scholarly journals Gut microbiota is an endocrine organ

2020 ◽  
Vol 17 (3) ◽  
pp. 299-306
Author(s):  
Tatiana Y. Demidova ◽  
Kristina G. Lobanova ◽  
Olga S. Oynotkinova
Keyword(s):  
Gut Microbiota ◽  
Active Metabolites ◽  
Local Immunity ◽  
Endocrine Organ ◽  
Intestinal Peristalsis ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Organ Changes ◽  
Diabetes And Obesity ◽  
Synthesis Of Hormones

The gut microbiota affects the processes of food digestion, intestinal peristalsis, controls the work of the intestinal epithelium, has protective properties against pathogenic microorganisms, activating local immunity and stimulating the secretion of mucus by intestinal cells. Besides the gut microbiota participates in the metabolism of proteins, fats and carbohydrates, mediates the processes of gluconeogenesis, glycogenolysis, lipogenesis and lipolysis, and affects on feelings of hunger and satiety. All these processes occur because the gut microbiota produces active metabolites throughout their life activity. Gut microbiota and active metabolites of the gut microbiota activate the synthesis of hormones. The gut microbiota affects the synthesis of hormones such as glucagon-like peptide-1, glucagon-like peptide-2, YY-peptide, glucose-dependent insu-linotropic peptide, ghrelin, leptin, cholecystokinin, serotonin, and insulin. Disturbance of the secretion of these hormones is one of the links in the pathogenesis of endocrine diseases such as diabetes and obesity. Thus, the gut microbiota is an endocrine organ. Changes in the composition and functions of the gut microbiota lead to metabolic disorders.This article describes the effect of gut germs and active metabolites of the gut microbiota on the synthesis hormones by means of receptor mechanisms, genes, and enzymes.

Liraglutide for psychiatric disorders: clinical evidence and challenges

2018 ◽  
Vol 36 (2) ◽  
Author(s):  
Mehmet Akif Camkurt ◽  
Luca Lavagnino ◽  
Xiang Y. Zhang ◽  
Antonio L Teixeira
Keyword(s):  
Risk Factors ◽  
Psychiatric Disorders ◽  
Clinical Evidence ◽  
Preclinical Studies ◽  
Potential Candidate ◽  
Obesity And Diabetes ◽  
Treatment Of Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Diabetes And Obesity

Abstract Obesity and diabetes are both risk factors and consequences of psychiatric disorders. Glucagon like peptide 1 (GLP-1) receptor agonists such as liraglutide are widely used in the treatment of diabetes and obesity. There are considerable amounts of preclinical studies showing the effects of liraglutide on promotion of neurogenesis, while preventing apoptosis and oxidation. Preliminary clinical evidence has suggested that liraglutide could decrease weight gain, improve cognition and prevent cognitive decline. Accordingly, liraglutide has been regarded as a potential candidate for the management of psychiatric disorders. Herein, we will discuss the association between obesity/diabetes and psychiatric disorders, and the emerging use of liraglutide in psychiatry.

scholarly journals Gut Microbiota Play an Essential Role in the Antidiabetic Effects of Rhein

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ruifeng Wang ◽  
Pu Zang ◽  
Junxiu Chen ◽  
Fei Wu ◽  
Zhouqin Zheng ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Essential Role ◽  
Fasting Blood Glucose ◽  
Shannon Index ◽  
Simpson Index ◽  
Significant Difference ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Host Metabolism ◽  
Antidiabetic Effects

It is clear that the gut microbiota can affect host metabolism and alterations of the gut microbiota can link with metabolic disease. Rhein has been used in traditional Chinese medicine with putative antidiabetic effects. Here we show that oral administration of rhein for 6 weeks can significantly reduce fasting blood glucose (FBG) level (8.30 ± 4.52 mmol/l versus 18.89 ± 6.06 mmol/l, p < 0.01), elevate the active glucagon-like peptide 1 (GLP-1) level (22.21 ± 2.61 pmol/l verss 14.46 ± 5.22 pmol/l, p < 0.05), and increase the number of L-cells in the terminal ileum. The antidiabetic effect of rhein is abrogated in db/db mice treated with rhein in combination with broad-spectrum antibiotics. We observed that the abundance of the Bacteroidetes is increased in mice treated with rhein (0.361±0.022 versus 0.185 ± 0.055, p < 0.05,). In addition, there is no significant difference in diversity between rhein-treated groups and the controls (Shannon index: p = 0.88; Simpson index: p = 0.86). Taken together, our results indicate that modulation of the gut microbiota may play an essential role in the antidiabetic effects of rhein.

scholarly journals Predictors of Effectiveness of Glucagon-Like Peptide-1 Receptor Agonist Therapy in Patients with Type 2 Diabetes and Obesity

