the HF group, the low dose of PEX-168 reduced the body weight of the mice in a short period of time (8 weeks), and the mice in the MD and HD groups showed a significant decrease in body weight (P < 0.05). The low dose of PEX-168 could effectively improve the blood glucose and homeostasis model assessment of insulin resistance (Homa-IR) of the mice (FBG P < 0.05 INS, Homa-IR P < 0.001), but there was no significant difference between different doses (P > 0.05). CRP levels in the MD and HD groups were significantly improved (P < 0.05). The levels of serum chemerin and omentin in the intervention groups were also significantly improved (P < 0.01), but there was no significant difference between the different doses (P > 0.05). Conclusions PEX-168 significantly reduced the body weight of simple obese mice and improved the insulin resistance. PEX-168 may regulate the expression of chemerin and omentin through its hypoglycaemic effect, and the weight-reducing effect of PEX-168 is unlikely to be the reason for the changes in both.


2015 ◽  
Vol 61 (4) ◽  
pp. 337-341
Author(s):  
Echim George ◽  
Sorina Cucuiet ◽  
Bianca Osz ◽  
Alexandra Grosan ◽  
Gal Zsolt ◽  
...  

AbstractAim: the purpose of the present study was to determine the effects of amisulpride at different doses on body weight, glucidic and lipidic metabolism.Material and method: Thirty-six white Wistar rats were treated daily for 9 weeks with amisulpride 1mg/kg and 10mg/kg body weight. Another group received distilled water and served as control group. At the end of the treatment period blood samples were collected and the follow biochemical parameters were determined: serum cholesterol, triglycerides, blood glucose, GOT, GPT. Body weight gain was also assessed weekly.Results: After treatment with amisulpride in doses of 1mg/kg and 10 mg/kg for a period of nine weeks, weight gains were recorded for both groups compared with the initial weight and the control group. Blood glucose concentrations in the group treated with 1 mg amisulpride/kg body weight were significantly increased (p<0.05 vs control group), but in the group treated with 10 mg/kg body weight glucose levels were not statistically significant increased compared to controls. Other biochemical parameters (cholesterol, triglycerides, GOT, GPT) showed no statistically significant differences compared to control group.Conclusions: amisulpride administered over a period of 9 weeks, in doses of 1mg/kg and 10mg/kg showed a slight increase of body weight regardless of gender, increased blood glucose only when was administered in the low dose, and does not affect lipid metabolism, even though decreased cholesterol and triglycerides levels. This results highlight a real benefit of treatment with amisulpride, comparatively with other athypical antipsychotics.


1969 ◽  
Vol 3 (2) ◽  
pp. 350-355
Author(s):  
MEENA GUL ◽  
MUHAMMAD MAZHAR HUSSAIN ◽  
AYESHA BABER ◽  
AMJAD ZAMAN ◽  
MUSRAT ZAHRA

BACKGROUND: Managing diabetes is difficult due to the number of side effects associated with drugsused for its treatment. There it is a need of an hour to look for indigenous plants which are safe and costeffective. Present study was planned to determine the effect of Aloe vera whole leaf extract and/orRosiglitazone on plasma glucose, insulin and insulin resistance in type 2 diabetic Sprague-Dawley rats.DESIGN: Randomized control trailPLACE AND DURATION OF STUDY: This study was conducted from April 2009 to Oct 2010 at theDepartment of Physiology Army Medical College, Rawalpindi in collaboration with National Institute ofHealth (NIH) Islamabad.MATERIAL AND METHOD: Type 2 DM was induced in 60 healthy Sprague-Dawley rats by feedinghigh fat diet for 2 weeks and injecting a low dose (35mg/kg) of streptozotocin intra peritoneally. Type 2diabetic rats were randomly divided into four groups, each group having 15 rats and were labeled as diabeticgroup, Aloe vera group, rosiglitazone group and combined group. The diabetic group was injected normalsaline, Aloe vera group was treated with Aloe vera whole leaf extract in dose of 300mg/kg body weight,rosiglitazone group was given 5mg/kg body weight of rosiglitazone I/P and combined group diabetic ratswere treated with 150mg/kg body weight of Aloevera extract and 2.5mg/kg body weight of rosiglitazone(halfof their effective dose) for 21 days.RESULTS: A significant reduction (p<0.001) in plasma glucose (73%), insulin (32%) and TG/HDL ratio(81%) was analyzed in combined groupascompared to diabetic control group. \CONCLUSION: The maximum impact in lowering plasma glucose, insulin and TG/HDL ratio wasrecorded in combined group, followed by rosiglitazone group and then Aloevera group.KEYWORDS:T2DM. Aloe vera, insulin resistance


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Seung Hwan Hwang ◽  
Il-Jun Kang ◽  
Soon Sung Lim

