ABSTRACT
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are two incretins that bind to their respective receptors and activate the downstream signaling in various tissues and organs. Both GIP and GLP-1 play roles in regulating food intake by stimulating neurons in the brain's satiety center. They also stimulate insulin secretion in pancreatic ß-cells, but their effects on glucagon production in pancreatic α-cells differ, with GIP having a glucagonotropic effect during hypoglycemia and GLP-1 exhibiting glucagonostatic effect during hyperglycemia. Additionally, GIP directly stimulates lipogenesis, while GLP-1 indirectly promotes lipolysis, collectively maintaining healthy adipocytes, reducing ectopic fat distribution, and increasing the production and secretion of adiponectin from adipocytes. Together, these two incretins contribute to metabolic homeostasis, preventing both hyperglycemia and hypoglycemia, mitigating dyslipidemia, and reducing the risk of cardiovascular diseases in individuals with type 2 diabetes and obesity. Several GLP-1 and dual GIP/GLP-1 receptor agonists have been developed to harness these pharmacological effects in the treatment of type 2 diabetes, with some demonstrating robust effectiveness in weight management and prevention of cardiovascular diseases. Elucidating the underlying cellular and molecular mechanisms could potentially usher in the development of new generations of incretin mimetics with enhanced efficacy and fewer adverse effects. The treatment guidelines are evolving based on clinical trial outcomes, shaping the management of metabolic and cardiovascular diseases.
Subject(s)
Diabetes Mellitus, Type 2 , Gastric Inhibitory Polypeptide , Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor Agonists , Receptors, Gastrointestinal Hormone , Animals , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Gastric Inhibitory Polypeptide/therapeutic use , Glucagon-Like Peptide 1/metabolism , Glucagon-Like Peptide 1/agonists , Glucagon-Like Peptide-1 Receptor Agonists/pharmacology , Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/pharmacology , Incretins/therapeutic use , Incretins/pharmacology , Receptors, Gastrointestinal Hormone/agonists , Receptors, Gastrointestinal Hormone/metabolismSubject(s)
Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor , Obesity , Humans , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide 1/agonists , Obesity/drug therapy , Gastric Inhibitory Polypeptide/therapeutic use , Receptors, Gastrointestinal Hormone/agonists , Anti-Obesity Agents/adverse effects , Anti-Obesity Agents/therapeutic use , Anti-Obesity Agents/administration & dosage , Weight Loss/drug effects , Animals , Glucagon-Like Peptide-1 Receptor AgonistsSubject(s)
Diabetes Mellitus, Type 2 , Gastric Inhibitory Polypeptide , Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor , Hypoglycemic Agents , Humans , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide 1/agonists , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacology , Gastric Inhibitory Polypeptide/therapeutic use , Receptors, Gastrointestinal Hormone/agonists , Animals , Glucagon-Like Peptide-1 Receptor AgonistsABSTRACT
Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an α2-adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABAA receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS.
Subject(s)
Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor , Insulin Secretion , Mice, Inbred C57BL , Olfactory Bulb , Paraventricular Hypothalamic Nucleus , Animals , Glucagon-Like Peptide 1/metabolism , Male , Olfactory Bulb/metabolism , Olfactory Bulb/drug effects , Insulin Secretion/drug effects , Glucagon-Like Peptide-1 Receptor/metabolism , Mice , Paraventricular Hypothalamic Nucleus/metabolism , Insulin/metabolism , Obesity/metabolism , Sympathetic Nervous System/metabolism , Neurons/metabolism , Signal Transduction , Norepinephrine/metabolism , Glucose/metabolismABSTRACT
Glucagon-like peptide 1 (GLP1), which is mainly processed and cleaved from proglucagon in enteroendocrine cells (EECs) of the intestinal tract, acts on the GLP1 receptor in pancreatic cells to stimulate insulin secretion and to inhibit glucagon secretion. However, GLP1 processing is not fully understood. Here, we show that reticulon 4B (Nogo-B), an endoplasmic reticulum (ER)-resident protein, interacts with the major proglucagon fragment of proglucagon to retain proglucagon on the ER, thereby inhibiting PCSK1-mediated cleavage of proglucagon in the Golgi. Intestinal Nogo-B knockout in male type 2 diabetes mellitus (T2DM) mice increases GLP1 and insulin levels and decreases glucagon levels, thereby alleviating pancreatic injury and insulin resistance. Finally, we identify aberrantly elevated Nogo-B expression and inhibited proglucagon cleavage in EECs from diabetic patients. Our study reveals the subcellular regulatory processes involving Nogo-B during GLP1 production and suggests intestinal Nogo-B as a potential therapeutic target for T2DM.
