Dopamine signalling in pancreatic islet cells and role in adaptations to metabolic stress.
J Pharm Pharmacol
; 76(7): 861-872, 2024 Jul 05.
Article
en En
| MEDLINE
| ID: mdl-38652540
ABSTRACT
OBJECTIVES:
Dopamine and related receptors are evidenced in pancreatic endocrine tissue, but the impact on islet ß-cell stimulus-secretion as well as (patho)physiological role are unclear.METHODS:
The present study has evaluated islet cell signalling pathways and biological effects of dopamine, as well as alterations of islet dopamine in rodent models of diabetes of different aetiology. KEYFINDINGS:
The dopamine precursor l-DOPA partially impaired glucose tolerance in mice and attenuated glucose-, exendin-4, and alanine-induced insulin secretion. The latter effect was echoed by the attenuation of glucose-induced [Ca2+]i dynamics and elevation of ATP levels in individual mouse islet cells. l-DOPA significantly decreased ß-cell proliferation rates, acting predominantly via the D2 receptor, which was most abundant at the mRNA level. The administration of streptozotocin (STZ) or high-fat diet (HFD) in mice significantly elevated numbers of dopamine-positive islet cells, with HFD also increasing colocalization of dopamine with insulin. At the same time, colocalization of dopamine with glucagon was increased in STZ-treated and pregnant mice, but unaffected by HFD.CONCLUSION:
These findings highlight a role for dopamine receptor signalling in islet cell biology adaptations to various forms of metabolic stress.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Dopamina
/
Dieta Alta en Grasa
/
Insulina
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
J Pharm Pharmacol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Reino Unido