scholarly journals Compound 18 Improves Glucose Tolerance in a Hepatocyte TGR5-dependent Manner in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2124 ◽  
Author(s):  
Marlena M. Holter ◽  
Margot K. Chirikjian ◽  
Daniel A. Briere ◽  
Adriano Maida ◽  
Kyle W. Sloop ◽  
...  

The bile acid receptor, TGR5, is a key regulator of glucose homeostasis, but the mechanisms by which TGR5 signaling improves glucose regulation are incompletely defined. In particular, TGR5 has an increasingly appreciated role in liver physiology and pathobiology; however, whether TGR5 signaling within the liver contributes to its glucoregulatory effects is unknown. Therefore, we investigated the role of hepatocyte TGR5 signaling on glucose regulation using a hepatocyte-specific TGR5 knockout mouse model. Hepatocyte-specific Tgr5Hep+/+ and Tgr5Hep−/− mice were fed a high fat diet (HFD) for 7 weeks and then orally gavaged with three doses of a highly potent, TGR5-specific agonist, Compound 18 (10 mg/kg), or vehicle, over 72 h and underwent an oral glucose tolerance test (OGTT) after the last dose. Herein, we report that TGR5 mRNA and protein is present in mouse hepatocytes. Cumulative food intake, body weight, and adiposity do not differ between Tgr5Hep+/+ and Tgr5Hep−/− mice with or without treatment with Compound 18. However, administration of Compound 18 improves glucose tolerance in Tgr5HEP+/+ mice, but not in Tgr5Hep−/− mice. Further, this effect occurred independent of body weight and GLP-1 secretion. Together, these data demonstrate that TGR5 is expressed in hepatocytes, where it functions as a key regulator of whole-body glucose homeostasis.

2020 ◽  
Vol 16 (1) ◽  
pp. 33-41
Author(s):  
Mohini C. Upadhye ◽  
Uday Deokate ◽  
Rohini Pujari ◽  
Vishnu Thakare

Background: Ficus glomerata (F. glomerata) Linn. Family Moraceace is a large tree found all over India including outer Himalayan ranges, Punjab, Chota Nagpur, Bihar, Orissa, West Bengal, Rajasthan, Deccan and also as a common plant in South India. It is planted around the home and temples. It is cultivated throughout the year, distributed in evergreen forests and moist localities. Objective: The Ethanolic Extract of roots of F. Glomerata (EEFG) belonging to the family Moraceace, was investigated for its antidiabetic activity using alloxan induced diabetic rats. Methods: Thirty rats were divided into 5 groups having 6 rats in each group. The alloxan was administered to the rats of all groups except normal control group through intraperitoneal route at a concentration of 140mg/kg body weight. A dose of 100mg/kg and 200 mg/kg body weight of EEFG was administered to alloxan induced diabetic rats. The administration of the extract was lasted for 11 days. Effectiveness of the extract on glucose, cholesterol, triglycerides, and high density lipoprotein and protein concentrations was analyzed. Results: Significant (p<0.05) reduction in the levels of glucose, cholesterol, triglyceride of the diabetic rats was observed after treatment with ethanolic extract. After subjecting to oral glucose tolerance test EEFG also showed significant improvement in glucose tolerance. Conclusion: F. glomerata root ethanolic extract showed that it possesses antidiabetic effect and can be found useful for the management of diabetes mellitus.


1996 ◽  
Vol 270 (5) ◽  
pp. E890-E894 ◽  
Author(s):  
G. Paolisso ◽  
A. Gambardella ◽  
S. Ammendola ◽  
A. D'Amore ◽  
V. Balbi ◽  
...  

