| First Author | Cui J | Year | 2011 |
| Journal | Diabetes | Volume | 60 |
| Issue | 1 | Pages | 320-30 |
| PubMed ID | 20870970 | Mgi Jnum | J:170198 |
| Mgi Id | MGI:4944133 | Doi | 10.2337/db09-1078 |
| Citation | Cui J, et al. (2011) Targeted inactivation of kinesin-1 in pancreatic beta-cells in vivo leads to insulin secretory deficiency. Diabetes 60(1):320-30 |
| abstractText | 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 beta-cells in vitro. In this study, we examined the in vivo physiological role of Kinesin-1 in beta-cell development and function. RESEARCH DESIGN AND METHODS: A Cre-LoxP strategy was used to generate conditional knockout mice in which the Kif5b gene is specifically inactivated in pancreatic beta-cells. Physiological and histological analyses were carried out in Kif5b knockout mice as well as littermate controls. RESULTS: Mice with beta-cell specific deletion of Kif5b (Kif5b(fl/):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/):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 beta-cell function in mutant mice were not coupled with observable changes in islet morphology, islet cell composition, or beta-cell size. However, compared with controls, pancreas of Kif5b(fl/):RIP2-Cre mice exhibited both reduced islet size and increased islet number, concomitant with an increased insulin vesicle density in beta-cells. CONCLUSIONS: In addition to being essential for maintaining glucose homeostasis and regulating beta-cell function, Kif5b may be involved in beta-cell development by regulating beta-cell proliferation and insulin vesicle synthesis. |