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Alina Yu. Babenko ◽  
Daria A. Savitskaya ◽  
Yulia A. Kononova ◽  
Aleksandra Yu. Trofimova ◽  
Anna V. Simanenkova ◽  
...  
Keyword(s):  
Lipid Profile ◽  
Response To Treatment ◽  
Glucose And Lipid Metabolism ◽  
Lower Baseline ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Insulinotropic Peptide ◽  
Diabetes And Obesity ◽  
Hba1c Levels

Rationale. It is well known that diabetes mellitus (DM) exacerbates the mechanisms underlying atherosclerosis. Currently, glucagon-like peptide-1 receptor agonists (aGLP-1) have one of the most prominent cardioprotective effects among the antidiabetic agents. However, the treatment with aGLP-1 is effective only in 50-70% of the cases. Taking into account the high cost of these medications, discovery of the predictors of optimal response to treatment is required. Purpose. To identify the predictors of the greater impact of aGLP-1 on HbA1c levels, weight reduction, and improvement in lipid profile. Methods. The study group consisted of 40 patients with type 2 DM (T2DM) and obesity who were treated with aGLP-1. The follow-up period was 24 weeks. Patients’ evaluation was conducted at baseline and after 24 weeks. In addition, it included the assessment of the hormones involved in glucose and lipid metabolism and appetite regulation. Results. Patients who have initially higher BMI (body mass index), glycemia, and triglycerides (TG) had better improvement in these parameters undergoing aGLP-1 treatment. In patients with a BMI loss≥5%, GLP-1 and fasting ghrelin levels were higher and ghrelin level in postnutritional status was lower. The HbA1c levels decreased more intensively in participants with higher GLP-1 levels. TG responders had lower baseline fasting glucose-dependent insulinotropic peptide (GIP) and postprandial ghrelin levels. Conclusion. The evaluation of the glycemic control, lipid profile, and GLP-1, GIP, and ghrelin levels are useable for estimating the expected efficacy of aGLP-1.

scholarly journals Structure and dynamics of semaglutide and taspoglutide bound GLP-1R-Gs complexes

2021 ◽  
Author(s):  
Xin Zhang ◽  
Matthew J. Belousoff ◽  
Yi-Lynn Liang ◽  
Radostin Danev ◽  
Patrick M. Sexton ◽  
...  
Keyword(s):  
Structural Information ◽  
Protein Complexes ◽  
Binding Modes ◽  
Cryo Electron Microscopy ◽  
High Incidence ◽  
Molecular Determinants ◽  
Gs Protein ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Diabetes And Obesity

SUMMARYThe glucagon-like peptide-1 receptor (GLP-1R) regulates insulin secretion, carbohydrate metabolism and appetite, and is an important target for treatment of type II diabetes and obesity. Multiple GLP-1R agonists have entered into clinical trials, such as semaglutide, progressing to approval. Others, including taspoglutide, failed through high incidence of side-effects or insufficient efficacy. GLP-1R agonists have a broad spectrum of signalling profiles. However, molecular understanding is limited by a lack of structural information on how different GLP-1R agonists engage with the GLP-1R. In this study, we determined cryo-electron microscopy (cryo-EM) structures of GLP-1R-Gs protein complexes bound with semaglutide and taspoglutide. These revealed similar peptide binding modes to that previously observed for GLP-1. However, 3D variability analysis of the cryo-EM micrographs revealed different motions within the bound peptides and the receptor relative to when GLP-1 is bound. This work provides novel insights into the molecular determinants of peptide engagement with the GLP-1R.

scholarly journals Involvement of gut microbiota in association between GLP-1/GLP-1 receptor expression and gastrointestinal motility

2017 ◽  
Vol 312 (4) ◽  
pp. G367-G373 ◽  
Author(s):  
Mo Yang ◽  
Hirokazu Fukui ◽  
Hirotsugu Eda ◽  
Xin Xu ◽  
Yoshitaka Kitayama ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gastrointestinal Motility ◽  
Receptor Expression ◽  
Pivotal Role ◽  
Neural Cells ◽  
Gi Tract ◽  
Glucagon Like Peptide ◽  
Host Physiology ◽  
Glucagon Like Peptide 1 ◽  
Gi Motility