Advancing age has been found to be associated with a decline in insulin action. Nevertheless, no study has been conducted in healthy centenarians. Our study investigates glucose tolerance and insulin action in centenarians. Fifty-two subjects were enrolled. The subjects were divided in three groups as follows: 1) adults (< 50 yr; n = 20);2) aged subjects (> 75 yr; n = 22); and 3) centenarians (> 100 yr; n = 14). Body composition was studied by bioimpedance analysis. In all subjects, an oral glucose tolerance test and euglycemic glucose clamp were performed. Centenarians have a lower fat-free mass (FFM) than aged subjects and adults, whereas fasting plasma glucose, triglycerides, free fatty acids, urea, and creatinine were not different in the groups studies. Centenarians had a 2-h plasma glucose concentration (6.0 +/- 0.2 mmol/l) that was lower than that in aged subjects (6.6 +/- 0.5 mmol/l, P < 0.05) but not different from adults [6.4 +/- 0.4 mmol/l, P = not significant (NS)]. During the clamp, plasma glucose and insulin concentrations were similar in the three groups. In these conditions, centenarians had a whole body glucose disposal (34.1 +/- 0.6 mumol.kg FFM-1.min 1) that was greater than that in aged subjects (23.3 +/- 0.5 mumol.kg FFM-1.min-1 P < 0.01) but not different from adults (34.6 +/- 0.5 mumol/kg x min, P = NS). In conclusion, our study demonstrates that centenarians compared with aged subjects had a preserved glucose tolerance and insulin action.


2021 ◽  
Vol 59 (3) ◽  
Author(s):  
Irena Crnić ◽  
Tajana Frančić ◽  
Petar Dragičević ◽  
Vedran Balta ◽  
Verica Dragović-Uzelac ◽  
...  

Research background. The use of plants and their extracts in treatments of chronic diseases is widely known in traditional medicine. The aim of this study is to determine the effects of 10-day consumption of Prunus spinosa L. flower extract on blood glucose, glycaemic load, serum α-amlyase and serum insulin, in normoglycaemic and hypergycaemic (alloxan) mice model. Experimental approach. Normoglycemic and hyperglycemic (alloxan treated, 150 mg/kg body mass) C57BL/6 mice were treated daily, during 10 days, with Prunus spinosa L. flower extract by gavage. The sugar content within extract was determined by HPLC analysis. In mice, blood and serum blood glucose level and OGTT-test were determined by blood glucometer. Serum insulin was determined by ELISA assay and α-amlyase by colourimetric assay. Results and conclusions. The Prunus spinosa L. flower extract increased glucose in normoglycaemic mice by 30 % after 1st and 5th day and by 17 % after 10th day of consumption in normoglycaemic mice. It is a consequence of released sugars because sugar analysis revealed 59.8 mg/L monosaccharides, mainly fructose (55.7 mg/L) and glucose (24.3 mg/L) within the extract. On the opposite, the extract consumption, reduced serum blood glucose in alloxan-induced hyperglycaemic mice by 29 % after 10 days of treatment. Oral glucose tolerance test also confirmed that that in the hyperglycaemic group treated with Prunus spinosa L. flower extract glucose homeostasis was improved and showed decrease in blood glucose, since the blood glucose over the period of 120 min, glucose homeostasis is faster achieved after treatment with shows that in Prunus spinosa L. flower extract. Serum insulin increased by 49 % and serum alpha amylase by 46 % after 10 days of treatment with Prunus spinosa L. flower extract in hyperglycaemic group. Thus, it can be concluded that Prunus spinosa L. flower extract improved glucose tolerance, enhanced insulin secretion and lowered serum α-amylase activity. Novelty and scientific contribution. The results examined for the first time the potential of Prunus spinosa L. flower extract in hyperglycaemia management.


Author(s):  
Lincoln A. Sargeant ◽  
Michael S. Boyne ◽  
Franklyn I. Bennett ◽  
Terrence E. Forrester ◽  
Richard S. Cooper ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3466
Author(s):  
Frédéric Nicolas Daussin ◽  
Alexane Cuillerier ◽  
Julianne Touron ◽  
Samir Ben Said ◽  
Bruno Melo ◽  
...  

Mitochondrial dysfunction is widely reported in various diseases and contributes to their pathogenesis. We assessed the effect of cocoa flavanols supplementation on mitochondrial function and whole metabolism, and we explored whether the mitochondrial deacetylase sirtuin-3 (Sirt3) is involved or not. We explored the effects of 15 days of CF supplementation in wild type and Sirt3-/- mice. Whole-body metabolism was assessed by indirect calorimetry, and an oral glucose tolerance test was performed to assess glucose metabolism. Mitochondrial respiratory function was assessed in permeabilised fibres and the pyridine nucleotides content (NAD+ and NADH) were quantified. In the wild type, CF supplementation significantly modified whole-body metabolism by promoting carbohydrate use and improved glucose tolerance. CF supplementation induced a significant increase of mitochondrial mass, while significant qualitative adaptation occurred to maintain H2O2 production and cellular oxidative stress. CF supplementation induced a significant increase in NAD+ and NADH content. All the effects mentioned above were blunted in Sirt3-/- mice. Collectively, CF supplementation boosted the NAD metabolism that stimulates sirtuins metabolism and improved mitochondrial function, which likely contributed to the observed whole-body metabolism adaptation, with a greater ability to use carbohydrates, at least partially through Sirt3.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Ahlam Mushtaq ◽  
Seema Akbar ◽  
Mohammad A. Zargar ◽  
Adil F. Wali ◽  
Akhtar H. Malik ◽  
...  

