Targeted Inactivation of Kinesin-1 in Pancreatic β-Cells In Vivo Leads to Insulin Secretory Deficiency

  1. Jian-Dong Huang1
  1. 1Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong;
  2. 2Department of Physiology, The Chinese University of Hong Kong, Hong Kong;
  3. 3Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
  1. Corresponding author: Jian-Dong Huang, jdhuang{at}, or Kwok-Ming Yao, kmyao{at}


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 Kif5bfl/: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.


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  • Received July 26, 2009.
  • Accepted September 20, 2010.

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  1. Diabetes vol. 60 no. 1 320-330
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