The microbiota in the gut is known to play a pivotal role in host physiology by interacting with the immune and neuroendocrine systems in gastrointestinal (GI) tissues. Glucagon-like peptide 1 (GLP-1), a gut hormone, is involved in metabolism as well as GI motility. We examined how gut microbiota affects the link between GLP-1/GLP-1 receptor (GLP-1R) expression and motility of the GI tract. Germ-free (GF) mice (6 wk old) were orally administered a fecal bacterial suspension prepared from specific pathogen-free (SPF) mice, and then after fecal transplantation (FT) GI tissues were obtained from the GF mice at various time points. The expression of GLP-1 and its receptor was examined by immunohistochemistry, and gastrointestinal transit time (GITT) was measured by administration of carmine red solution. GLP-1 was expressed in endocrine cells in the colonic mucosa, and GLP-1R was expressed in myenteric neural cells throughout the GI wall. GLP-1R-positive cells throughout the GI wall were significantly fewer in GF mice with FT than in GF mice without gut microbiota reconstitution. GITT was significantly shorter in GF mice with FT than in control GF mice without FT and correlated with the number of GLP-1R-positive cells throughout the GI wall. GITT was significantly longer in GF control mice than in SPF mice. When those mice were treated with GLP-1 agonist extendin4, GITT was significantly longer in the GF mice. The gut microbiota may accelerate or at least modify GI motility while suppressing GLP-1R expression in myenteric neural cells throughout the GI tract. NEW & NOTEWORTHY The gut microbiota has been intensively studied, because it plays a pivotal role in various aspects of host physiology. On the other hand, glucagon-like peptide 1 (GLP-1) plays important roles in metabolism as well as gastrointestinal motility. In the present study, we have suggested that the gut microbiota accelerates gastrointestinal motility while suppressing the expression of GLP-1 receptor in myenteric neural cells throughout the gastrointestinal tract. We believe that this article is very timely and suggestive work.

scholarly journals Unraveling oxyntomodulin, GLP1's enigmatic brother

2012 ◽  
Vol 215 (3) ◽  
pp. 335-346 ◽  
Author(s):  
Alessandro Pocai
Keyword(s):  
Weight Loss ◽  
Glycemic Control ◽  
Glucose Tolerance ◽  
Obese Mice ◽  
Glucagon Receptor ◽  
Glucose Levels ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Diabetes And Obesity ◽  
Dual Agonist

Oxyntomodulin (OXM) is a peptide secreted from the L cells of the gut following nutrient ingestion. OXM is a dual agonist of the glucagon-like peptide-1 receptor (GLP1R) and the glucagon receptor (GCGR) combining the effects of GLP1 and glucagon to act as a potentially more effective treatment for obesity than GLP1R agonists. Injections of OXM in humans cause a significant reduction in weight and appetite, as well as an increase in energy expenditure. Activation of GCGR is classically associated with an elevation in glucose levels, which would be deleterious in patients with T2DM, but the antidiabetic properties of GLP1R agonism would be expected to counteract this effect. Indeed, OXM administration improved glucose tolerance in diet-induced obese mice. Thus, dual agonists of the GCGR and GLP1R represent a new therapeutic approach for diabetes and obesity with the potential for enhanced weight loss and improvement in glycemic control beyond those of GLP1R agonists.

scholarly journals The effects of yam gruel on lowering fasted blood glucose in T2DM rats

2020 ◽  
Vol 15 (1) ◽  
pp. 763-773
Author(s):  
Xinjun Lin ◽  
Zongting Luo ◽  
Shuqin Pang ◽  
Carol Chunfeng Wang ◽  
Li Ge ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Gut Microbiota ◽  
Peptide Yy ◽  
Short Chain Fatty Acids ◽  
Scientific Basis ◽  
Probiotic Bacteria ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

AbstractThere is increasing evidence of the linkage between type 2 diabetes mellitus (T2DM) and gut microbiota. Based on our previous studies, we investigated the hypoglycemic mechanisms of yam gruel to provide a scientific basis for its popularization and application. Wistar rats were randomly divided into control and T2DM model groups. Rats in the model group were stimulated by a high-sugar/high-fat diet combined with an intraperitoneal injection of streptozotocin to induce T2DM. The T2DM rats were further subdivided randomly into three groups: (1) DM, (2) DM + yam gruel, and (3) DM + metformin. After 4 weeks of intervention, the changes in gut microbiota, short-chain fatty acids (SCFAs) (acetic acid, propionic acid, and butyric acid), the expression of G protein-coupled receptor 43 (GPR43), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and fasted blood glucose (FBG) levels were observed. Yam gruel intervention elevated the abundance of probiotic bacteria and increased the expression of SCFAs, GPR43 receptor, GLP-1, and PYY. It also reduced FBG levels. We conclude that yam gruel can lower FBG by promoting the growth of probiotic bacteria, increasing the content of SCFAs, and enhancing the expression of GPR43 receptor to increase the content of GLP-1 and PYY in serum.

