Alterations in ß-Cell Calcium Dynamics and Efficacy Outweigh Islet Mass Adaptation in Compensation of Insulin Resistance and Prediabetes Onset.
Diabetes
; 65(9): 2676-85, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-27207518
ABSTRACT
Emerging insulin resistance is normally compensated by increased insulin production of pancreatic ß-cells, thereby maintaining normoglycemia. However, it is unclear whether this is achieved by adaptation of ß-cell function, mass, or both. Most importantly, it is still unknown which of these adaptive mechanisms fail when type 2 diabetes develops. We performed longitudinal in vivo imaging of ß-cell calcium dynamics and islet mass of transplanted islets of Langerhans throughout diet-induced progression from normal glucose homeostasis, through compensation of insulin resistance, to prediabetes. The results show that compensation of insulin resistance is predominated by alterations of ß-cell function, while islet mass only gradually expands. Hereby, functional adaptation is mediated by increased calcium efficacy, which involves Epac signaling. Prior to prediabetes, ß-cell function displays decreased stimulated calcium dynamics, whereas islet mass continues to increase through prediabetes onset. Thus, our data reveal a predominant role of islet function with distinct contributions of triggering and amplifying pathway in the in vivo processes preceding diabetes onset. These findings support protection and recovery of ß-cell function as primary goals for prevention and treatment of diabetes and provide insight into potential therapeutic targets.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estado Pré-Diabético
/
Cálcio
/
Ilhotas Pancreáticas
/
Células Secretoras de Insulina
/
Obesidade
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article