Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino acid hormone, secreted from the enteroendocrine K cells, which has insulin-releasing and extra-pancreatic actions. GIP and its receptor present a widespread distribution in the mammalian brain where they have been implicated with synaptic plasticity, neurogenesis, neuroprotection and behavioral alterations. This review attempts to provide a comprehensive picture of the role of GIP in the central nervous system and to highlight recent findings from our group showing its potential involvement in neurological illnesses including epilepsies, Parkinson's disease and Alzheimer's disease.
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http://dx.doi.org/10.1097/FBP.0b013e32833c8544 | DOI Listing |
Addiction
January 2025
Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, FL, USA.
J Med Chem
January 2025
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
GPR119 has emerged as a promising target for treating type 2 diabetes and associated obesity, as its stimulation induces the secretion of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide in the intestinal tract as well as the glucose-dependent release of insulin in pancreatic β-cells. We describe the design and synthesis of novel GPR119 agonists containing a 1,4-disubstituted cyclohexene scaffold. Compound displayed nanomolar potency (EC = 3.
View Article and Find Full Text PDFJ Cardiovasc Dev Dis
January 2025
Cedars Sinai Medical Center, Los Angeles, CA 90048, USA.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists (GIP/GLP-1 RAs) are emerging as effective treatments for obesity and cardiometabolic disease. This study evaluated physician perceptions of the safety and efficacy of semaglutide and tirzepatide through a questionnaire administered to 165 attending physicians specializing in internal or family medicine, with 122 responses received. Physicians reported an average patient weight loss of 9.
View Article and Find Full Text PDFDiabetes Obes Metab
January 2025
Research Center of Clinical Pharmacology, The First Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, China.
Objective: Previous experiments have demonstrated that BGM0504, a GLP-1R/GIPR dual agonist drug by molecular dynamics-guided optimization, had enhanced agonistic activity compared to tirzepatide. This study aims to investigate its safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in Chinese healthy volunteers.
Methods: A randomized, double-blind, placebo-controlled and dose-escalation Phase I study was conducted as follows: a single dose (2.
J Biol Chem
January 2025
Division of Experimental Animal, Hidaka Branch, Biomedical Research Center, Saitama Medical University, Saitama, Japan; Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan. Electronic address:
Recent success with the use of glucagon-like peptide-1 (GLP-1) receptor analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of patients with diabetes has highlighted the role of the intestine as an endocrine organ. Gut-derived hormones, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and ghrelin, have important roles in the control of energy metabolism and food intake, and are associated with the metabolic syndrome. In this study, we isolated and identified a new intestine-derived hormone, betagenin, and showed that it stimulates insulin secretion and β-cell proliferation and suppresses β-cell apoptosis.
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