E4orf1-induced reduction in endogenous insulin level is independent of pancreas endocrine function.
Int J Obes (Lond)
; 46(5): 918-925, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-35017714
ABSTRACT
BACKGROUND:
Obesity is often associated with hyperinsulinemia due to insulin resistance. In mice models of hyperinsulinemia, adenovirus-derived E4orf1 protein promotes glucose disposal via insulin-independent pathway, and reduces insulin response to glucose load, described as its "Insulin Sparing Action". This is likely because less insulin is needed for disposing glucose in presence of E4orf1, however, there are other potential possibilities. This study determined if E4orf1 reduces insulin response to glucose load because it a) suppresses the ability of pancreatic ß-cells to secret insulin, or b) upregulates glucagon production by the pancreas.METHODS:
C57BL/6J wild type (control) and transgenic C57BL/6J (E4orf1) mice that express E4orf1 protein in adipose tissue upon doxycycline feeding, were used. Post-doxycycline feeding, insulin and glucagon secretion in response to glibenclamide or phenylephrine were compared between the two groups. The pancreases were examined for histological changes.RESULTS:
In response to glibenclamide, E4orf1 mice secreted more insulin and exhibited lower blood glucose compared to control (47.4 ± 4.4 vs 27.4 ± 3.7 mg/dl, p < 0.003), but showed no difference in glucagon secretion. Post-phenylephrine injection, no differences were observed between the two groups for glucagon or insulin, except E4orf1 mice had a lower blood glucose rise after 10-min of injection compared to the control (39.7 ± 4.7 vs. 58.3 ± 7.5 mg/dl, p < 0.05). E4orf1 mice had significantly larger pancreatic islets and higher number of islets per mm2 tissue area. Neither the size nor the number of islets met the criteria of hypertrophy or hyperplasia. CONCLUSIONS/INTERPRETATION:
E4orf1 retains and may enhance the ability of the pancreases to secret insulin in response to insulin secretagogue. Glucagon does not seem to play a role in the Insulin Sparing Action of E4orf1. Overall, the histology studies support better pancreatic islet health in presence of E4orf1, compared to that in control mice. The "insulin-independent" role of E4orf1 has potential therapeutic implications in addressing hyperinsulinemia in obesity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ilhotas Pancreáticas
/
Proteínas E4 de Adenovirus
/
Células Secretoras de Insulina
/
Hiperinsulinismo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Int J Obes (Lond)
Assunto da revista:
METABOLISMO
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos