scholarly journals The influence of novel GPR119 agonist on body weight, food intake and glucose metabolism in obesity rats provoked high-fat and -carbohydrate diet

2016 ◽  
Vol 62 (1) ◽  
pp. 44-49 ◽  
Author(s):  
Ivan Nikolaevich Tiurenkov ◽  
Denis Vladimirovich Kurkin ◽  
Dmitry Aleksandrovich Bakulin ◽  
Elena Vladimirovna Volotova ◽  
Mikhail Ayratovich Chafeev

The search for new drugs for the treatment of type 2 diabetes mellitus (T2DM) and obesity remains an urgent problem. Drugs with influence on incretin system are widely used in the treatment of T2DM and obesity, since in addition to the hypoglycemic action of their inherent hypophagic effects. With the discovery of GPR119 receptor, there is the opportunity to pharmacological stimulation of endogenous secretion of incretins. Compound ZB-16 is active GPR119 agonist with IC50=7 nM. Its activation leads to increased secretion of the major incretins (GLP-1 and GIP), which are able to influence glucose metabolism and feeding behavior.Aims — to study the effect of GPR 119 receptor agonist compounds ZB-16 on blood glucose, body weight and food intake in rats with obesity.Material and methods.Male rats with initial weight 390—400 g were fed with high-carbohydrate and high-fat diet. During the next four weeks the animals orally received ZB-16 (1 mg/kg) and metformin (400 mg/kg) and then we assessed the level of water and food consumption, blood glucose levels, and performed oral glucose tolerance test (OGTT).Results.Compound ZB-16 and metformin reduced fasting blood glucose levels and weight of experimental animals, while the control rats gained weight. GPR119 agonist is more pronounced than metformin reduced the area under the curve «glucose of concentration—time» during the OGTT.Conclusions.Novel GPR119 agonist — ZB-16 is comparable to metformin in hypoglycemic and anorexigenic effect in animals with obesity caused high-carbohydrate and high-fat diet.

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.


2020 ◽  
Vol 23 (1) ◽  
Author(s):  
Hye-Won Yang ◽  
Myeongjoo Son ◽  
Junwon Choi ◽  
Seyeon Oh ◽  
You-Jin Jeon ◽  
...  

Abstract Brown alga (Ishige okamurae; IO) dietary supplements have been reported to possess anti-diabetic properties. However, the effects of IO supplements have not been evaluated on glucose metabolism in the pancreas and skeletal muscle. C57BL/6 N male mice (age, 7 weeks) were arranged in five groups: a chow diet with 0.9% saline (NFD/saline group), high-fat diet (HFD) with 0.9% saline (HFD/saline group). high-fat diet with 25 mg/kg IO extract (HFD/25/IOE). high-fat diet with 50 mg/kg IO extract (HFD/50/IOE), and high-fat diet with 75 mg/kg IO extract (HFD/75/IOE). After 4 weeks, the plasma, pancreas, and skeletal muscle samples were collected for biochemical analyses. IOE significantly ameliorated glucose tolerance impairment and fasting and 2 h blood glucose level in HFD mice. IOE also stimulated the protein expressions of the glucose transporters (GLUTs) including GLUT2 and GLUT4 and those of their related transcription factors in the pancreases and skeletal muscles of HFD mice, enhanced glucose metabolism, and regulated blood glucose level. Our results suggest Ishige okamurae extract may reduce blood glucose levels by improving glucose metabolism in the pancreas and skeletal muscle in HFD-induced diabetes.


10.5219/1136 ◽  
2019 ◽  
Vol 13 (1) ◽  
pp. 644-650 ◽  
Author(s):  
Ahdiyatul Fauza ◽  
Ahmad Ni'matullah Al-Baarri ◽  
Kis Djamiatun

