A transgenic dwarf rat model as a tool for the study of calorie restriction and aging

Haruyoshi Yamaza; Toshimitsu Komatsu; Takuya Chiba; Hiroaki Toyama; Kazuo To; Yoshikazu Higami; Isao Shimokawa

doi:10.1016/j.exger.2003.11.001

A transgenic dwarf rat model as a tool for the study of calorie restriction and aging

Haruyoshi Yamaza, Toshimitsu Komatsu, Takuya Chiba, Hiroaki Toyama, Kazuo To, Yoshikazu Higami, Isao Shimokawa^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

Abstract

We have previously reported a long-lived transgenic dwarf rat model, in which the growth hormone (GH)-insulin like growth factor (IGF)-1 axis was selectively suppressed by overexpression of antisense GH transgene. Rats heterozygous for the transgene (tg/-) manifest phenotypes similar to those in calorie-restricted (CR) rats. To further characterize the transgenic rat in comparison with CR rats, the present study evaluated glucose and insulin tolerance in tg/- and control Wistar (-/-) rats at 6-9 months of age. Rats were fed ad libitum (AL) or 30% CR from 6 weeks of age. In CR rats, glucose disposal after glucose load was facilitated without any significant surge of serum insulin, and insulin tolerance test also indicated increased insulin sensitivity. In transgenic rats, similar findings were observed after glucose and insulin load, and CR in tg/- rats further facilitated glucose disposal during glucose and insulin tolerance tests. These findings suggest the presence of both common and separate mechanisms regulating the glucose-insulin system between CR and the reduced GH-IGF-1 axis paradigms. The transgenic rat model is, therefore, a useful one for studies of CR and aging.

Original language	English
Pages (from-to)	269-272
Number of pages	4
Journal	Experimental Gerontology
Volume	39
Issue number	2
DOIs	https://doi.org/10.1016/j.exger.2003.11.001
Publication status	Published - 2004 Feb
Externally published	Yes

Keywords

Calorie restriction
Glucose
Growth hormone
IGF-1
Insulin
Transgenic rat

ASJC Scopus subject areas

Biochemistry
Ageing
Molecular Biology
Genetics
Endocrinology
Cell Biology

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10.1016/j.exger.2003.11.001

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title = "A transgenic dwarf rat model as a tool for the study of calorie restriction and aging",

abstract = "We have previously reported a long-lived transgenic dwarf rat model, in which the growth hormone (GH)-insulin like growth factor (IGF)-1 axis was selectively suppressed by overexpression of antisense GH transgene. Rats heterozygous for the transgene (tg/-) manifest phenotypes similar to those in calorie-restricted (CR) rats. To further characterize the transgenic rat in comparison with CR rats, the present study evaluated glucose and insulin tolerance in tg/- and control Wistar (-/-) rats at 6-9 months of age. Rats were fed ad libitum (AL) or 30% CR from 6 weeks of age. In CR rats, glucose disposal after glucose load was facilitated without any significant surge of serum insulin, and insulin tolerance test also indicated increased insulin sensitivity. In transgenic rats, similar findings were observed after glucose and insulin load, and CR in tg/- rats further facilitated glucose disposal during glucose and insulin tolerance tests. These findings suggest the presence of both common and separate mechanisms regulating the glucose-insulin system between CR and the reduced GH-IGF-1 axis paradigms. The transgenic rat model is, therefore, a useful one for studies of CR and aging.",

keywords = "Calorie restriction, Glucose, Growth hormone, IGF-1, Insulin, Transgenic rat",

author = "Haruyoshi Yamaza and Toshimitsu Komatsu and Takuya Chiba and Hiroaki Toyama and Kazuo To and Yoshikazu Higami and Isao Shimokawa",

note = "Funding Information: We thank Yutaka Araki and the staff in the laboratory animal center at Nagasaki University School of Medicine for their excellent technical support. We also thank Nippon Institute for Biological Science for providing the transgenic rat. This work was supported by the Research Grant for longevity Sciences (grants 11-C) from the Ministry of Health, Welfare, and Labor of Japan.",

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doi = "10.1016/j.exger.2003.11.001",

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T1 - A transgenic dwarf rat model as a tool for the study of calorie restriction and aging

AU - Yamaza, Haruyoshi

AU - Komatsu, Toshimitsu

AU - Chiba, Takuya

AU - Toyama, Hiroaki

AU - To, Kazuo

AU - Higami, Yoshikazu

AU - Shimokawa, Isao

N1 - Funding Information: We thank Yutaka Araki and the staff in the laboratory animal center at Nagasaki University School of Medicine for their excellent technical support. We also thank Nippon Institute for Biological Science for providing the transgenic rat. This work was supported by the Research Grant for longevity Sciences (grants 11-C) from the Ministry of Health, Welfare, and Labor of Japan.

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N2 - We have previously reported a long-lived transgenic dwarf rat model, in which the growth hormone (GH)-insulin like growth factor (IGF)-1 axis was selectively suppressed by overexpression of antisense GH transgene. Rats heterozygous for the transgene (tg/-) manifest phenotypes similar to those in calorie-restricted (CR) rats. To further characterize the transgenic rat in comparison with CR rats, the present study evaluated glucose and insulin tolerance in tg/- and control Wistar (-/-) rats at 6-9 months of age. Rats were fed ad libitum (AL) or 30% CR from 6 weeks of age. In CR rats, glucose disposal after glucose load was facilitated without any significant surge of serum insulin, and insulin tolerance test also indicated increased insulin sensitivity. In transgenic rats, similar findings were observed after glucose and insulin load, and CR in tg/- rats further facilitated glucose disposal during glucose and insulin tolerance tests. These findings suggest the presence of both common and separate mechanisms regulating the glucose-insulin system between CR and the reduced GH-IGF-1 axis paradigms. The transgenic rat model is, therefore, a useful one for studies of CR and aging.

AB - We have previously reported a long-lived transgenic dwarf rat model, in which the growth hormone (GH)-insulin like growth factor (IGF)-1 axis was selectively suppressed by overexpression of antisense GH transgene. Rats heterozygous for the transgene (tg/-) manifest phenotypes similar to those in calorie-restricted (CR) rats. To further characterize the transgenic rat in comparison with CR rats, the present study evaluated glucose and insulin tolerance in tg/- and control Wistar (-/-) rats at 6-9 months of age. Rats were fed ad libitum (AL) or 30% CR from 6 weeks of age. In CR rats, glucose disposal after glucose load was facilitated without any significant surge of serum insulin, and insulin tolerance test also indicated increased insulin sensitivity. In transgenic rats, similar findings were observed after glucose and insulin load, and CR in tg/- rats further facilitated glucose disposal during glucose and insulin tolerance tests. These findings suggest the presence of both common and separate mechanisms regulating the glucose-insulin system between CR and the reduced GH-IGF-1 axis paradigms. The transgenic rat model is, therefore, a useful one for studies of CR and aging.

KW - Calorie restriction

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KW - IGF-1

KW - Insulin

KW - Transgenic rat

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A transgenic dwarf rat model as a tool for the study of calorie restriction and aging

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