scholarly journals Effects of GLP-1 and Incretin-Based Therapies on Gastrointestinal Motor Function

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Chinmay S. Marathe ◽  
Christopher K. Rayner ◽  
Karen L. Jones ◽  
Michael Horowitz
Keyword(s):  
Inhibitory Action ◽  
Current Knowledge ◽  
Incretin Hormone ◽  
Distal Small Intestine ◽  
Gastrointestinal Motor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Antiobesity Agents ◽  
Motor Actions

Glucagon-like peptide 1 (GLP-1) is a hormone secreted predominantly by the distal small intestine and colon and released in response to enteral nutrient exposure. GLP-1-based therapies are now used widely in the management of type 2 diabetes and have the potential to be effective antiobesity agents. Although widely known as an incretin hormone, there is a growing body of evidence that GLP-1 also acts as an enterogastrone, with profound effects on the gastrointestinal motor system. Moreover, the effects of GLP-1 on gastrointestinal motility appear to be pivotal to its effect of reducing postprandial glycaemic excursions and may, potentially, represent the dominant mechanism. This review summarizes current knowledge of the enterogastrone properties of GLP-1, focusing on its effects on gut motility at physiological and pharmacological concentrations, and the motor actions of incretin-based therapies. While of potential importance, the inhibitory action of GLP-1 on gastric acid secretion is beyond the scope of this paper.

scholarly journals Glucagon-Like Peptide 1: A Predictor of Type 2 Diabetes?

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Matthias Ploug Larsen ◽  
Signe Sørensen Torekov
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Fasting Glucose ◽  
Incretin Effect ◽  
Nonesterified Fatty Acids ◽  
Incretin Hormone ◽  
Pubmed Database ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background. The incretin effect is impaired in patients with type 2 diabetes. Aim. To assess the relation between the incretin hormone GLP-1 and the prediabetic subtypes: impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and the combined IFG/IGT to investigate whether a low GLP-1 response may be a predictor of prediabetes in adults. Method. 298 articles were found using a broad search phrase on the PubMed database and after the assessment of titles and abstracts 19 articles were included. Results and Discussion. Studies assessing i-IFG/IFG and i-IGT/IGT found both increased, unaltered, and reduced GLP-1 levels. Studies assessing IFG/IGT found unaltered or reduced GLP-1 levels. When assessing the five studies with the largest sample size, it clearly suggests a decreased GLP-1 response in IFG/IGT subjects. Several other factors (BMI, glucagon, age, and nonesterified fatty acids (NEFA)), including medications (metformin), may also influence the secretion of GLP-1. Conclusion. This review suggests that the GLP-1 response is a variable in prediabetes possibly due to a varying GLP-1-secreting profile during the development and progression of type 2 diabetes or difference in the measurement technique. Longitudinal prospective studies are needed to assess whether a reduced GLP-1 response is a predictor of diabetes.

scholarly journals PYY, a Therapeutic Option for Type 2 Diabetes?

2020 ◽  
Vol 13 ◽  
pp. 117955141989298 ◽  
Author(s):  
Claudia Guida ◽  
Reshma Ramracheya
Keyword(s):  
Current Knowledge ◽  
Therapeutic Option ◽  
Gut Hormones ◽  
Islet Function ◽  
Appetite Regulation ◽  
Treatment Of Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Lines Of Evidence

Metabolic surgery leads to rapid and effective diabetes reversal in humans, by weight-independent mechanisms. The crucial improvement in pancreatic islet function observed after surgery is induced by alteration in several factors, including gut hormones. In addition to glucagon-like peptide 1 (GLP-1), increasing lines of evidence show that peptide tyrosine tyrosine (PYY) plays a key role in the metabolic benefits associated with the surgery, ranging from appetite regulation to amelioration of islet secretory properties and survival. Here, we summarize the current knowledge and the latest advancements in the field, which pitch a strong case for the development of novel PYY-based therapy for the treatment of diabetes.

Bile-induced secretion of glucagon-like peptide-1: pathophysiological implications in type 2 diabetes?

2010 ◽  
Vol 299 (1) ◽  
pp. E10-E13 ◽  
Author(s):  
Filip K. Knop
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Intestinal Secretion ◽  
Postprandial Glucose ◽  
Glucose Lowering ◽  
Incretin Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

During the last decades it has become clear that bile acids not only act as simple fat solubilizers, but additionally represent complex hormonal metabolic integrators. Bile acids activate both nuclear receptors (controlling transcription of genes involved in for example bile acid, cholesterol, and glucose metabolism) and the cell surface G protein-coupled receptor TGR5 (modulating energy expenditure in brown fat and muscle cells). It has been shown that TGR5 is expressed in enteroendocrine L cells, which secrete the potent glucose-lowering incretin hormone glucagon-like peptide-1 (GLP-1). Recently it was shown that bile acid-induced activation of TGR5 results in intestinal secretion of GLP-1 and that enhanced TGR5 signaling improves postprandial glucose tolerance in diet-induced obese mice. This Perspectives article presents these novel findings in the context of prior studies on nutrient-induced GLP-1 secretion and outlines the potential implications of bile acid-induced GLP-1 secretion in physiological, pathophysiological, and pharmacological perspectives.

