Adrenoceptor Expression and Function in the Endocrine Pancreas.
Handb Exp Pharmacol
; 285: 639-664, 2024.
Article
en En
| MEDLINE
| ID: mdl-38872059
ABSTRACT
The sympathetic nervous system plays an important role in the regulation of endocrine pancreatic function, most importantly insulin release. Among the nine adrenoceptor (AR) subtypes, the α2A-AR appears to be the subtype most abundantly expressed in the human pancreas. While α2- and ß-AR have opposing effects, the net response to sympathetic stimulation is inhibition of insulin secretion mediated by α2-AR located in the plasma membrane of pancreatic ß cells. This inhibition may be present physiologically as evidenced by increased insulin secretion in healthy and diabetic humans and animals in response to α2-AR antagonists, a finding that was confirmed in all studies. Based on such data and on an association of an α2A-AR polymorphism, that increases receptor expression levels, with an elevated risk for diabetes, increased α2A-AR signaling in the pancreatic ß cells has been proposed as a risk factor for the development of type 2 diabetes. Thus, the α2A-AR was proposed as a drug target for the treatment of some forms of type 2 diabetes. Drug research and development programs leveraging this mechanism have reached the clinical stage, but none have resulted in an approved medicine due to a limited efficacy. While ß-AR agonists can increase circulating insulin levels in vivo, it remains controversial whether this includes a direct effect on ß cells or occurs secondary to general metabolic effects. Therefore, the regulation of endocrine pancreatic function is physiologically interesting but may be of limited therapeutic relevance.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores Adrenérgicos alfa 2
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Handb Exp Pharmacol
Año:
2024
Tipo del documento:
Article