scholarly journals MS-275, a class 1 histone deacetylase inhibitor augments glucagon-like peptide-1 receptor agonism to improve glycemic control and reduce obesity in diet-induced obese mice

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Shilpak Bele ◽  
Shravan Babu Girada ◽  
Aramita Ray ◽  
Abhishek Gupta ◽  
Srinivas Oruganti ◽  
...  
Keyword(s):  
Body Weight ◽  
Histone Deacetylase ◽  
Therapeutic Potential ◽  
Combined Therapy ◽  
Chronic Administration ◽  
The Body ◽  
Short Term Treatment ◽  
Class 1 ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Given its glycemic efficacy and ability to reduce the body weight, glucagon-like peptide 1 receptor (GLP-1R) agonism has emerged as a preferred treatment for diabetes associated with obesity. We here report that a small-molecule Class 1 histone deacetylase (HDAC) inhibitor Entinostat (MS-275) enhances GLP-1R agonism to potentiate glucose-stimulated insulin secretion and decrease body weight in diet-induced obese (DIO) mice. MS-275 is not an agonist or allosteric activator of GLP-1R but enhances the sustained receptor-mediated signaling through the modulation of the expression of proteins involved in the signaling pathway. MS-275 and liraglutide combined therapy improved fasting glycemia upon short-term treatment and a chronic administration causes a reduction of obesity in DIO mice. Overall, our results emphasize the therapeutic potential of MS-275 as an adjunct to GLP-1R therapy in the treatment of diabetes and obesity.

scholarly journals How glucagon-like peptide 1 receptor agonists work

2021 ◽  
Author(s):  
Christine Rode Andreasen ◽  
Andreas Andersen ◽  
Filip Krag Knop ◽  
Tina Vilsbøll
Keyword(s):  
Body Weight ◽  
Therapeutic Potential ◽  
Clinical Effects ◽  
Glucose Lowering ◽  
Receptor Agonists ◽  
Reduce Body Weight ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Clinical Utilisation

Recent years, glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become central in the treatment of type 2 diabetes (T2D). In addition to their glucose-lowering properties with low risk of hypoglycaemia, GLP-1RAs reduce body weight and show promising results in reducing cardiovascular risk and renal complications in high-risk individuals with T2D. These findings have changed guidelines on T2D management over the last years, and GLP-1RAs are now widely used in overweight patients with T2D as well as in patients with T2D and cardiovascular disease regardless of glycaemic control. The currently available GLP-1RAs have different pharmacokinetic profiles and differ in their ability to improve glycaemia, reduce body weight and in their cardio- and renal protective potentials. Understanding how these agents work, including insights into their pleiotropic effects on T2D pathophysiology, may improve their clinical utilisation and be useful for exploring other indications such as non-alcoholic steatohepatitis and neurodegenerative disorders. In this review, we provide an overview of approved GLP-1RAs, their clinical effects and mode of actions, and we offer insights into the potential of GLP-1RAs for other indications than T2D. Finally, we will discuss the emerging data and therapeutic potential of using GLP-1RAs in combinations with other receptor agonists.

Efficacy and tolerability of pharmacological interventions on metabolic disturbance induced by atypical antipsychotics in adults: A systematic review and network meta-analysis

2021 ◽  
pp. 026988112110353
Author(s):  
Yewei Wang ◽  
Dandan Wang ◽  
Jie Cheng ◽  
Xinyu Fang ◽  
Yan Chen ◽  
...  
Keyword(s):  
Body Weight ◽  
Atypical Antipsychotics ◽  
Randomized Clinical Trials ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Metabolic Disturbance ◽  
Pharmacological Interventions ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Meta Analyses

Background: There have been a few systematic reviews and conventional meta-analyses reporting effect of drugs on metabolic disturbance induced by atypical antipsychotics (AAPs). However, few of them provided sufficient and comprehensive comparisons between pharmacological interventions. Aims: We aimed to qualitatively compare drugs’ effect on AAPs-induced metabolic abnormalities by using network meta-analysis (NMA). Methods: We searched PubMed, EMBASE, Web of Science, Cochrane Controlled Register of Trials (CENTRAL), and PsycINFO on March 26, 2019. Of 5889 records identified, 61 randomized clinical trials including 3467 participants were included. We estimated weighted mean difference (WMD) and odds ratio (OR) using NMA. We assessed the risk of bias of individual studies with the Review Manager 5.3. Primary outcomes included change of body weight and body mass index (BMI). Secondary outcomes included change of other cardiometabolic risk factors, acceptability, and tolerability. Results: For body weight, topiramate (WMD −5.4, 95% CI −7.12 to −3.68), zonisamide (−3.44, 95% CI −6.57 to −0.36), metformin (−3.01, 95% CI −4.22 to −1.83), glucagon-like peptide-1 receptor agonists (GLP-1RAs) (−3.23, 95% CI −5.47 to −0.96), and nizatidine (−2.14, 95% CI −4.01 to −0.27) were significantly superior to placebo. Results regarding to BMI were similar to that of body weight. With respect to tolerability, only topiramate (OR 24, 95% CI 3.15 to 648) was inferior to placebo. Conclusions: Considering both efficacy and tolerability, evidence from this NMA indicates zonisamide, metformin, GLP-1RAs, and nizatidine in adults should be the first-line treatment for alleviating AAPs-induced weight gain or elevated BMI.