T2DM has increase in global-morbidity and mortality. Oxidative stress and adiponectin-levels are important for insulin-resistance and pancreatic-b-cell-dysfunction in T2DM. Okra fruit is rich of quercetin and phytosterol which have positive-effect for T2DM. Research aimed was to study the effect of okra-flour to adiponectin-levels and total-antioxidant-capacity (TAC) in T2DM. Thirty Wistar-rats were divided randomly in five groups. K1 and (X1, X2 and X3)-treated-groups were in T2DM-condition-induced by high-fat-diet-(HFD)-Streptozotochin-(STZ)-nicotinamid-(NA). Healthy-controls-(K2)-group was also used. Okra-flour was given orally for 28 days at doses of 0.1; 0.2 and 0.3 g/Kg-body-weight/d to X1, X2 and X3-groups, respectively. Statistical program was used to analyse the different between pre-post-intervention, and between groups. Correlations between variables were also analysed. The serum-adiponectin and TAC-levels were measured by ELISA and ABTS-methods, respectively. By comparing pre and post-intervention, adiponectin levels of all-intervention-(X1, X2, X3)-group were  increase (p = 0.027 for X1 and X2; p = 0.028 for X3), while in the same period the decrease were found in group K1 (p = 0.026) and K2 (p = 0.028). Increase-TAC-levels pre-post-intervention was observed in group all-intervention-groups (p = 0.027), while no change in K1 (p = 0.66) and the decrease in group K2 (p = 0.039). Reduce-fasting-blood-glucose-levels pre-post-intervention were shown in the all-intervention-groups (p = 0.028), while for the K1 groups was increase (p = 0.028). There were significant differences between the five-groups on fasting-blood-glucose-levels, adiponectin and TAC-levels, and X3-group showed the highest adiponectin and TAC-levels. Very-strong-correlations were found between glucose-adiponectin-TAC-levels-post-intervention. Okra-flour make better glucose-adiponectin and TAC-levels in T2DM-conditions. Okra dose of 0.30 g/Kg-body-weight/day is the best in increasing adiponectin and TAC-levels.


2020 ◽  
Author(s):  
Yao Zhang ◽  
jiao Zhang ◽  
Ming Hong ◽  
Jingyi Huang ◽  
Rui Wang ◽  
...  

Abstract BackgroundOptimization of experimental conditions in streptozotocin induced diabetic model in Sprague Dawley (SD) rats to evaluate the stability of the model.MethodsMale and female SD rats were randomly divided into control group, STZ 45 group (STZ: 45 mg / kg), STZ 65 group (STZ: 65 mg / kg), STZ 85 group (STZ: 85 mg / kg), high fat diet with STZ 45 group (STZ: 45 mg / kg), high fat diet with STZ 65 group (STZ: 65 mg / kg), high fat diet with STZ 85 group (STZ: 85 mg / kg). N = 6 in each group. The changes of body weight and blood glucose were observed dynamically.ResultsThere was no significant difference in blood glucose or body weight between the STZ 45 group and the control group in both male and female rats, whether or not they were on a high-fat diet. However, there were significant differences in blood glucose between the high-dose STZ group and the control group in both male and female rats, regardless of whether the rats were on a high-fat diet or not (P < 0.05 or P < 0.01). Compared with the control group, there were significant differences in blood glucose levels (P < 0.05 or P < 0.01) and higher blood glucose levels in the male rats fed with the normal diet than that in those fed with the high-fat diet.ConclusionsIn this study, male rats fed with ordinary feed and injected STZ dose of 65 mg / kg were the most stable and ideal diabetic rat.


2012 ◽  
Vol 48 (3) ◽  
pp. 647-653 ◽  
Author(s):  
Yusuke Sakurai ◽  
Hiroaki Inoue ◽  
Norihito Shintani ◽  
Akihiro Arimori ◽  
Ken-ichi Hamagami ◽  
...  

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 645
Author(s):  
Jing-Yi Chen ◽  
Shao-Yu Peng ◽  
Yeong-Hsiang Cheng ◽  
I-Ta Lee ◽  
Yu-Hsiang Yu