Subject(s)
Diabetes Mellitus, Type 2 , Endoplasmic Reticulum , Glucagon-Like Peptide 1 , Nogo Proteins , Proglucagon , Proprotein Convertase 1 , Animals , Humans , Male , Mice , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/genetics , Endoplasmic Reticulum/metabolism , Enteroendocrine Cells/metabolism , Glucagon-Like Peptide 1/metabolism , Golgi Apparatus/metabolism , HEK293 Cells , Insulin/metabolism , Insulin Resistance , Intestines/pathology , Mice, Inbred C57BL , Mice, Knockout , Nogo Proteins/metabolism , Nogo Proteins/genetics , Proglucagon/metabolism , Proglucagon/genetics , Proprotein Convertase 1/metabolism , Proprotein Convertase 1/genetics , Protein Binding , ProteolysisABSTRACT
Derived from enteroendocrine cells (EECs), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are pivotal incretin hormones crucial for blood glucose regulation. Medications of GLP-1 analogs and GLP-1 receptor activators are extensively used in the treatment of type 2 diabetes (T2D) and obesity. However, there are currently no agents to stimulate endogenous incretin secretion. Here, we find the pivotal role of KCNH2 potassium channels in the regulation of incretin secretion. Co-localization of KCNH2 with incretin-secreting EECs in the intestinal epithelium of rodents highlights its significance. Gut epithelial cell-specific KCNH2 knockout in mice improves glucose tolerance and increases oral glucose-triggered GLP-1 and GIP secretion, particularly GIP. Furthermore, KCNH2-deficient primary intestinal epithelial cells exhibit heightened incretin, especially GIP secretion upon nutrient stimulation. Mechanistically, KCNH2 knockdown in EECs leads to reduced K+ currents, prolonged action potential duration, and elevated intracellular calcium levels. Finally, we found that dofetilide, a KCNH2-specific inhibitor, could promote incretin secretion in enteroendocrine STC-1 cells in vitro and in hyperglycemic mice in vivo. These findings elucidate, for the first time, the mechanism and application of KCNH2 in regulating incretin secretion by EECs. Given the therapeutic promise of GLP-1 and GIP in diabetes and obesity management, this study advances our understanding of incretin regulation, paving the way for potential incretin secretagogue therapies in the treatment of diabetes and obesity.
Subject(s)
Enteroendocrine Cells , Glucagon-Like Peptide 1 , Incretins , Animals , Mice , Incretins/pharmacology , Enteroendocrine Cells/metabolism , Enteroendocrine Cells/drug effects , Glucagon-Like Peptide 1/genetics , Glucagon-Like Peptide 1/metabolism , Humans , Gastric Inhibitory Polypeptide/genetics , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/pathology , Secretagogues/pharmacology , Mice, Knockout , ERG1 Potassium ChannelABSTRACT
ABSTRACT: In the last decade, the glucagon-like peptide-1 (GLP-1) receptor agonist (RA) drug class has revolutionized treatment for type 2 diabetes mellitus and some of its comorbidities, including obesity and cardiovascular disease. Continued advancements in the GLP-1 RA space show clinical promise for patients, though challenges-including barriers to care such as drug expense and availability-exist. This article provides an overview of available GLP-1 RAs and their mechanisms of action, indications, adverse reactions, and risks, providing practical pearls for providers along the way.
Subject(s)
Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Hypoglycemic Agents , Humans , Glucagon-Like Peptide-1 Receptor/agonists , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Glucagon-Like Peptide 1/agonists , Glucagon-Like Peptide 1/metabolismSubject(s)
Glucagon-Like Peptide 1 , Neuroprotective Agents , Signal Transduction , Humans , Glucagon-Like Peptide 1/metabolism , Signal Transduction/physiology , Animals , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/pharmacology , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/metabolism , Nervous System/metabolism , Neuroprotection/physiologyABSTRACT
In recent years, there has been a gradual increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM), with bariatric surgery remaining the most effective treatment strategy for these conditions. Vertical sleeve gastrectomy (VSG) has emerged as the most popular surgical procedure for bariatric/metabolic surgeries, effectively promoting weight loss and improving or curing T2DM. The alterations in the gastrointestinal tract following VSG may improve insulin secretion and resistance by increasing incretin secretion (especially GLP-1), modifying the gut microbiota composition, and through mechanisms dependent on weight loss. This review focuses on the potential mechanisms through which the enhanced action of incretin and metabolic changes in the digestive system after VSG may contribute to the remission of T2DM.
