scholarly journals CB1 and GLP-1 receptors cross-talk provides new therapies for obesity

2020 ◽  
Author(s):  
Ada Admin ◽  
Philippe Zizzari ◽  
Rongjun He ◽  
Sarah Falk ◽  
Luigi Bellocchio ◽  
...  
Keyword(s):  
Body Weight ◽  
Negative Energy ◽  
Obese Mice ◽  
Preclinical Models ◽  
Metabolic Complications ◽  
Functional Interactions ◽  
Long Acting ◽  
Diabetes And Obesity ◽  
Neuropsychiatric Side Effects

GLP-1 receptor (GLP-1R) agonists effectively improve glycemia and body weight in patients with type 2 diabetes and obesity, but have limited weight-lowering efficacy and minimal insulin sensitizing action. In preclinical models, peripherally-restricted cannabinoid-1 receptor (CB1R) inhibitors, which are devoid of the neuropsychiatric side-effects observed with brain-penetrant CB1R blockers, ameliorate obesity and its multiple metabolic complications. Using mouse models with genetic loss of CB1R or GLP-1R, we demonstrate that these two metabolic receptors modulate food intake and body weight via reciprocal functional interactions. In diet-induced obese mice, the co-administration of a peripheral CB1R inhibitor with long-acting GLP-1R agonists achieves greater reduction in body weight and fat mass than monotherapies, by promoting negative energy balance. This co-treatment also results in larger improvements in systemic and hepatic insulin action, systemic dyslipidemia, and reduction of hepatic steatosis. Thus, peripheral CB1R blockade may allow safely potentiating the anti-obesity and anti-diabetic effects of currently available GLP-1R agonists.

scholarly journals CB1 and GLP-1 receptors cross-talk provides new therapies for obesity

2020 ◽  
Author(s):  
Ada Admin ◽  
Philippe Zizzari ◽  
Rongjun He ◽  
Sarah Falk ◽  
Luigi Bellocchio ◽  
...  
Keyword(s):  
Body Weight ◽  
Negative Energy ◽  
Obese Mice ◽  
Preclinical Models ◽  
Metabolic Complications ◽  
Functional Interactions ◽  
Long Acting ◽  
Diabetes And Obesity ◽  
Neuropsychiatric Side Effects

GLP-1 receptor (GLP-1R) agonists effectively improve glycemia and body weight in patients with type 2 diabetes and obesity, but have limited weight-lowering efficacy and minimal insulin sensitizing action. In preclinical models, peripherally-restricted cannabinoid-1 receptor (CB1R) inhibitors, which are devoid of the neuropsychiatric side-effects observed with brain-penetrant CB1R blockers, ameliorate obesity and its multiple metabolic complications. Using mouse models with genetic loss of CB1R or GLP-1R, we demonstrate that these two metabolic receptors modulate food intake and body weight via reciprocal functional interactions. In diet-induced obese mice, the co-administration of a peripheral CB1R inhibitor with long-acting GLP-1R agonists achieves greater reduction in body weight and fat mass than monotherapies, by promoting negative energy balance. This co-treatment also results in larger improvements in systemic and hepatic insulin action, systemic dyslipidemia, and reduction of hepatic steatosis. Thus, peripheral CB1R blockade may allow safely potentiating the anti-obesity and anti-diabetic effects of currently available GLP-1R agonists.

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.

scholarly journals I-M-150847, a novel GLP-1 and GIP receptor dual agonist, reduces body weight gain and improves glycemic control in the rodent model of type 2 diabetes and obesity.

2021 ◽  
Author(s):  
PRASENJIT MITRA ◽  
Rathin Bauri ◽  
Shilpak Bele ◽  
Jhansi Edelli ◽  
Sourav Dasadhikari ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Single Amino Acid ◽  
The Novel ◽  
Diabetes And Obesity ◽  
Dual Agonist ◽  
Gip Receptor

We report the discovery of a novel glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor dual agonist that shows balanced agonism towards both the incretin receptor. The dual agonism of GLP-1 and GIP receptor was achieved by replacing the tryptophan cage of exendin-4 with the C- terminal undecapeptide sequence of oxyntomodulin along with a single amino acid substitution from histidine to tyrosine at the amino terminus of the peptide. The structural modification places lysine 30 of the novel incretin agonist in frame with the corresponding lysine residue in the native GIP sequence. The novel incretin agonist, named I-M-150847, promotes robust glucose-stimulated insulin exocytosis in cultured pancreatic beta cells. Chronic administration of I-M-150847 to mice fed on the high-fat diet improves glucose tolerance, decreases food intake, decreases visceral adiposity and body weight gain demonstrating its therapeutic potential in ameliorating type 2 Diabetes and Obesity.

scholarly journals Dissolving microneedle-assisted long-acting Liraglutide delivery to control type 2 diabetes and obesity

2021 ◽  
pp. 106040
Author(s):  
Morteza Rabiei ◽  
Soheila Kashanian ◽  
Gholamreza Bahrami ◽  
Hossein Derakhshankhah ◽  
Ebrahim Barzegari ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Long Acting ◽  
Diabetes And Obesity

scholarly journals Efficacy and safety of short- and long-acting GLP-1 receptor agonists on a background of basal insulin in type 2 diabetes: A meta-analysis

