Pharmacologic inhibition of somatostatin receptor 2 to restore glucagon counterregulation in diabetes.
| Autor: | Hoffman EG; School of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, ON, Canada., D'Souza NC; School of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, ON, Canada., Liggins RT; Zucara Therapeutics, Vancouver, BC, Canada., Riddell MC; School of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, ON, Canada. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in pharmacology [Front Pharmacol] 2024 Jan 17; Vol. 14, pp. 1295639. Date of Electronic Publication: 2024 Jan 17 (Print Publication: 2023). |
| DOI: | 10.3389/fphar.2023.1295639 |
| Abstrakt: | Glucose homeostasis is primarily maintained by pancreatic hormones, insulin and glucagon, with an emerging role for a third islet hormone, somatostatin, in regulating insulin and glucagon responses. Under healthy conditions, somatostatin secreted from pancreatic islet δ-cells inhibits both insulin and glucagon release through somatostatin receptor- induced cAMP-mediated downregulation and paracrine inhibition of β- and α-cells, respectively. Since glucagon is the body's most important anti-hypoglycemic hormone, and because glucagon counterregulation to hypoglycemia is lost in diabetes, the study of somatostatin biology has led to new investigational medications now in development that may help to restore glucagon counterregulation in type 1 diabetes. This review highlights the normal regulatory role of pancreatic somatostatin signaling in healthy islet function and how the inhibition of somatostatin receptor signaling in pancreatic α-cells may restore normal glucagon counterregulation in diabetes mellitus. Competing Interests: RL is an employee of Zucara Therapeutics Inc. MR serves on the Scientific Advisory Board and is a consultant for Zucara Therapeutics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Hoffman, D’Souza, Liggins and Riddell.) |
| Databáze: | MEDLINE |
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