RANTES (CCL5) reduces glucose-dependent secretion of glucagon-like peptides 1 and 2 and impairs glucose-induced insulin secretion in mice

2014 ◽  
Vol 307 (3) ◽  
pp. G330-G337 ◽  
Author(s):  
Ramona Pais ◽  
Tamara Zietek ◽  
Hans Hauner ◽  
Hannelore Daniel ◽  
Thomas Skurk
Keyword(s):  
Insulin Secretion ◽  
Glucose Transporter ◽  
Cell Loss ◽  
Oral Glucose ◽  
Diabetes Therapy ◽  
Incretin Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Type 2 diabetes is associated with elevated circulating levels of the chemokine RANTES and with decreased plasma levels of the incretin hormone glucagon-like peptide 1 (GLP-1). GLP-1 is a peptide secreted from intestinal L-cells upon nutrient ingestion. It enhances insulin secretion from pancreatic β-cells and protects from β-cell loss but also promotes satiety and weight loss. In search of chemokines that may reduce GLP-1 secretion we identified RANTES and show that it reduces glucose-stimulated GLP-1 secretion in the human enteroendocrine cell line NCI-H716, blocked by the antagonist Met-RANTES, and in vivo in mice. RANTES exposure to mouse intestinal tissues lowers transport function of the intestinal glucose transporter SGLT1, and administration in mice reduces plasma GLP-1 and GLP-2 levels after an oral glucose load and thereby impairs insulin secretion. These data show that RANTES is involved in altered secretion of glucagon-like peptide hormones most probably acting through SGLT1, and our study identifies the RANTES-receptor CCR1 as a potential target in diabetes therapy.

scholarly journals Glucose-dependent insulinotropic polypeptide - a new link in the development of obesity

2015 ◽  
Vol 12 (1) ◽  
pp. 16-19 ◽  
Author(s):  
Ekaterina Alekseevna Shestakova ◽  
Aleksandr Victorovich Il'in ◽  
Marina Vladimirovna Shestakova ◽  
Ivan Ivanovich Dedov
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Insulin Secretion ◽  
Lipid Metabolism ◽  
Body Mass ◽  
Incretin Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Objective. Glucose-dependent insulinotropic polypeptide (GIP) as well as glucagon-like peptide-1 (GLP-1) is intestinal incretin hormone that stimulates insulin secretion in response to feeding. Much evidence of GIP contribution to obesity development has been found recently.Aim. The aim of the study was to evaluate glucose-stimulated GIP and GLP-1 secretion in people with type 2 diabetes (T2D) risk factors and different body mass index (BMI).Materials and methods. Total GIP and GLP-1 secretion was estimated in 127 patients with T2D risk factors during OGTT (75 g glucose) on 0, 30 and 120 minutes.Results. Patients with BMI≥ 35 kg/m2 had significantly higher fasting and stimulated GIP levels than participants with less BMI. GIP secretion was also higher in patients was insulinresistance, estimated by HOMA-IR, comparing to non-insulinresistant patients. Difference in GLP-1 secretion in patients within several BMI groups was nonsignificant.Conclusion. Our results suggest GIP is related to obesity degree, that means it can play a role in lipid metabolism and obesity development. 

scholarly journals Minireview: Update on Incretin Biology: Focus on Glucagon-Like Peptide-1

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 1984-1989 ◽  
Author(s):  
Patricia L. Brubaker
Keyword(s):  
Molecular Medicine ◽  
Immunomodulatory Effects ◽  
Β Cell ◽  
Incretin Hormone ◽  
Therapeutic Modalities ◽  
Reduce Body Weight ◽  
Fundamental Biology ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The incretin hormone, glucagon-like peptide-1 (GLP-1), is now being used in the clinic to enhance insulin secretion and reduce body weight in patients with type 2 diabetes. Although much is already known about the biology of GLP-1, much remains to be understood. Hence, this review will consider recent findings related to the potential for enhancing endogenous levels of GLP-1 through selective use of secretagogues and the beneficial cardiovascular, neuroprotective, and immunomodulatory effects of GLP-1, as well as the possible effects of GLP-1 to enhance β-cell growth and/or to induce pancreatitis or thyroid cancer. Finally, the potential for molecular medicine to enhance the success of GLP-1 therapy in the clinic is considered. A better understanding of the fundamental biology of GLP-1 may lead to new therapeutic modalities for the clinical use of this intestinal hormone.

scholarly journals A sandwich ELISA for measurement of the primary glucagon-like peptide-1 metabolite