Subject(s)
Diabetes Mellitus, Type 2 , Gastrectomy , Obesity, Morbid , Weight Loss , Humans , Diabetes Mellitus, Type 2/surgery , Gastrectomy/methods , Obesity, Morbid/surgery , Remission Induction , Incretins , Gastrointestinal Microbiome , Bariatric Surgery/methods , Treatment Outcome , Insulin Resistance , Glucagon-Like Peptide 1/metabolismABSTRACT
The escalating global prevalence of type-2 diabetes (T2D) and obesity necessitates the development of novel oral medications. Agonism at G-protein coupled receptor-119 (GPR119) has been recognized for modulation of metabolic homeostasis in T2D, obesity, and fatty liver disease. However, off-target effects have impeded the advancement of synthetic GPR119 agonist drug candidates. Non-systemic, gut-restricted GPR119 agonism is suggested as an alternative strategy that may locally stimulate intestinal enteroendocrine cells (EEC) for incretin secretion, without the need for systemic drug availability, consequently alleviating conventional class-related side effects. Herein, we report the preclinical acute safety, efficacy, and pharmacokinetics (PK) of novel GPR119 agonist compounds ps297 and ps318 that potentially target gut EEC for incretin secretion. In a proof-of-efficacy study, both compounds demonstrated glucagon-like peptide-1 (GLP-1) secretion capability during glucose and mixed-meal tolerance tests in healthy mice. Furthermore, co-administration of sitagliptin with investigational compounds in diabetic db/db mice resulted in synergism, with GLP-1 concentrations rising by three-fold. Both ps297 and ps318 exhibited low gut permeability assessed in the in-vitro Caco-2 cell model. A single oral dose PK study conducted on healthy mice demonstrated poor systemic bioavailability of both agents. PK measures (mean ± SD) for compound ps297 (Cmax 23 ± 19â¯ng/mL, Tmax range 0.5 - 1â¯h, AUC0-24â¯h 19.6 ± 21â¯h*ng/mL) and ps318 (Cmax 75 ± 22â¯ng/mL, Tmax range 0.25 - 0.5â¯h, AUC0-24â¯h 35 ± 23â¯h*ng/mL) suggest poor oral absorption. Additionally, examinations of drug excretion patterns in mice revealed that around 25â¯% (ps297) and 4â¯% (ps318) of the drugs were excreted through faeces as an unchanged form, while negligible drug concentrations (<0.005â¯%) were excreted in the urine. These acute PK/PD assessments suggest the gut is a primary site of action for both agents. Toxicity assessments conducted in the zebrafish and healthy mice models confirmed the safety and tolerability of both compounds. Future chronic in-vivo studies in relevant disease models will be essential to confirm the long-term safety and efficacy of these novel compounds.
Subject(s)
Diabetes Mellitus, Type 2 , Obesity , Receptors, G-Protein-Coupled , Animals , Humans , Male , Mice , Caco-2 Cells , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Enteroendocrine Cells/drug effects , Enteroendocrine Cells/metabolism , Glucagon-Like Peptide 1/metabolism , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/pharmacology , Mice, Inbred C57BL , Obesity/drug therapy , Obesity/metabolism , Receptors, G-Protein-Coupled/agonists , Receptors, G-Protein-Coupled/metabolismABSTRACT
For more than a century, physicians have searched for ways to pharmacologically reduce excess body fat. The tide has finally turned with recent advances in biochemically engineered agonists for the receptor of glucagon-like peptide-1 (GLP-1) and their use in GLP-1-based polyagonists. These polyagonists reduce body weight through complementary pharmacology by incorporating the receptors for glucagon and/or the glucose-dependent insulinotropic polypeptide (GIP). In their most advanced forms, gut-hormone polyagonists achieve an unprecedented weight reduction of up to â¼20%-30%, offering a pharmacological alternative to bariatric surgery. Along with favorable effects on glycemia, fatty liver, and kidney disease, they also offer beneficial effects on the cardiovascular system and adipose tissue. These new interventions, therefore, hold great promise for the future of anti-obesity medications.