2020 ◽  
Author(s):  
Jessica Annalena Huthmacher ◽  
Juris J. Meier ◽  
Michael A. Nauck
Keyword(s):  
Body Weight ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Basal Insulin ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Short Acting ◽  
Fasting Plasma ◽  
Long Acting

<b>Background/Purpose.</b> To compare efficacy and safety of short- and long-acting GLP-1 receptor agonists (GLP-1 RAs), both used in combination with basal insulin in patients with type 2 diabetes.<b></b> <p><b> </b></p> <p><b>Data Sources/Study Selection.</b><b><i> </i></b>Randomized controlled trials comparing the co-administration of short- or long-acting GLP-1 RAs and basal insulin with basal insulin ± placebo were identified (PubMed search). Of 974 identified publications 14 clinical trials were included. Eight trials examined short-acting and six long-acting GLP-1 RAs.<b></b></p> <p><b> </b></p> <p><b>Data Extraction/Data Synthesis.</b> Differences in HbA<sub>1c</sub>, fasting plasma glucose, body weight and adverse events were compared between studies using short- or long-acting GLP-1 RAs by random-effects meta-analysis.</p> <p><b> </b></p> <p><b>Limitations. </b>Relatively small numbers of available publications, some heterogeneity regarding protocols and differences in the GLP-1 RA compound used.</p> <p><b> </b></p> <p><b>Conclusions.</b> Long-acting GLP-1 RAs more effectively reduced HbA<sub>1c</sub> (∆ - 6 mmol/mol, [95 % CI - 10; - 2], p= 0.007), fasting plasma glucose (∆ - 0.7 mmol/l [- 1.2; - 0.3] p= 0.007) and body weight (∆ - 1.4 kg [- 2.2; - 0.6] p= 0.002) and raised the proportion of patients achieving an HbA<sub>1c</sub> target < 7.0% (< 53 mmol/mol; p= 0.03) more than the short-acting ones. Patients reporting symptomatic (p= 0.048), but not severe hypoglycemia (p= 0.96) were fewer with long- vs. short-acting GLP-1 RAs added to insulin. The proportion of patients reporting nausea (- 52 %; p < 0.0001) or vomiting (- 36 %; p= 0.0002) was lower with long-acting GLP-1 RAs.<b> </b>Overall, GLP-1 RAs improved HbA<sub>1c</sub>, fasting plasma glucose and body weight when added to basal insulin. However, long-acting GLP-1 RAs were significantly more effective for glycemic and body weight control and displayed better gastro-intestinal tolerability. </p>

scholarly journals Polyphenol-Rich Fraction of Brown AlgaEcklonia cavaCollected from Gijang, Korea, Reduces Obesity and Glucose Levels in High-Fat Diet-Induced Obese Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Eun Young Park ◽  
Eung Hwi Kim ◽  
Mi Hwi Kim ◽  
Young Wan Seo ◽  
Jung Im Lee ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Glucose Tolerance ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Obese Mice ◽  
High Fat ◽  
Glucose Levels

Ecklonia cava (E. cava)is a brown alga that has beneficial effects in models of type 1 and type 2 diabetes. However, the effects ofE. cavaextracts on diet-induced obesity and type 2 diabetes have not been specifically examined. We investigated the effects ofE. cavaon body weight, fat content, and hyperglycemia in high-fat diet- (HFD) induced obese mice and sought the mechanisms involved. C57BL/6 male mice were fed a HFD (60% fat) diet or normal chow. After 3 weeks, the HFD diet group was given extracts (200 mg/kg) ofE. cavaharvested from Jeju (CA) or Gijang (G-CA), Korea or PBS by oral intubation for 8 weeks. Body weights were measured weekly. Blood glucose and glucose tolerance were measured at 7 weeks, and fat pad content and mRNA expression of adipogenic genes and inflammatory cytokines were measured after 8 weeks of treatment. G-CA was effective in reducing body weight gain, body fat, and hyperglycemia and improving glucose tolerance as compared with PBS-HFD mice. The mRNA expression of adipogenic genes was increased, and mRNA expression of inflammatory cytokines and macrophage marker gene was decreased in G-CA-treated obese mice. We suggest that G-CA reduces obesity and glucose levels by anti-inflammatory actions and improvement of lipid metabolism.

scholarly journals A Long-Acting FGF21 Molecule, PF-05231023, Decreases Body Weight and Improves Lipid Profile in Non-human Primates and Type 2 Diabetic Subjects

2016 ◽  
Vol 23 (3) ◽  
pp. 427-440 ◽  
Author(s):  
Saswata Talukdar ◽  
Yingjiang Zhou ◽  
Dongmei Li ◽  
Michelle Rossulek ◽  
Jennifer Dong ◽  
...  
Keyword(s):  
Body Weight ◽  
Lipid Profile ◽  
Long Acting ◽  
Type 2 Diabetic
Sign in / Sign up

Export Citation Format

Share Document