GPR119 in Neurometabolic Control and Therapeutic Development
College
College of Arts and Sciences
Mentor Information
Dr. Stuart Maudsley PhD
Description
GPR-119 is a G protein-coupled receptor expressed in pancreatic beta cells and intestinal endocrine cells. Activation of GPR-119 through agonists has been studied for therapeutic developments, as it plays roles in glucose homeostasis, regulation of chronic inflammation, and appetite control. GPR-119 modulators can increase incretin secretion (GLP-1), without direct stimulation of insulin release—leading to enhanced glucose control, appetite reduction, and anti-inflammatory effects. Previous studies have highlighted gut-restricted agonists’ effectiveness in patients with metabolic diseases. This study aims to determine whether activation of restricted GPR-119 agonists affects body weight regulation, insulin secretion, and inflammation in patients with metabolic diseases compared to healthy patients. A literature review was conducted to evaluate the role of GPR-119 in metabolic pathways. A PubMed search utilizing “GPR-119” yielded 92 articles published across a 5-year period. 31 articles were selected based on relevance to GPR-119’s therapeutic potential. The analysis included experimental trials using wild mice and rats, case reports, and controlled experiments using techniques including inflammatory biomarker analysis, metabolic profiling, and examination of liver tissues. Analysis of 92 peer-reviewed studies demonstrated that activation of gut-restricted GPR-119 agonists increased GLP-1 secretion and improved glucose tolerance in subjects presenting with metabolic disease. Overall, evidence suggests GPR-119 activation plays a significant role in incretin-mediated glucose regulation, inflammation control, and hepatic metabolic improvement. Monotherapy has shown effects on weight and glycemic outcomes. However, these outcomes have been enhanced when combined with DPP-4 inhibitors which amplify incretin signaling. Enhancement of multiple therapeutic treatments through receptor activation is yet to be explored.
GPR119 in Neurometabolic Control and Therapeutic Development
GPR-119 is a G protein-coupled receptor expressed in pancreatic beta cells and intestinal endocrine cells. Activation of GPR-119 through agonists has been studied for therapeutic developments, as it plays roles in glucose homeostasis, regulation of chronic inflammation, and appetite control. GPR-119 modulators can increase incretin secretion (GLP-1), without direct stimulation of insulin release—leading to enhanced glucose control, appetite reduction, and anti-inflammatory effects. Previous studies have highlighted gut-restricted agonists’ effectiveness in patients with metabolic diseases. This study aims to determine whether activation of restricted GPR-119 agonists affects body weight regulation, insulin secretion, and inflammation in patients with metabolic diseases compared to healthy patients. A literature review was conducted to evaluate the role of GPR-119 in metabolic pathways. A PubMed search utilizing “GPR-119” yielded 92 articles published across a 5-year period. 31 articles were selected based on relevance to GPR-119’s therapeutic potential. The analysis included experimental trials using wild mice and rats, case reports, and controlled experiments using techniques including inflammatory biomarker analysis, metabolic profiling, and examination of liver tissues. Analysis of 92 peer-reviewed studies demonstrated that activation of gut-restricted GPR-119 agonists increased GLP-1 secretion and improved glucose tolerance in subjects presenting with metabolic disease. Overall, evidence suggests GPR-119 activation plays a significant role in incretin-mediated glucose regulation, inflammation control, and hepatic metabolic improvement. Monotherapy has shown effects on weight and glycemic outcomes. However, these outcomes have been enhanced when combined with DPP-4 inhibitors which amplify incretin signaling. Enhancement of multiple therapeutic treatments through receptor activation is yet to be explored.