Subject(s)
Anti-Obesity Agents , Obesity , Humans , Obesity/drug therapy , Obesity/metabolism , Anti-Obesity Agents/therapeutic use , Anti-Obesity Agents/pharmacology , Animals , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/metabolism , Glucagon-Like Peptide 1/metabolism , Adipose Tissue/metabolism , Adipose Tissue/drug effectsABSTRACT
Baltic herring is the main catch in the Baltic Sea; however, its usage could be improved due to the low processing rate. Previously we have shown that whole Baltic herring hydrolysates (BHH) and herring byproducts hydrolysates (BHBH) by commercial enzymes consisted of bioactive peptides and had moderate bioactivity in in vitro dipeptidyl peptidase (DPP)-4 assay. In this study, we identified the hydrolysate peptides by LC-MS/MS and predicted the potential bioactive DPP-4 inhibitory peptides using in silico tools. Based on abundance, peptide length and stability, 86 peptides from BHBH and 80 peptides from BHH were proposed to be novel DPP-4 inhibitory peptides. BHH was fed to a mice intervention of a high-fat, high-fructose diet to validate the bioactivity. The results of the glucose tolerance and insulin tolerance improved. Plasma DPP-4 activities, C-peptide levels, and HOMA-IR scores significantly decreased, while plasma glucagon-like peptide-1 content increased. In conclusion, BHH is an inexpensive and sustainable source of functional antidiabetic ingredients.
Subject(s)
Dipeptidyl Peptidase 4 , Dipeptidyl-Peptidase IV Inhibitors , Obesity , Animals , Dipeptidyl Peptidase 4/metabolism , Mice , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Obesity/metabolism , Male , Peptides , Diet, High-Fat , Fishes , Protein Hydrolysates/pharmacology , Protein Hydrolysates/chemistry , Disease Models, Animal , Tandem Mass Spectrometry , Hypoglycemic Agents/pharmacology , Computer Simulation , Mice, Inbred C57BL , Blood Glucose/metabolism , Blood Glucose/drug effects , Glucagon-Like Peptide 1/metabolism , Insulin ResistanceABSTRACT
(1) Background: Proglucagon-derived peptides (PDGPs) including glucagon (Gcg), GLP-1, and GLP-2 regulate lipid metabolism in the liver, adipocytes, and intestine. However, the mechanism by which PGDPs participate in alterations in lipid metabolism induced by high-fat diet (HFD) feeding has not been elucidated. (2) Methods: Mice deficient in PGDP (GCGKO) and control mice were fed HFD for 7 days and analyzed, and differences in lipid metabolism in the liver, adipose tissue, and duodenum were investigated. (3) Results: GCGKO mice under HFD showed lower expression levels of the genes involved in free fatty acid (FFA) oxidation such as Hsl, Atgl, Cpt1a, Acox1 (p < 0.05), and Pparα (p = 0.05) mRNA in the liver than in control mice, and both FFA and triglycerides content in liver and adipose tissue weight were lower in the GCGKO mice. On the other hand, phosphorylation of hormone-sensitive lipase (HSL) in white adipose tissue did not differ between the two groups. GCGKO mice under HFD exhibited lower expression levels of Pparα and Cd36 mRNA in the duodenum as well as increased fecal cholesterol contents compared to HFD-controls. (4) Conclusions: GCGKO mice fed HFD exhibit a lesser increase in hepatic FFA and triglyceride contents and adipose tissue weight, despite reduced ß-oxidation in the liver, than in control mice. Thus, the absence of PGDP prevents dietary-induced fatty liver development due to decreased lipid uptake in the intestinal tract.