2017 ◽  
Vol 313 (3) ◽  
pp. E284-E291 ◽  
Author(s):  
Nicolai J. Wewer Albrechtsen ◽  
Ali Asmar ◽  
Frederik Jensen ◽  
Signe Törang ◽  
Lene Simonsen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Sandwich Elisa ◽  
Active Form ◽  
Primary Metabolite ◽  
Incretin Hormone ◽  
Dipeptidyl Peptidase 4 ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from the gastrointestinal tract. It is best known for its glucose-dependent insulinotropic effects. GLP-1 is secreted in its intact (active) form (7–36NH2) but is rapidly degraded by the dipeptidyl peptidase 4 (DPP-4) enzyme, converting >90% to the primary metabolite (9–36NH2) before reaching the targets via the circulation. Although originally thought to be inactive or antagonistic, GLP-1 9–36NH2 may have independent actions, and it is therefore relevant to be able to measure it. Because reliable assays were not available, we developed a sandwich ELISA recognizing both GLP-1 9–36NH2 and nonamidated GLP-1 9–37. The ELISA was validated using analytical assay validation guidelines and by comparing it to a subtraction-based method, hitherto employed for estimation of GLP-1 9–36NH2. Its accuracy was evaluated from measurements of plasma obtained during intravenous infusions (1.5 pmol × kg−1 × min−1) of GLP-1 7–36NH2 in healthy subjects and patients with type 2 diabetes. Plasma levels of the endogenous GLP-1 metabolite increased during a meal challenge in patients with type 2 diabetes, and treatment with a DPP-4 inhibitor fully blocked its formation. Accurate measurements of the GLP-1 metabolite may contribute to understanding its physiology and role of GLP-1 in diabetes.

scholarly journals The Vildagliptin Experience – 25 Years Since the Initiation of the Novartis Glucagon-like Peptide-1 Based Therapy Programme and 10 Years Since the First Vildagliptin Registration

2017 ◽  
Vol 13 (02) ◽  
pp. 56 ◽  
Author(s):  
James E Foley ◽  
Bo Ahrén ◽  
◽  
Keyword(s):  
Glycaemic Control ◽  
Mechanism Of Action ◽  
Incretin Hormone ◽  
Dipeptidyl Peptidase 4 ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Improved Glycaemic Control ◽  
Kinetics Of ◽  
Therapy Programme

The discovery of the incretin hormone glucagon like peptide-1 (GLP-1), and its usefulness in the treatment of type 2 diabetes mellitus (T2DM) followed by the finding that dipeptidyl peptidase-4 (DPP-4) inhibition prevents GLP-1 inactivation, led to the discovery of DPP-728. In 1999, studies with DPP-728 established the first proof-of-concept that DPP-4 inhibition improves glycaemic control in patients with T2DM. Further efforts to improve the binding kinetics of DPP-728 resulted in the discovery of vildagliptin (LAF237). In the last 20 years, a plethora of studies conducted by Novartis in collaboration with external investigators has demonstrated the mechanism of action of vildagliptin and its efficacy as monotherapy and as an add-on therapy for patients with T2DM. The studies establish that vildagliptin is a selective DPP-4 inhibitor that blocks GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) inactivation, thereby prolonging their action, resulting in improved glycaemic control. This review aims to discuss the discovery and development of vildagliptin, with an emphasis on mechanism of action and clinical efficacy.

Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2

1999 ◽  
Vol 276 (5) ◽  
pp. R1541-R1544 ◽  
Author(s):  
Jean-Pierre Gutzwiller ◽  
Jürgen Drewe ◽  
Burkhard Göke ◽  
Harald Schmidt ◽  
Beat Rohrer ◽  
...  
Keyword(s):  
Energy Intake ◽  
Diabetes Type 2 ◽  
Diabetes Type ◽  
Double Blind ◽  
Incretin Hormone ◽  
Visual Analog Scales ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1-(7—36) amide (GLP-1) is an incretin hormone of the enteroinsular axis. Recent experimental evidence in animals and healthy subjects suggests that GLP-1 has a role in controlling appetite and energy intake in humans. We have therefore examined in a double-blind, placebo-controlled, crossover study in 12 patients with diabetes type 2 the effect of intravenously infused GLP-1 on appetite sensations and energy intake. On 2 days, either saline or GLP-1 (1.5 pmol ⋅ kg−1 ⋅ min−1) was given throughout the experiment. Visual analog scales were used to assess appetite sensations; furthermore, food and fluid intake of a test meal were recorded, and blood was sampled for analysis of plasma glucose and hormone levels. GLP-1 infusion enhanced satiety and fullness compared with placebo ( P = 0.028 for fullness and P = 0.026 for hunger feelings). Energy intake was reduced by 27% by GLP-1 ( P = 0.034) compared with saline. The results demonstrate a marked effect of GLP-1 on appetite by showing enhanced satiety and reduced energy intake in patients with diabetes type 2.

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