The role of glucagon-like peptide-1 in reproduction: from physiology to therapeutic perspective

2019 ◽  
Vol 25 (4) ◽  
pp. 504-517 ◽  
Author(s):  
Mojca Jensterle ◽  
Andrej Janez ◽  
Eric Fliers ◽  
J Hans DeVries ◽  
Eda Vrtacnik-Bokal ◽  
...  
Keyword(s):  
Reproductive Health ◽  
Clinical Studies ◽  
Polycystic Ovary ◽  
Human Studies ◽  
Preclinical Models ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Diabetes And Obesity ◽  
Therapeutic Perspective

Abstract BACKGROUND Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) have become firmly established in the treatment of type 2 diabetes and obesity, disorders frequently associated with diminished reproductive health. Understanding of the role of GLP-1 and GLP-1 RAs in reproduction is currently limited and largely unaddressed in clinical studies. OBJECTIVE AND RATIONALE The purpose of this narrative review is to provide a comprehensive overview of the role of GLP-1 in reproduction and to address a therapeutic perspective that can be derived from these findings. SEARCH METHODS We performed a series of PubMed database systemic searches, last updated on 1 February 2019, supplemented by the authors’ knowledge and research experience in the field. A search algorithm was developed incorporating the terms glucagon-like peptide-1, GLP-1, glucagon-like peptide-1 receptor, GLP-1R, or incretins, and this was combined with terms related to reproductive health. The PICO (Population, Intervention, Comparison, Outcome) framework was used to identify interventional studies including GLP-1 RAs and dipeptidyl peptidase-4 (DPP-4) inhibitors, which prevent the degradation of endogenously released GLP-1. We identified 983 potentially relevant references. At the end of the screening process, we included 6 observational (3 preclinical and 3 human) studies, 24 interventional (9 preclinical and 15 human) studies, 4 case reports, and 1 systematic and 2 narrative reviews. OUTCOMES The anatomical distribution of GLP-1 receptor throughout the reproductive system and observed effects of GLP-1 in preclinical models and in a few clinical studies indicate that GLP-1 might be one of the important modulating signals connecting the reproductive and metabolic system. The outcomes show that there is mostly stimulating role of GLP-1 and its mimetics in mammalian reproduction that goes beyond mere weight reduction. In addition, GLP-1 seems to have anti-inflammatory and anti-fibrotic effects in the gonads and the endometrium affected by obesity, diabetes, and polycystic ovary syndrome (PCOS). It also seems that GLP-1 RAs and DPP-4 inhibitors can reverse polycystic ovary morphology in preclinical models and decrease serum concentrations of androgens and their bioavailability in women with PCOS. Preliminary data from interventional clinical studies suggest improved menstrual regularity as well as increased fertility rates in overweight and/or obese women with PCOS treated with GLP-1 RAs in the preconception period. WIDER IMPLICATIONS GLP-1 RAs and DPP-4 inhibitors show promise in the treatment of diabetes and obesity-related subfertility. Larger interventional studies are needed to establish the role of preconception intervention with GLP-1 based therapies, assessing fertility outcomes in obesity, PCOS, and diabetes-related fertility problems. The potential impact of the dose- and exposure time-response of different GLP-1 RAs need further exploration. Future research should also investigate sex-specific variability of GLP-1 on reproductive outcomes, in particular on the gonads where the observations in males are most conflicting.

Scaling it down: new in vitro tools to get the balance right

2016 ◽  
Vol 474 (1) ◽  
pp. 47-50 ◽  
Author(s):  
Emma K. Biggs ◽  
Fiona M. Gribble ◽  
Frank Reimann
Keyword(s):  
Bypass Surgery ◽  
Gastric Bypass Surgery ◽  
Metabolic Outcomes ◽  
Biochemical Journal ◽  
Treatment Of Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Insulinoma Cells ◽  
Diabetes And Obesity

Treatments for diabetes and obesity based on enteroendocrine hormones are a focus of research interest, partly due to the successes of glucagon-like peptide-1 (GLP-1) mimetic peptides in the treatment of diabetes and the correlation of altered enteroendocrine profiles with the positive metabolic outcomes of gastric bypass surgery. It is thought that simultaneous stimulation of more than one receptor might mimic the superior efficacy of the latter and dual or triple-agonist peptides are under investigation. An important step in developing multiple agonists is to establish the relative pharmacological potency and efficacy of new molecules at its different target receptors, and to optimise the balance of activities to achieve the desired treatment outcome. In a recent issue of the Biochemical Journal, Naylor et al. described how they used CRISPR technology to modulate endogenous receptor density in insulinoma cells to get the balance right for a dual incretin peptide engaging both GLP-1- and glucose-dependent insulinotropic polypeptide-receptors.

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