Subject(s)
CD36 Antigens , Diet, High-Fat , Intestinal Absorption , Lipid Metabolism , Liver , Mice, Knockout , PPAR alpha , Proglucagon , Animals , Male , Diet, High-Fat/adverse effects , PPAR alpha/metabolism , PPAR alpha/genetics , Liver/metabolism , Proglucagon/metabolism , Proglucagon/genetics , CD36 Antigens/metabolism , CD36 Antigens/genetics , Mice , Sterol Esterase/metabolism , Sterol Esterase/genetics , Triglycerides/metabolism , Mice, Inbred C57BL , Fatty Acids, Nonesterified/metabolism , Glucagon-Like Peptide 1/metabolism , Duodenum/metabolism , Carnitine O-Palmitoyltransferase/metabolism , Carnitine O-Palmitoyltransferase/genetics , Adipose Tissue/metabolism , Dietary Fats , Glucagon-Like Peptide 2/metabolism , Acyltransferases , LipaseABSTRACT
Glucagon-like peptide-1 (GLP-1) and N-methyl-D-aspartate (NMDA) receptors in the brain regulate metabolic homeostasis. In a paper published in Nature, Petersen et al. describe a bimodal molecule that conjugates a GLP-1 analog with MK-801 (NMDA receptor antagonist), which lowers feeding and body weight to a greater extent than the GLP-1R agonist alone.
Subject(s)
Brain , Glucagon-Like Peptide 1 , Receptors, N-Methyl-D-Aspartate , Receptors, N-Methyl-D-Aspartate/metabolism , Glucagon-Like Peptide 1/metabolism , Brain/metabolism , Animals , Humans , Dizocilpine Maleate/pharmacology , Glucagon-Like Peptide-1 Receptor/metabolism , Glucagon-Like Peptide-1 Receptor/agonistsABSTRACT
BACKGROUND: This study aimed to investigate the impact of Vitamin A (VA) on intestinal glucose metabolic phenotypes. METHODS: Male C57BL/6 mice were randomized assigned to a VA-normal diet (VAN) or a VA-deficient diet (VAD) for 12 weeks. After12 weeks, the VAD mice were given 30 IU/g/d retinol for 10 days and VAN diet (VADN) for 10 weeks. By using glucose tolerance tests, immunofluorescence staining, quantitative polymerase chain reaction, siRNA transduction, and enzyme-linked immunosorbent assay, the glucose metabolic phenotypes as well as secretory function and intracellular hormone changes of STC-1 were assessed. RESULTS: VAD mice showed a decrease of glucose-stimulated insulin secretion and a loss of intestinal glucagon-like peptide-1 (GLP-1) expression. Through reintroducing dietary VA to VAD mice, the intestinal VA levels, GLP-1 expression and normal glucose can be restored. The incubation with retinol increased VA signaling factors expression within STC-1 cells, especially retinoic acid receptor ß (RARß). The activation of RARß restored intracellular incretin hormone synthesis and secretory function. CONCLUSIONS: VA deficiency leads to an imbalance of intestinal glucose metabolic phenotypes through a mechanism involving RARß signaling pathway, suggesting a new method to achieve the treatment for VAD induced glucose metabolism impairment.
Subject(s)
Glucagon-Like Peptide 1 , Incretins , Mice, Inbred C57BL , Receptors, Retinoic Acid , Vitamin A , Animals , Male , Vitamin A/metabolism , Mice , Receptors, Retinoic Acid/metabolism , Receptors, Retinoic Acid/genetics , Incretins/metabolism , Glucagon-Like Peptide 1/metabolism , Vitamin A Deficiency/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Signal Transduction/drug effects , Insulin Secretion/drug effects , Insulin Secretion/physiologyABSTRACT
Konjac glucomannan (KGM), high-viscosity dietary fiber, is utilized in weight management. Previous investigations on the appetite-suppressing effects of KGM have centered on intestinal responses to nutrients and gastric emptying rates, with less focus on downstream hypothalamic neurons of satiety hormones. In our studies, the molecular mechanisms through which KGM and its degradation products influence energy homeostasis via the adipocyte-hypothalamic axis have been examined. It was found that high-viscosity KGM more effectively stimulates enteroendocrine cells to release glucagon-like peptide-1 (GLP-1) and reduces ghrelin production, thereby activating hypothalamic neurons and moderating short-term satiety. Conversely, low-viscosity DKGM has been shown to exhibit stronger anti-inflammatory properties in the hypothalamus, enhancing hormone sensitivity and lowering the satiety threshold. Notably, both KGM and DKGM significantly reduced leptin signaling and fatty acid signaling in adipose tissue and activated brown adipose tissue thermogenesis to suppress pro-opiomelanocortin (POMC) expression and activate agouti-related protein (AgRP) expression, thereby reducing food intake and increasing energy expenditure. Additionally, high-viscosity KGM has been found to activate the adipocyte-hypothalamus axis more effectively than DKGM, thereby promoting greater daily energy expenditure. These findings provide novel insights into the adipocyte-hypothalamic axis for KGM to suppress appetite and reduce weight.
