Glucose metabolism and insulin sensitivity in transgenic mice overexpressing leptin with lethal yellow agouti mutation: usefulness of leptin for the treatment of obesity-associated diabetes.

• H Masuzaki

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.

• Y Ogawa

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.

• M Aizawa-Abe

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.

• K Hosoda

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.

• J Suga

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.

• K Ebihara

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.

• N Satoh

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.

• H Iwai

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.

• G Inoue

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.

• H Nishimura

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.

• Y Yoshimasa

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.

• K Nakao

  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.

抄録

Leptin acts as an adipocyte-derived blood-borne satiety factor that can increase glucose metabolism. To elucidate the therapeutic implications of leptin for obesity-associated diabetes, we crossed transgenic skinny mice overexpressing leptin (Tg/+), which we have developed recently, and lethal yellow KKAy mice (Ay/+), a genetic model for obesity-diabetes syndrome, and examined the metabolic phenotypes of F1 animals. At 6 weeks of age, plasma leptin concentrations in Tg/+ mice with the Ay allele (Tg/+:Ay/+) were significantly higher than those in Ay/+ mice. Although no significant differences in body weight were noted among Tg/+:Ay/+ mice, Ay/+ mice, and their wild-type lean littermates (+/+), glucose and insulin tolerance tests revealed increased glucose tolerance and insulin sensitivity in Tg/+:Ay/+ compared with Ay/+ mice. However, at 12 weeks of age, when plasma leptin concentrations in Ay/+ mice were comparable to those in Tg/+:Ay/+ mice, Tg/+:Ay/+ mice developed obesity-diabetes syndrome similar to that of Ay/+ mice. Body weights of 12-week-old Tg/+:Ay/+ and Ay/+ mice were reduced to those of +/+ mice by a 3-week food restriction; when plasma leptin concentrations remained high in Tg/+:Ay/+ mice but were markedly reduced in Ay/+ and +/+ mice, glucose tolerance and insulin sensitivity in Tg/+:Ay/+ mice were markedly improved as compared with Ay/+ and +/+ mice. The present study demonstrates that hyperleptinemia can delay the onset of impaired glucose metabolism and accelerate the recovery from diabetes during caloric restriction in Tg/+:Ay/+ mice, thereby suggesting the potential usefulness of leptin in combination with a long-term caloric restriction for the treatment of obesity-associated diabetes.

収録刊行物

• Diabetes

  Diabetes 48 (8), 1615-1622, 1999-08-01

  American Diabetes Association

キーワード

• Endocrinology, Diabetes and Metabolism
• Internal Medicine

詳細情報

• CRID: 1362544418813897600
• NII論文ID: 30026274696
• NII書誌ID: AA00628057
• DOI: 10.2337/diabetes.48.8.1615
• ISSN: 1939327X
• ISSN: 00121797
• ISSN: http://id.crossref.org/issn/00121797
• Web Site: https://journals.org/diabetes/diabetes/article-pdf/48/8/1615/338193/10426381.pdf
• Web Site: https://diabetesjournals.org/diabetes/article-pdf/48/8/1615/338193/10426381.pdf
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