The objective of the present study was to evaluateα-glucosidase inhibitory and antidiabetic effects of Nopal water extract (NPWE) and Nopal dry power (NADP) in low-dose streptozotocin- (STZ-) induced diabetic rats fed a high-fat diet (HFD). The type 2 diabetic rat model was induced by HFD and low-dose STZ. The rats were divided into four groups as follows: (1) nondiabetic rats fed a regular diet (RD-Control); (2) low-dose STZ-induced diabetic rats fed HFD (HF-STZ-Control); (3) low-dose STZ-induced diabetic rats fed HFD and supplemented with NPWE (100 mg/kg body weight, HF-STZ-NPWE); and (4) low-dose STZ-induced diabetic rats fed HFD and supplemented with comparison medication (rosiglitazone, 10 mg/kg, body weight, HF-STZ-Rosiglitazone). In results, NPWE and NADP had IC50values of 67.33 and 86.68 μg/mL, both of which exhibit inhibitory activities but lower than that of acarbose (38.05 μg/mL) while NPWE group significantly decreased blood glucose levels compared to control and NPDP group on glucose tolerance in the high-fat diet fed rats model (P<0.05). Also, the blood glucose levels of HR-STZ-NPWE group were significantly lower (P<0.05) than HR-STZ-Control group on low-dose STZ-induced diabetic rats fed HFD. Based on these findings, we suggested that NPWE could be considered for the prevention and/or treatment of blood glucose and a potential use as a dietary supplement.


Author(s):  
Armanto Makmun ◽  
Rachmat Faisal Syamsu ◽  
Aisyah Jumadil ◽  
Rabia

Objective: The present study aimed to determine the potential effect of red onion extracts on ameliorating the blood glucose levels in alloxan-induced hyperglycemic mice.Material and Methods:Hyperglicemia was induced by single intramuscular injection of 70 mg/kg body weight of alloxan monohydrate. 24 mice were randomly assigned to four groups of 6 each including alloxan control (group AC), and three alloxan groups treated with doses 25 mg/kg body weight (group AR25), 50 mg/kg body weight (group AR50), and 100 mg/ kg body weight (group AR100) of red onion extracts. The latter three groups were treated with red onion extract for two weeks. The blood glucose levels were measured using a glucometer.Results and Discussion: The different doses of red onion extracts induced the different responses of blood glucose levels in hyperglycemia mice. The main finding of the present study revealed the significant capacity to ameliorate the blood glucose levels were shown in mice treated with 100 mg/kg body weight of red onion extracts (p<0.05).Conclusion: The red onion extracts at 100 mg/kg body weight significantly ameliorated the blood glucose in alloxan-induced hyperglycemic mice.International Journal of Human and Health Sciences Vol. 04 No. 02 April’20 Page : 98-101


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Camille Koffi ◽  
Raffaella Soleti ◽  
Mathieu Nitiema ◽  
Patricia Mallegol ◽  
Gregory Hilairet ◽  
...  

Despite long traditional utilization and some reports on the antihyperglycemic and antihyperlipidemic action of Cassia siamea, the mechanisms involved have not been investigated yet. Thus, the objective of the present study was to investigate whether and how oral administration of the ethanolic extract of Cassia siamea Lam leaves (LECS) improves glucose and insulin homoeostasis, liver damage, and endothelial dysfunction in an experimental model of type 2 diabetes, the leptin-deficient ob/ob mice. Oxidative stress and protein expression of insulin-dependent and insulin -independent signaling pathways were studied. Obese (ob/ob) vs. control (ob/+) mice were treated daily with intragastric administration of either vehicle or LECS (200 mg/kg, per day) for 4 weeks. Fasting blood glucose, body weight, food intake, glucose and insulin tolerance, oxidative stress, and liver damage as well as vascular complications with respect to endothelial dysfunction were examined. Administration of LECS in obese mice significantly reduced blood glucose and insulin levels, improved glucose tolerance and insulin sensitivity, and restored the increase of circulating AST and ALT without modification of body weight and food intake. These effects were associated with increased activity of both insulin and AMPK pathways in the liver and skeletal muscles. Of particular interest, administration of LECS in obese mice completely prevented the endothelial dysfunction resulting from an increased NO⋅ and decreased reactive oxygen species (ROS) production in the aorta. Altogether, oral administration of LECS remarkably attenuates features of type 2 diabetes on glucose, hepatic inflammation, insulin resistance, endothelial function, and vascular oxidative stress, being as most of these effects are related to insulin-dependent and insulin-independent mechanisms. Therefore, this study points for the therapeutic potential of Cassia siamea in correcting both metabolic and vascular alterations linked to type 2 diabetes.


Background: Hepatocellular damage caused by physical activity or the use of supplements is one of the serious problems facing athletes in various fields. This study aimed to evaluate the effect of different doses of nitric oxide supplements on AST and ALT liver enzymes and the ratio of AST to ALT following a session of eccentric exercise in Sprague Dawley male rats. Materials and Methods: In this study, 36 Sprague Dawley male rats (two months old) were divided into three groups of control, low dose (4.8 mg/kg body weight), and high dose of NO supplements (15.4 mg/kg body weight). Supplements were given to rats for seven days. Subsequently, all three groups of rats were forced to run on a treadmill for 45 min with a speed of 20 m/min, and a slope of -15 degrees. Blood samples were taken directly from cardiac puncture of rats 24 h after the running exercise. Blood serum variables of the study were measured afterward. Results: Low dose of nitrate supplements did not change AST and ALT indices, while the high dose of nitrate supplements increased ALT serum level and decreased AST to ALT ratio, compared to a low dose of NO supplements and control group. Conclusion: Based on the obtained results, the consumption of a low dose of NO supplements does not change hepatocellular damage markers, while the high dose of NO supplements causes degeneration of hepatic cells in athletes.


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