Autocrine IGF2 programmes ß-cell plasticity under conditions of increased metabolic demand.
Sci Rep
; 11(1): 7717, 2021 04 08.
Article
en En
| MEDLINE
| ID: mdl-33833312
ABSTRACT
When exposed to nutrient excess and insulin resistance, pancreatic ß-cells undergo adaptive changes in order to maintain glucose homeostasis. The role that growth control genes, highly expressed in early pancreas development, might exert in programming ß-cell plasticity in later life is a poorly studied area. The imprinted Igf2 (insulin-like growth factor 2) gene is highly transcribed during early life and has been identified in recent genome-wide association studies as a type 2 diabetes susceptibility gene in humans. Hence, here we investigate the long-term phenotypic metabolic consequences of conditional Igf2 deletion in pancreatic ß-cells (Igf2ßKO) in mice. We show that autocrine actions of IGF2 are not critical for ß-cell development, or for the early post-natal wave of ß-cell remodelling. Additionally, adult Igf2ßKO mice maintain glucose homeostasis when fed a chow diet. However, pregnant Igf2ßKO females become hyperglycemic and hyperinsulinemic, and their conceptuses exhibit hyperinsulinemia and placentomegalia. Insulin resistance induced by congenital leptin deficiency also renders Igf2ßKO females more hyperglycaemic compared to leptin-deficient controls. Upon high-fat diet feeding, Igf2ßKO females are less susceptible to develop insulin resistance. Based on these findings, we conclude that in female mice, autocrine actions of ß-cell IGF2 during early development determine their adaptive capacity in adult life.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factor II del Crecimiento Similar a la Insulina
/
Células Secretoras de Insulina
/
Plasticidad de la Célula
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Sci Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Reino Unido