In the present study EtOAc, MeOH, and aqueous extracts ofEremurus himalaicuswere evaluated for hypoglycaemic effect in normal rats using both oral glucose tolerance test and 14-day oral administration study. Phytochemical and physicochemical screening was also done. In oral glucose tolerance test the aqueous and MeOH extracts ofEremurus himalaicusat a dose level of 500 mg/kg body weight prior to glucose load resulted in a significant fall in blood glucose level within 150 min. of glucose administration. The aqueous extract at a dose level of 250 mg/kg body weight and 500 mg/kg body weight also showed good hypoglycaemic response (P< 0.001); this was followed by MeOH extract at a dose level of 500 mg/kg body weight (P< 0.05), while MeOH extract at dose level of 250 mg/kg body weight and ethyl acetate extract at dose level of 250 mg/kg body weight and 500 mg/kg body weight exhibited insignificant effect. Phytochemical screening of extracts revealed the presence of alkaloids, terpenoids, phenolics, tannins, saponins, cardiac glycosides, and flavonoids. The results indicate that aqueous extract possess significant hypoglycaemic activity in normoglycaemic rats which may be attributed to the above-mentioned chemical constituents.


2019 ◽  
Vol 8 (7) ◽  
pp. 941-951 ◽  
Author(s):  
Gaëtan Prévost ◽  
Marie Picot ◽  
Marie-Anne Le Solliec ◽  
Arnaud Arabo ◽  
Hind Berrahmoune ◽  
...  

Objective Recent studies performed in mice revealed that the neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin and by increasing insulin sensitivity. However, in humans, an association between 26RFa and the regulation of glucose homeostasis is poorly documented. In this study, we have thus investigated in detail the distribution of 26RFa and its receptor, GPR103, in the gut and the pancreas, and determined the response of this peptidergic system to an oral glucose challenge in obese patients. Design and methods Distribution of 26RFa and GPR103 was examined by immunohistochemistry using gut and pancreas tissue sections. Circulating 26RFa was determined using a specific radioimmunoassay in plasma samples collected during an oral glucose tolerance test. Results 26RFa and GPR103 are present all along the gut but are more abundant in the stomach and duodenum. In the stomach, the peptide and its receptor are highly expressed in the gastric glands, whereas in the duodenum, ileum and colon they are present in the enterocytes and the goblet cells. In the pancreatic islets, the 26RFa/GPR103 system is mostly present in the β cells. During an oral glucose tolerance test, plasma 26RFa profile is different between obese patients and healthy volunteers, and we found strong positive correlations between 26RFa blood levels and the BMI, and with various parameters of insulin secretion and insulin resistance. Conclusion The present data suggest an involvement of the 26RFa/GPR103 peptidergic system in the control of human glucose homeostasis.


1983 ◽  
Vol 102 (4) ◽  
pp. 549-556 ◽  
Author(s):  
K. Berntorp ◽  
E. Trell ◽  
J. Thorell ◽  
B. Hood

Abstract. In a material of 3596 oral glucose tolerance tests (OGTT) performed in a population investigation of middle-aged males in Malmö, fasting and 120 min values of blood glucose and plasma insulin immunoreactivity (IRI) were studied while taking factors like body weight, smoking, alcohol, gastric resection and selfreported diabetes heredity into account. The fasting as well as the 120 min levels of both glucose and IRI were markedly influenced by body weight and smoking habits but not by the hereditary background. At 120 min, but not in the fasting state, there was a linear correlation between the IRI and glucose levels. The increase of IRI on glucose was significantly steeper in most of the hereditary subjects in comparison with their non-hereditary controls.


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