Decreased insulin production and increased insulin sensitivity in the klotho mutant mouse, a novel animal model for human aging

T. Utsugi, T. Ohno, Y. Ohyama, T. Uchiyama, Y. Saito, Y. Matsumura, H. Aizawa, H. Itoh, M. Kurabayashi, S. Kawazu, S. Tomono, Y. Oka, T. Suga, M. Kuro-o, Y. Nabeshima, R. Nagai

研究成果: Article査読

123 被引用数 (Scopus)

抄録

We have recently identified a novel gene, klotho (kl), which may suppress several aging phenotypes. A defect of kl gene expression in the mouse results in a syndrome resembling human aging, such as arteriosclerosis, skin atrophy, osteoporosis, and pulmonary emphysema. To determine whether mouse homozygotes for the kl mutation (kl/kl) show abnormal glucose metabolism, an oral glucose tolerance test (OGTT) was performed at 6 to 8 weeks of age. Blood glucose levels during the OGTT were significantly lower in kl/kl mice versus wild-type mice. The insulin content of the pancreas was significantly lower in kl/kl mice compared with wild-type mice. Decreased insulin production was also supported by Northern blot analysis showing lower levels of insulin mRNA in kl/kl mice. To examine how lower blood glucose levels may exist in kl/kl mice despite decreased insulin production, insulin tolerance tests (ITTs) were performed. The glucose decline following insulin injection was more severe in kl/kl mice versus wild-type mice, suggesting that insulin sensitivity was higher in kl/kl mice versus wild-type mice. In kl/kl mice, an augmented expression of GLUT4 in skeletal muscle was demonstrated by both Northern blot analysis and Western blot analysis. Thus, we conclude that insulin production is decreased and insulin sensitivity is increased in the klotho mouse, a novel animal model for human aging. Copyright (C) 2000 by W.B. Saunders Company.

本文言語English
ページ(範囲)1118-1123
ページ数6
ジャーナルMetabolism: clinical and experimental
49
9
DOI
出版ステータスPublished - 2000
外部発表はい

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 内分泌学

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