Incretin Agonism: Sustainable Efficacy or Surreptitious Hazard?

• DOI: 10.20944/preprints202410.0047.v1
• Publication Date: 2024-10-02T11:53:59Z
• Authors: Sok-Ja Janket; Miyo K. Chatanaka; Dorsa Sohaei; Faleh Tamimi; Jukka H. Meurman; Eleftherios P. Di...
• Keywords: Agonism; Incretin

Recent clinical trials using synthetic incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have demonstrated that these treatments ameliorated many complications related to obesity, emphasizing the significant impact of body weight on overall health. Incretins are enteroendocrine hormones secreted by gut endothelial cells triggered nutrient ingestion. The phenomenon oral ingestion glucose elicited much higher insulin secretion than intra-venous injection equimolar is known as effect. This also alludes thesis food intake root cause resistance. Amylin co-expressed with from pancreas β-cells but does not function. suppresses glucagon secretion, slowing gastric emptying, suppressing central nervous system (CNS) reward center leading loss. However, amylin can self-aggregate serious cytotoxicity may β-cell apoptosis. Glucagon pancreatic α-cells participates in homeostasis manner. In hypoglycemia, increases blood level glycogenolysis gluconeogenesis inhibits glycogenesis liver. Some triple combination dual incretins already being developed. These advances bring question “Are benefits anti-obesity sustainable?” Chronic agonism decrease number receptors. Also, long-term stimulation exhaustion failure. Additionally, instead endogenous control appetite, exogenous satiety hinder sustainability treatments. We will discuss incretins’ mechanism action, challenges, future directions.