scholarly journals Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

Bone ◽  
2015 ◽  
Vol 81 ◽  
pp. 459-467 ◽  
Author(s):  
M. Pereira ◽  
J. Jeyabalan ◽  
C.S. Jørgensen ◽  
M. Hopkinson ◽  
A. Al-Jazzar ◽  
...  
Keyword(s):  
Bone Mass ◽  
Trabecular Bone ◽  
Chronic Administration ◽  
Receptor Agonists ◽  
Trabecular Bone Mass ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Antiobesity and Hypolipidemic Activity of Moringa oleifera Leaves against High Fat Diet-Induced Obesity in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Souravh Bais ◽  
Guru Sewak Singh ◽  
Ramica Sharma
Keyword(s):  
Body Weight ◽  
Body Temperature ◽  
Total Cholesterol ◽  
High Fat Diet ◽  
Moringa Oleifera ◽  
Chronic Administration ◽  
The Body ◽  
Atherogenic Index ◽  
High Fat ◽  
Diet Induced Obesity

In the present study, the methanolic extract of Moringa oleifera leaves (MEMOL) was evaluated for antiobesity activity in rats. The antiobesity potential of MEMOL was studied against high fat diet-induced obesity (HFD) in rats. In this study, chronic administration of HFD in rats produced hypercholesterolemia (116.2 ± 0.27 mg/dL), which led to an increase in the body weight (225 gr), total cholesterol, triglycerides (263.0 ± 4.69 mg/dL), and attenuation in the levels of HDL (34.51 ± 2.20 mg/dL) as well as changes in body temperature of animals. Treatment of obese rats with MEMOL for 49 days resulted in a significant (P<0.001) change in body weight, total cholesterol, triglycerides, and LDL level along with a significant (P<0.001) increase in body temperature as compared to the HFD-induced obesity. MEMOL treated rats also showed a significant decrease in the level of liver biomarkers, organ weight, and blood glucose level. Further, rats treated with MEMOL (200 mg and 400 mg/kg) show reduced atherogenic index (1.7 ± 0.6 and 0.87 ± 0.76). The results indicate that the rats treated with Moringa oleifera (MO) have significantly attenuated the body weight without any change in the feed intake and also elicited significant thermogenic effect and to act as hypolipidemic and thermogenic property in obesity related disorders.

Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects

1998 ◽  
Vol 95 (6) ◽  
pp. 719-724 ◽  
Author(s):  
C. Mark B. EDWARDS ◽  
Jeannie F. TODD ◽  
Mohammad A. GHATEI ◽  
Stephen R. BLOOM
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Healthy Subjects ◽  
Therapeutic Potential ◽  
Double Blind ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released postprandially that stimulates insulin secretion, suppresses glucagon secretion and delays gastric emptying. The insulinotropic action of GLP-1 is more potent under hyperglycaemic conditions. Several published studies have indicated the therapeutic potential of subcutaneous GLP-1 in non-insulin-dependent (Type 2) diabetes mellitus. 2. We investigated whether subcutaneous GLP-1, at a dose shown to improve glycaemic control in early Type 2 diabetes, is insulinotropic at normal fasting glucose concentrations. A double-blind, randomized, crossover study of 10 healthy subjects injected with GLP-1 or saline subcutaneously after a 16 h fast was performed. The effect on cardiovascular parameters was also examined. 3. GLP-1 caused a near 5-fold rise in plasma insulin concentration. After treatment with GLP-1, circulating plasma glucose concentrations fell below the normal range in all subjects. One subject had symptoms of hypoglycaemia after GLP-1. A rise in pulse rate was found which correlated with the fall in plasma glucose concentration. An increase in blood pressure occurred with GLP-1 injection which was seen at the same time as the rise in plasma GLP-1 concentrations. 4. This study indicates that subcutaneous GLP-1 can override the normal homoeostatic mechanism maintaining fasting plasma glucose in man, and is also associated with an increase in blood pressure.

scholarly journals The experience with the clinical application of liralgutide (victosa), the first analog of human glucagon-like peptide-1 in the patients with type 2 diabetes mellitus - expanding the range of possibilities

2012 ◽  
Vol 58 (3) ◽  
pp. 51-55
Author(s):  
E N Ostroukhova ◽  
O K Khmel'nitskiĭ ◽  
E I Krasil'nikova ◽  
K S Davidenko
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Adverse Reactions ◽  
Brand Name ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

This paper reports the results of the treatment of 71 patients presenting with type 2 diabetes mellitus using liraglutide, a long-acting analog of glucagon-like peptide-1 (GLP-1) marketed under the brand name Victoza. Practically all the patients experienced either improvement or normalization of the parameters of carbohydrate metabolism in conjunction with a reduction of their body weight and arterial pressure. There were no severe hypoglycemic episodes and other adverse reactions to the therapy. It is recommended that Victoza should be more widely used for the treatment of the patients with type 2 diabetes mellitus.

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