Subject(s)
Adipocytes , Appetite Regulation , Diet, High-Fat , Energy Metabolism , Hypothalamus , Mice, Inbred C57BL , Animals , Mice , Energy Metabolism/drug effects , Hypothalamus/metabolism , Hypothalamus/drug effects , Diet, High-Fat/adverse effects , Male , Appetite Regulation/drug effects , Adipocytes/metabolism , Adipocytes/drug effects , Humans , Glucagon-Like Peptide 1/metabolism , Ghrelin/metabolism , Leptin/metabolism , Agouti-Related Protein/metabolism , Agouti-Related Protein/genetics , Thermogenesis/drug effects , Pro-Opiomelanocortin/metabolism , Pro-Opiomelanocortin/genetics , Obesity/metabolism , Obesity/physiopathology , Obesity/diet therapy , MannansABSTRACT
BACKGROUND: The differential effects of pecans versus other popular snack foods on appetite and blood markers of metabolism and satiety have not been well studied. This study investigated the effects of a single mid-morning snack of pecans or tortilla chips on subjective appetite, food intake, blood measures of hormones and metabolites, and resting energy expenditure. METHODS: Twenty participants with overweight and obesity were enrolled in a within-participants, randomized crossover trial. Participants had indwelling catheters placed for blood sampling and were fed a standardized breakfast, followed two hours later by a 250 kcal snack of either pecans or tortilla chips, and then by a self-selected lunch. Visual analog scale (VAS) appetite measures, blood markers, and energy expenditure were taken at intervals after food consumption. RESULTS: VAS ratings, energy, food intake and macronutrient composition did not differ between treatment conditions, but glucose and insulin were significantly more elevated after tortilla chips. Free fatty acids (FFA), triglycerides (TG), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) were higher after consuming pecans compared to tortilla chips. CONCLUSIONS: Pecan consumption improves postprandial glucose and insulin profiles which would be beneficial to individuals at risk of developing type 2 diabetes. Further studies are needed to investigate whether increased relative secretion of PYY and GLP-1 after eating pecans versus tortilla chips may affect subjective appetite and energy intake if consumed chronically.
Subject(s)
Appetite , Biomarkers , Cross-Over Studies , Energy Metabolism , Insulin , Obesity , Overweight , Snacks , Humans , Male , Female , Adult , Obesity/blood , Biomarkers/blood , Overweight/blood , Insulin/blood , Blood Glucose/metabolism , Glucagon-Like Peptide 1/blood , Middle Aged , Healthy Volunteers , Eating/physiology , Energy Intake , Dietary Carbohydrates/administration & dosage , Peptide YY/blood , Postprandial Period , Young AdultABSTRACT
Glucagon-like Peptide-1 (GLP-1) receptor agonists (GLP-1RAs) emerged as a primary treatment for type-2 diabetes mellitus (T2DM), however, their multifaceted effects on various target organs beyond glycemic control opened a new era of treatment. We conducted a comprehensive literature search using databases including Scopus, Google Scholar, PubMed, and the Cochrane Library to identify clinical, in-vivo, and in-vitro studies focusing on the diverse effects of GLP-1 receptor agonists. Eligible studies were selected based on their relevance to the varied roles of GLP-1RAs in T2DM management and their impact on other physiological functions. Numerous studies have reported the efficacy of GLP-1RAs in improving outcomes in T2DM, with demonstrated benefits including glucose-dependent insulinotropic actions, modulation of insulin signaling pathways, and reductions in glycemic excursions. Additionally, GLP-1 receptors are expressed in various tissues and organs, suggesting their widespread physiological functions beyond glycemic control potentially include neuroprotective, anti-inflammatory, cardioprotective, and metabolic benefits. However, further scientific studies are still underway to maximize the benefits of GLP-1RAs and to discover additional roles in improving health benefits. This article sought to review not only the actions of GLP1RAs in the treatment of T2DM but also explore its effects on potential targets in other disorders.