A long-acting, dual-agonist analogue of lamprey GLP-1 shows potent insulinotropic, β-cell protective, and anorexic activities and improves glucose homeostasis in high fat-fed mice

Publication date: Available online 17 September 2019Source: Molecular and Cellular EndocrinologyAuthor(s): Galyna V. Graham, Andrew McCloskey, Yasser H. Abdel-Wahab, J. Michael Conlon, Peter R. FlattAbstractPeptidase-resistant analogues of GLP-1 peptides from sea lamprey and paddlefish ([D-Ala2]palmitoyl-lamprey GLP-1 and [D-Ala2]palmitoyl-paddlefish GLP-1) produced significant (P ≤ 0.05) and concentration-dependent increases in insulin release from BRIN-BD11 clonal β-cells and from isolated mouse islets. Both analogues retained the ability of the native peptides to activate both the GLP-1 receptor (GLP1R) and the glucagon receptor (GCGR). [D-Ala2]palmitoyl-lamprey GLP-1 significantly (P 
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research

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Conclusion Taken together, evidence from animal and human studies demonstrates that the brain detects levels of circulating nutrients and hormones and consequently organizes an outward response that contributes to the regulation of whole-body glucose homeostasis. However, there are major knowledge gaps about the exact nature of this response and its relative importance compared to peripheral processes. As we have seen, animal studies have provided an anatomical map of CNS glucose regulation and have identified important neurons and neural circuits involved. Additionally, the CNS sensing of key nutrients and hormones has b...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
We describe one such approach, albumin binding, and explain how it was applied in the development of the human GLP-1 analog liraglutide once daily and, subsequently, semaglutide once weekly. The pharmacology of these two long-acting GLP-1 analogs, in terms of improving glycemic control, reducing body weight and decreasing cardiovascular (CV) risk, is also reviewed, together with some novel biology. In addition, we describe the importance of accurate target (GLP-1 receptor) tissue expression analysis. Now an established class of agents, GLP-1-based therapies represent a significant advance in the treatment of T2D. All curr...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Conclusion Preclinical and clinical studies have demonstrated that treatment with antipsychotics and metformin had effects on the gut microbiota and the brain. Although the mechanism of the effects of metformin on AIMD remains unclear, there are some clues in the regulation of the gut-brain axis (Figure 1). The most important connections between metformin and AIMD in the gut microbiota were the mucin-degrading bacteria A. muciniphila and several SCFA-producing bacteria, such as the phyla Firmicutes and Bacteroidetes. The gut microbiota were was influenced during AIMD, and these changes included a decrease in A. muciniphil...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion: VS could play an important role in the treatment of metabolic syndrome, contributing to a decrease in obesity and T2DM, through different ways, such as euglycemia, satiety, weight loss, and lipid profile optimization, among others. However, more research is needed to confirm this suggestion. PMID: 30675160 [PubMed]
Source: International Journal of Endocrinology - Category: Endocrinology Tags: Int J Endocrinol Source Type: research
Conclusion: Phentermine–topiramate could be helpful for weight loss and reduction of binge-eating symptoms in patients with obesity or overweight in addition to BED. Controlled studies are warranted. Binge-eating disorder (BED), an eating disorder recognized in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), is characterized by recurrent and distressing episodes of binge eating (eating an unusually large amount of food with a sense of loss of control over eating) without inappropriate compensatory weight-loss behaviors.1 Known as the most common eating disorder, BED is strongly assoc...
Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Current Issue Drug Development Original Research binge eating obesity phentermine–topiramate Qsymia® weight loss Source Type: research
ConclusionsThese novel findings highlight the potential clinical utility of B12‐Ex4 conjugates as possible future T2DM therapeutics with reduced incidence of adverse effects.
Source: Diabetes, Obesity and Metabolism - Category: Endocrinology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Abstract Obesity has been an epidemic worldwide over the past decades and significantly increases the risk of developing a variety of deadly diseases including type 2 diabetes, cardiovascular diseases and many cancers. The relationship between obesity and type 2 diabetes and cardiovascular disease has been well documented. The drastically increased frequency of a number of cancers in obesity has attracted growing interest. On one hand, how increased adiposity promotes cancer development remains poorly understood, despite the fact that considerable epidemiological evidence has suggested links between them. On the other hand...
Source: IUBMB Life - Category: Research Authors: Tags: Critical Review Source Type: research
A high dose of liraglutide (3 mg), a human glucagon-like-peptide-1 (GLP-1) analog, which treats type 2 diabetes, was recently approved by the European Medicines Agency and United States Food and Drug Administration for weight reduction in human obesity [1].
Source: Diabetes Research and Clinical Practice - Category: Endocrinology Authors: Source Type: research
Volume 42, Issue 1, February 2017, Page 22-30 .
Source: Endocrine Research - Category: Endocrinology Authors: Source Type: research
My friend’s husband once said I’d be a great catch if I would just “lose a little more weight.” I was surprised by his comment, particularly since he carries around a spare tire and since I am healthy (and happy) in size. Unfortunately, he, like many others, believes that being a stick is a pre-requisite to being a “great catch.” Now, after reading Harriet Brown’s Body of Truth: How Science, History, and Culture Drive Our Obsession with Weight — and What We Can Do about It, I want us all to eradicate this kind of bizarre commentary and judgment. Body of Truth is hard to descr...
Source: Psych Central - Category: Psychiatry Authors: Tags: Anorexia Binge Eating Book Reviews Bulimia Diet & Nutrition General Healthy Living Personal Stories Policy and Advocacy Psychology Weight Loss Women's Issues americas diet industry anorexia in america being skinny isnt healthy Source Type: news
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