The purpose of this study was to investigate the effects of forskolin on body weight, glucose metabolism and fat cell diameter in high-fat diet-induced obese mice. Four-week-old male mice (C57BL/6) were randomly assigned to 1 of 3 treatment groups: a high-fat diet plus 5% dimethyl sulfoxide (vehicle), high-fat diet plus 2 mg/kg of forskolin (dissolved in 5% dimethyl sulfoxide) and high-fat diet plus 4 mg/kg of forskolin (dissolved in 5% dimethyl sulfoxide). Forskolin or dimethyl sulfoxide was administered intraperitoneally every two days. The results indicated that no significant difference was observed in the body weight, feed intake and serum lipid parameters among groups at 20 weeks of age. The blood glucose levels were significantly reduced in the groups treated with 2 mg/kg of forskolin before glucose tolerance test. Forskolin administration linearly decreased blood glucose levels of high-fat diet-fed mice at 90 min and total area under curve (AUC) after insulin tolerance test. The subcutaneous adipocyte diameter was significantly reduced in the groups treated with 2 mg/kg of forskolin. Forskolin administration linearly reduced the gonadal adipocyte diameter of high-fat diet-fed mice. Forskolin significantly reduced the differentiation of murine mesenchymal stem cells into adipocytes and this was accompanied by a decrease in intracellular triglyceride content and an increase in glycerol concentration in the culture medium. The subcutaneous adipocyte diameter, gonadal adipocyte diameter and total AUC of insulin tolerance test were moderately negatively correlated with the concentration of forskolin in the high-fat diet-induced obese model. These results demonstrate that forskolin can regulate glucose metabolism and reduce fat cell diameter of high-fat diet-fed mice and inhibit the adipocyte differentiation of murine mesenchymal stem cells.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Katsunori Nonogaki ◽  
Miki Hazama ◽  
Noriko Satoh

Social isolation contributes to the development of obesity and insulin-independent diabetes in KKAymice. Here we show that systemic administration of liraglutide, a long-acting human glucagon-like peptide-1 (GLP-1) analog, significantly decreased food intake, body weight, and blood glucose levels at 24 h after its administration while having no significant effects on plasma insulin and glucagon levels in individually housed KKAymice. In addition, the systemic administration of liraglutide significantly increased plasma fibroblast growth factor (Fgf) 21 levels (1.8-fold increase) associated with increases in the expression of hepaticFgf21(1.9-fold increase) andPparγ(1.8-fold increase), while having no effects on the expression of hepaticPparαandFgf21in white adipose tissue. Moreover, systemic administration of liraglutide over 3 days significantly suppressed food intake, body weight gain, and hyperglycemia in KKAymice. On the other hand, despite remarkably increased plasma active GLP-1 levels (4.2-fold increase), the ingestion of alogliptin, a selective dipeptidyl peptidase-4 inhibitor, over 3 days had no effects on food intake, body weight, blood glucose levels, and plasma Fgf21 levels in KKAymice. These findings suggest that systemic administration of liraglutide induces hepatic Fgf21 production and suppresses the social isolation-induced obesity and diabetes independently of insulin, glucagon, and active GLP-1 in KKAymice.


2015 ◽  
Vol 228 (2) ◽  
pp. 115-125 ◽  
Author(s):  
Tetsuya Kouno ◽  
Nobuteru Akiyama ◽  
Takahito Ito ◽  
Tomohiko Okuda ◽  
Isamu Nanchi ◽  
...  

Ghrelin is an appetite-stimulating hormone secreted from stomach. Since the discovery that acylation of the serine-3 residue by ghrelin O-acyltransferase (GOAT) is essential for exerting its functions, GOAT has been regarded as an therapeutic target for attenuating appetite, and thus for the treatment of obesity and diabetes. However, contrary to the expectations, GOAT-knockout (KO) mice have not shown meaningful body weight reduction, under high-fat diet. Here, in this study, we sought to determine whether GOAT has a role in body weight regulation and glucose metabolism with a focus on dietary sucrose, because macronutrient composition of diet is important for appetite regulation. We found that peripherally administered acylated-ghrelin, but not unacylated one, stimulated sucrose consumption in a two-bottle-drinking test. The role of acylated-ghrelin in sucrose preference was further supported by the finding that GOAT KO mice consumed less sucrose solution compared with WT littermates. Then, we investigated the effect of dietary composition of sucrose on food intake and body weight in GOAT KO and WT mice. As a result, when fed on high-fat diet, food intake and body weight were similar between GOAT KO and WT mice. However, when fed on high-fat, high-sucrose diet, GOAT KO mice showed significantly reduced food intake and marked resistance to obesity, leading to amelioration of glucose metabolism. These results suggest that blockade of acylated-ghrelin production offers therapeutic potential for obesity and metabolic disorders caused by overeating of palatable food.


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