scholarly journals PEX-168 Improves Insulin Resistance, Inflammatory Response and Adipokines in Simple Obese Mice: A Mechanistic Exploration

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.


2021 ◽  
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.


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.


2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Jazyra Zynat ◽  
Yuyu Guo ◽  
Yingli Lu ◽  
Dongping Lin

Objectives. This study aimed to explore the expression of GLP-1 receptor in hypothalamus and gastrointestinal tissues after Roux-en-Y gastric bypass (RYGB) surgery in diabetic rats.Methods. Male 12-week-old Wistar rats (control) and Goto-Kakizaki rats (diabetic) were randomly divided into two groups, respectively: control sham surgery group (C), control RYGB group (C + R), diabetic sham surgery group (D), and diabetic RYGB group (D + R). Body weight and blood glucose were monitored before and after surgery every week. Eight weeks after surgery, all rats were sacrificed and the serum fasting GLP-1 concentrations were measured by ELISA. GLP-1R and DPP-4 expression in hypothalamus and ileum were measured by RT-PCR.Results. The body weight and fasting/random blood glucose in the D + R group decreased significantly compared with the D group (P<0.05). Serum GLP-1 levels in diabetic rats treated with RYGB were higher than the corresponding sham surgery rats. The expression of GLP-1R of hypothalamus in RYGB-treated diabetic rats was significantly higher than those of the sham surgery diabetic rats and both control group rats (P<0.05). We found a negative correlation between hypothalamus GLP-1R mRNA and blood glucose level. No significant difference was seen in ileum GLP-1R and DPP-4 expression among all groups.Conclusions. RYGB efficiently promoted serum GLP-1 levels and the expression of GLP-1 receptor in the hypothalamus in diabetic rats. These data suggest that the hypothalamus GLP-1R may play an important role in the GLP-1 system for improving glucose homeostasis after reconstruction of the gastrointestinal tract.


The aim of the study was to investigate the effects of Moringa oleifera aqueous seed extract on live body weight, gonadal and extragonadal dimensions and sperm reserves of Yankasa rams. Twenty five apparently healthy Yankasa rams aged 1-2 years and weighing 19.0 ± 2.1 Kg were used for the study. The rams were randomly selected into five groups: A, B, C, D and E with five rams in each group as treatment and control groups respectively. Groups A - D were given oral dose of Moringa oleifera aqueous seed extract at a dose rate of 1000, 2000, 3000, 4000 (mg/kg), respectively while group E was given 10 ml/kg water orally, daily for five months. Live body weight, gonadal and extragonadal reserves were determined according to standard techniques. The results showed a significant increase in live body weight in the months of April to June among rams treated with different doses of Moringa oleifera aqueous seed extract compared with the control group. The control group showed no significant differences in the body weight, gonadal and extragonadal dimensions and sperm reserves. In conclusion, the treatment of Yankasa rams with Moringa oleifera aqueous seed extract increased live body weight, but had no significant effects on gonadal and extragonadal dimensions and sperm reserves in Yankasa rams. Therefore, it is recommended that M. oleifera aqueous seed extract can be used at doses of 2000mg/kg to 3000mg/kg in Yankasa rams for optimum gain in live body weight.


2016 ◽  
Vol 36 (9) ◽  
pp. 901-909 ◽  
Author(s):  
D Sheela ◽  
R Vijayaraghavan ◽  
S Senthilkumar

Buprenorphine drug cartridge was made for autoinjector device for use in emergency and critical situations to reduce the morbidity and mortality. Water-filled cartridges were prepared and buprenorphine was injected aseptically in the cartridge, to make 0.05 and 0.10 mg/mL. Rats were injected intraperitoneally, buprenorphine (0.3 and 0.6 mg/kg), repeatedly with the autoinjector and compared with manual injection (7 days and 14 days) using various haematological and biochemical parameters. No significant change was observed in the body weight, organ to body weight ratio and haematological variables in any of the experimental groups compared with the control group. Except serum urea and aspartate aminotransferase, no significant change was observed in glucose, cholesterol, triglycerides, bilirubin, protein, albumin, creatinine, uric acid, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase. The autoinjectors deliver the drugs with spray effect and force for faster absorption. In the present study, the autoinjector meant for intramuscular injection was injected intraperitoneally in rats, and the drug was delivered with force on the vital organs. No significant difference was observed in the autoinjector group compared to the manual group showing tolerability and safety of the buphrenorphine autoinjector. This study shows that buprenorphine autoinjector can be considered for further research work.


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


2018 ◽  
Vol 52 (4) ◽  
pp. 185-191
Author(s):  
Tomomi Nobashi ◽  
Tsuneo Saga ◽  
Yuji Nakamoto ◽  
Yoichi Shimizu ◽  
Sho Koyasu ◽  
...  

AbstractObjective. This study investigated whether the metformin (Met)-induced enhanced intestinal uptake of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) is reduced by loperamide, a long-acting anti-diarrheal agent. Methods. Mean18F-FDG uptake in the mouse small intestine and colon with Met exposure was compared with that in control mice. In the Met group, high-dose (1.0 mg/kg body weight) and low-dose (0.1 mg/kg body weight) loperamide were introduced, and18F-FDG uptake in the small intestine and colon was compared with that of control mice administered high-dose loperamide. The percent injected dose of18F-FDG per gram of tissue (%ID/g) in the extracted tissues was then determined. Results.18F-FDG uptake increased significantly in the small intestine (0.64±0.06 vs. 1.01±0.15, p=0.040) and, especially, the colon (0.46±0.13 vs. 2.16±0.51, p<0.001) after Met exposure. Neither high-dose nor low-dose loperamide significantly reduced18F-FDG uptake in the small intestine (0.82±0.31 vs. 0.84±0.22, p=0.93 and 0.78±0.25 vs. 0.70±0.15, p=0.13, respectively) or colon (2.13±0.41 vs. 1.67±0.55, p=0.063 and 1.77±0.39 vs. 1.80±0.25, p=0.56, respectively). The colonic %ID/g was significantly higher in Met groups irrespective of loperamide introduction than in control group, whereas the significant difference in the small intestine was observed only between Met and control groups. Conclusion. Metformin increased18F-FDG uptake in intestines especially in colon. Loperamide administration partially, but not sufficiently, suppresses the Met-induced increased colonic uptake of18F-FDG.


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