Dynamic Uni- and Multicellular Patterns Encode Biphasic Activity in Pancreatic Islets.
Diabetes
; 70(4): 878-888, 2021 04.
Article
en En
| MEDLINE
| ID: mdl-33468514
ABSTRACT
Biphasic secretion is an autonomous feature of many endocrine micro-organs to fulfill physiological demands. The biphasic activity of islet ß-cells maintains glucose homeostasis and is altered in type 2 diabetes. Nevertheless, underlying cellular or multicellular functional organizations are only partially understood. High-resolution noninvasive multielectrode array recordings permit simultaneous analysis of recruitment, of single-cell, and of coupling activity within entire islets in long-time experiments. Using this unbiased approach, we addressed the organizational modes of both first and second phase in mouse and human islets under physiological and pathophysiological conditions. Our data provide a new uni- and multicellular model of islet ß-cell activation during the first phase, small but highly active ß-cell clusters are dominant, whereas during the second phase, electrical coupling generates large functional clusters via multicellular slow potentials to favor an economic sustained activity. Postprandial levels of glucagon-like peptide 1 favor coupling only in the second phase, whereas aging and glucotoxicity alter coupled activity in both phases. In summary, biphasic activity is encoded upstream of vesicle pools at the micro-organ level by multicellular electrical signals and their dynamic synchronization between ß-cells. The profound alteration of the electrical organization of islets in pathophysiological conditions may contribute to functional deficits in type 2 diabetes.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Islotes Pancreáticos
/
Diabetes Mellitus Tipo 2
/
Células Secretoras de Insulina
/
Insulina
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Diabetes
Año:
2021
Tipo del documento:
Article
País de afiliación:
Francia