Targeted inactivation of kinesin-1 in pancreatic ß-cells in vivo leads to insulin secretory deficiency.
Diabetes
; 60(1): 320-30, 2011 Jan.
Article
em En
| MEDLINE
| ID: mdl-20870970
ABSTRACT
OBJECTIVE:
Suppression of Kinesin-1 by antisense oligonucleotides, or overexpression of dominant-negative acting kinesin heavy chain, has been reported to affect the sustained phase of glucose-stimulated insulin secretion in ß-cells in vitro. In this study, we examined the in vivo physiological role of Kinesin-1 in ß-cell development and function. RESEARCH DESIGN ANDMETHODS:
A Cre-LoxP strategy was used to generate conditional knockout mice in which the Kif5b gene is specifically inactivated in pancreatic ß-cells. Physiological and histological analyses were carried out in Kif5b knockout mice as well as littermate controls.RESULTS:
Mice with ß-cell specific deletion of Kif5b (Kif5b(fl/)â»RIP2-Cre) displayed significantly retarded growth as well as slight hyperglycemia in both nonfasting and 16-h fasting conditions compared with control littermates. In addition, Kif5b(fl/)â»RIP2-Cre mice displayed significant glucose intolerance, which was not due to insulin resistance but was related to an insulin secretory defect in response to glucose challenge. These defects of ß-cell function in mutant mice were not coupled with observable changes in islet morphology, islet cell composition, or ß-cell size. However, compared with controls, pancreas of Kif5b(fl/)â»RIP2-Cre mice exhibited both reduced islet size and increased islet number, concomitant with an increased insulin vesicle density in ß-cells.CONCLUSIONS:
In addition to being essential for maintaining glucose homeostasis and regulating ß-cell function, Kif5b may be involved in ß-cell development by regulating ß-cell proliferation and insulin vesicle synthesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cinesinas
/
Células Secretoras de Insulina
/
Insulina
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article