Targeted inactivation of Kinesin-1 in pancreatic β-cells in vivo leads to insulin secretory deficiency

Ju Cui, Zai Wang, Qianni Cheng, Raozhou Lin, Xin Mei Zhang, Po Sing Leung, Neal G. Copeland, Nancy A. Jenkins, Kwok Ming Yao, Jian Dong Huang

Research output: Contribution to journalArticle

36 Scopus citations

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 β-cells in vitro. In this study, we examined the in vivo physiological role of Kinesin-1 in β-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 β-cells. Physiological and histological analyses were carried out in Kif5b knockout mice as well as littermate controls. RESULTS: Mice with β-cell specific deletion of Kif5b (Kif5bfl/-: 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, Kif5bfl/-: 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 β-cell function in mutant mice were not coupled with observable changes in islet morphology, islet cell composition, or β-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 β-cells. CONCLUSIONS: In addition to being essential for maintaining glucose homeostasis and regulating β-cell function, Kif5b may be involved in β-cell development by regulating β-cell proliferation and insulin vesicle synthesis.

Original languageEnglish (US)
Pages (from-to)320-330
Number of pages11
JournalDiabetes
Volume60
Issue number1
DOIs
StatePublished - Jan 2011

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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