Version 1
: Received: 1 October 2024 / Approved: 1 October 2024 / Online: 1 October 2024 (14:27:52 CEST)
How to cite:
Janket, S.-J.; Chatanaka, M. K.; Sohaei, D.; Tamimi, F.; Meurman, J. H.; Diamandis, E. P. Incretin Agonism: Sustainable Efficacy or Surreptitious Hazard?. Preprints2024, 2024100047. https://doi.org/10.20944/preprints202410.0047.v1
Janket, S.-J.; Chatanaka, M. K.; Sohaei, D.; Tamimi, F.; Meurman, J. H.; Diamandis, E. P. Incretin Agonism: Sustainable Efficacy or Surreptitious Hazard?. Preprints 2024, 2024100047. https://doi.org/10.20944/preprints202410.0047.v1
Janket, S.-J.; Chatanaka, M. K.; Sohaei, D.; Tamimi, F.; Meurman, J. H.; Diamandis, E. P. Incretin Agonism: Sustainable Efficacy or Surreptitious Hazard?. Preprints2024, 2024100047. https://doi.org/10.20944/preprints202410.0047.v1
APA Style
Janket, S. J., Chatanaka, M. K., Sohaei, D., Tamimi, F., Meurman, J. H., & Diamandis, E. P. (2024). Incretin Agonism: Sustainable Efficacy or Surreptitious Hazard?. Preprints. https://doi.org/10.20944/preprints202410.0047.v1
Chicago/Turabian Style
Janket, S., Jukka H. Meurman and Eleftherios P. Diamandis. 2024 "Incretin Agonism: Sustainable Efficacy or Surreptitious Hazard?" Preprints. https://doi.org/10.20944/preprints202410.0047.v1
Abstract
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 by nutrient ingestion. The phenomenon that oral ingestion of glucose elicited much higher insulin secretion than intra-venous injection of equimolar glucose is known as incretin effect. This also alludes to the thesis that food intake is the root cause of insulin resistance.
Amylin is co-expressed with insulin from the pancreas β-cells but does not have insulinotropic function. Amylin suppresses glucagon secretion, slowing gastric emptying, and suppressing the central nervous system (CNS) reward center leading to weight loss. However, amylin can self-aggregate and cause serious cytotoxicity and may cause β-cell apoptosis.
Glucagon is secreted by the pancreatic α-cells and participates in glucose homeostasis in glucose-dependent manner. In hypoglycemia, glucagon increases blood glucose level by glycogenolysis and gluconeogenesis and inhibits glycogenesis in the liver. Some triple agonists in combination with glucagon and dual incretins are already being developed.
These advances bring to the question “Are the benefits of these anti-obesity treatments sustainable?” Chronic agonism may decrease the number of receptors. Also, long-term stimulation may cause β-cell exhaustion and failure. Additionally, instead of endogenous control of the appetite, exogenous control of satiety and food intake may hinder the long-term sustainability of these treatments. We will discuss the incretins’ mechanism of action, challenges, and future directions.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
