Insulin-Independent Induction of Sterol Regulatory Element-Binding Protein-1c Expression in the Livers of Streptozotocin-Treated Mice

• Takashi Matsuzaka

  Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan

• Hitoshi Shimano

  Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan

• Naoya Yahagi

  Department of Metabolic Diseases, University of Tokyo, Tokyo, Japan

• Michiyo Amemiya-Kudo

  Department of Metabolic Diseases, University of Tokyo, Tokyo, Japan

• Hiroaki Okazaki

  Department of Metabolic Diseases, University of Tokyo, Tokyo, Japan

• Yoshiaki Tamura

  Department of Metabolic Diseases, University of Tokyo, Tokyo, Japan

• Yoko Iizuka

  Department of Metabolic Diseases, University of Tokyo, Tokyo, Japan

• Ken Ohashi

  Department of Metabolic Diseases, University of Tokyo, Tokyo, Japan

• Sachiko Tomita

  Department of Metabolic Diseases, University of Tokyo, Tokyo, Japan

• Motohiro Sekiya

  Department of Metabolic Diseases, University of Tokyo, Tokyo, Japan

• Alyssa Hasty

  Department of Metabolic Diseases, University of Tokyo, Tokyo, Japan

• Yoshimi Nakagawa

  Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan

• Hirohito Sone

  Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan

• Hideo Toyoshima

  Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan

• Shun Ishibashi

  Department of Metabolic Diseases, University of Tokyo, Tokyo, Japan

• Jun-ichi Osuga

  Department of Metabolic Diseases, University of Tokyo, Tokyo, Japan

• Nobuhiro Yamada

  Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan

抄録

Insulin and glucose together have been previously shown to regulate hepatic sterol regulatory element-binding protein (SREBP)-1c expression. We sought to explore the nutritional regulation of lipogenesis through SREBP-1c induction in a setting where effects of sugars versus insulin could be distinguished. To do so, mice were insulin depleted by streptozotocin (STZ) administration and subjected to a fasting-refeeding protocol with glucose, fructose, or sucrose. Unexpectedly, the insulin-depleted mice exhibited a marked induction of SREBP-1c on all sugars, and this increase in SREBP-1c was even more dramatic than in the non-STZ-administered controls. The time course of changes in SREBP-1 induction varied depending on the type of sugars in both control and STZ-administered mice. Glucose refeeding gave a peak of SREBP-1c induction, whereas fructose refeeding caused slow and gradual increments, and sucrose refeeding fell between these two responses. Expression of various lipogenic enzymes were also gradually increased over time, irrespective of the types of sugars, with greater intensities in STZ-administered than in nontreated mice. In contrast, induction of hepatic glucokinase and suppression of phoshoenolpyruvate carboxykinase were insulin dependent in an early refed state. These data clearly demonstrate that nutritional regulation of SREBP-1c and lipogenic genes may be completely independent of insulin as long as sufficient carbohydrates are available.

収録刊行物

• Diabetes

  Diabetes 53 (3), 560-569, 2004-03-01

  American Diabetes Association

キーワード

• Endocrinology, Diabetes and Metabolism
• Internal Medicine

詳細情報

• CRID: 1362544419109788800
• NII論文ID: 30026271710
• DOI: 10.2337/diabetes.53.3.560
• ISSN: 1939327X
• ISSN: 00121797
• Web Site: https://journals.org/diabetes/diabetes/article-pdf/53/3/560/656977/zdb00304000560.pdf
• Web Site: https://diabetesjournals.org/diabetes/article-pdf/53/3/560/656977/zdb00304000560.pdf
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