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, Hiroshi Itoh, M. Kurabayashi, S. Kawazu, S. Tomono, Y. Oka, T. Suga, M. Kuro-o, Y. Nabeshima, R. Nagai

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1118-1123
Number of pages6
JournalMetabolism: Clinical and Experimental
Volume49
Issue number9
DOIs
Publication statusPublished - 2000
Externally publishedYes

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Insulin Resistance
Animal Models
Insulin
Glucose Tolerance Test
Northern Blotting
Blood Glucose
Glucose
Pulmonary Emphysema
Arteriosclerosis
Homozygote
Osteoporosis
Atrophy
Pancreas
Skeletal Muscle
Western Blotting
Phenotype
Gene Expression
Messenger RNA
Skin
Mutation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Decreased insulin production and increased insulin sensitivity in the klotho mutant mouse, a novel animal model for human aging. / Utsugi, T.; Ohno, T.; Ohyama, Y.; Uchiyama, T.; Saito, Y.; Matsumura, Y.; Aizawa, H.; Itoh, Hiroshi; Kurabayashi, M.; Kawazu, S.; Tomono, S.; Oka, Y.; Suga, T.; Kuro-o, M.; Nabeshima, Y.; Nagai, R.

In: Metabolism: Clinical and Experimental, Vol. 49, No. 9, 2000, p. 1118-1123.

Research output: Contribution to journalArticle

Utsugi, T, Ohno, T, Ohyama, Y, Uchiyama, T, Saito, Y, Matsumura, Y, Aizawa, H, Itoh, H, Kurabayashi, M, Kawazu, S, Tomono, S, Oka, Y, Suga, T, Kuro-o, M, Nabeshima, Y & Nagai, R 2000, 'Decreased insulin production and increased insulin sensitivity in the klotho mutant mouse, a novel animal model for human aging', Metabolism: Clinical and Experimental, vol. 49, no. 9, pp. 1118-1123. https://doi.org/10.1053/meta.2000.8606
Utsugi, T. ; Ohno, T. ; Ohyama, Y. ; Uchiyama, T. ; Saito, Y. ; Matsumura, Y. ; Aizawa, H. ; Itoh, Hiroshi ; Kurabayashi, M. ; Kawazu, S. ; Tomono, S. ; Oka, Y. ; Suga, T. ; Kuro-o, M. ; Nabeshima, Y. ; Nagai, R. / Decreased insulin production and increased insulin sensitivity in the klotho mutant mouse, a novel animal model for human aging. In: Metabolism: Clinical and Experimental. 2000 ; Vol. 49, No. 9. pp. 1118-1123.
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AU - Saito, Y.

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