Activation of SF1 neurons in the ventromedial hypothalamus by DREADD technology increases insulin sensitivity in peripheral tissues

Eulalia A. Coutinho, Shiki Okamoto, Ayako Wendy Ishikawa, Shigefumi Yokota, Nobuhiro Wada, Takahiro Hirabayashi, Kumiko Saito, Tatsuya Sato, Kazuyo Takagi, Chen Chi Wang, Kenta Kobayashi, Yoshihiro Ogawa, Seiji Shioda, Yumiko Yoshimura, Yasuhiko Minokoshi

研究成果: ジャーナルへの寄稿記事

12 引用 (Scopus)

抄録

The ventromedial hypothalamus (VMH) regulates glucose and energy metabolism in mammals. Optogenetic stimulation of VMH neurons that express steroidogenic factor 1 (SF1) induces hyperglycemia. However, leptin acting via the VMH stimulates whole-body glucose utilization and insulin sensitivity in some peripheral tissues, and this effect of leptin appears to be mediated by SF1 neurons. We examined the effects of activation of SF1 neurons with DREADD (designer receptors exclusively activated by designer drugs) technology. Activation of SF1 neurons by an intraperitoneal injection of clozapine-N-oxide (CNO), a specific hM3Dq ligand, reduced food intake and increased energy expenditure in mice expressing hM3Dq in SF1 neurons. It also increased whole-body glucose utilization and glucose uptake in red-type skeletal muscle, heart, and interscapular brown adipose tissue, as well as glucose production and glycogen phosphorylase a activity in the liver, thereby maintaining blood glucose levels. During hyperinsulinemic-euglycemic clamp, such activation of SF1 neurons increased insulin-induced glucose uptake in the same peripheral tissues and tended to enhance insulin-induced suppression of glucose production by suppressing gluconeogenic gene expression and glycogen phosphorylase a activity in the liver. DREADD technology is thus an important tool for studies of the role of the brain in the regulation of insulin sensitivity in peripheral tissues.

元の言語英語
ページ(範囲)2372-2386
ページ数15
ジャーナルDiabetes
66
発行部数9
DOI
出版物ステータス出版済み - 9 2017

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Designer Drugs
Steroidogenic Factor 1
Hypothalamus
Insulin Resistance
Technology
Neurons
Glucose
Phosphorylase a
Glycogen Phosphorylase
Leptin
Energy Metabolism
Optogenetics
Insulin
Glucose Clamp Technique
Brown Adipose Tissue
Liver
Intraperitoneal Injections
Hyperglycemia
Blood Glucose
Mammals

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

これを引用

Coutinho, E. A., Okamoto, S., Ishikawa, A. W., Yokota, S., Wada, N., Hirabayashi, T., ... Minokoshi, Y. (2017). Activation of SF1 neurons in the ventromedial hypothalamus by DREADD technology increases insulin sensitivity in peripheral tissues. Diabetes, 66(9), 2372-2386. https://doi.org/10.2337/db16-1344

Activation of SF1 neurons in the ventromedial hypothalamus by DREADD technology increases insulin sensitivity in peripheral tissues. / Coutinho, Eulalia A.; Okamoto, Shiki; Ishikawa, Ayako Wendy; Yokota, Shigefumi; Wada, Nobuhiro; Hirabayashi, Takahiro; Saito, Kumiko; Sato, Tatsuya; Takagi, Kazuyo; Wang, Chen Chi; Kobayashi, Kenta; Ogawa, Yoshihiro; Shioda, Seiji; Yoshimura, Yumiko; Minokoshi, Yasuhiko.

:: Diabetes, 巻 66, 番号 9, 09.2017, p. 2372-2386.

研究成果: ジャーナルへの寄稿記事

Coutinho, EA, Okamoto, S, Ishikawa, AW, Yokota, S, Wada, N, Hirabayashi, T, Saito, K, Sato, T, Takagi, K, Wang, CC, Kobayashi, K, Ogawa, Y, Shioda, S, Yoshimura, Y & Minokoshi, Y 2017, 'Activation of SF1 neurons in the ventromedial hypothalamus by DREADD technology increases insulin sensitivity in peripheral tissues', Diabetes, 巻. 66, 番号 9, pp. 2372-2386. https://doi.org/10.2337/db16-1344
Coutinho, Eulalia A. ; Okamoto, Shiki ; Ishikawa, Ayako Wendy ; Yokota, Shigefumi ; Wada, Nobuhiro ; Hirabayashi, Takahiro ; Saito, Kumiko ; Sato, Tatsuya ; Takagi, Kazuyo ; Wang, Chen Chi ; Kobayashi, Kenta ; Ogawa, Yoshihiro ; Shioda, Seiji ; Yoshimura, Yumiko ; Minokoshi, Yasuhiko. / Activation of SF1 neurons in the ventromedial hypothalamus by DREADD technology increases insulin sensitivity in peripheral tissues. :: Diabetes. 2017 ; 巻 66, 番号 9. pp. 2372-2386.
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abstract = "The ventromedial hypothalamus (VMH) regulates glucose and energy metabolism in mammals. Optogenetic stimulation of VMH neurons that express steroidogenic factor 1 (SF1) induces hyperglycemia. However, leptin acting via the VMH stimulates whole-body glucose utilization and insulin sensitivity in some peripheral tissues, and this effect of leptin appears to be mediated by SF1 neurons. We examined the effects of activation of SF1 neurons with DREADD (designer receptors exclusively activated by designer drugs) technology. Activation of SF1 neurons by an intraperitoneal injection of clozapine-N-oxide (CNO), a specific hM3Dq ligand, reduced food intake and increased energy expenditure in mice expressing hM3Dq in SF1 neurons. It also increased whole-body glucose utilization and glucose uptake in red-type skeletal muscle, heart, and interscapular brown adipose tissue, as well as glucose production and glycogen phosphorylase a activity in the liver, thereby maintaining blood glucose levels. During hyperinsulinemic-euglycemic clamp, such activation of SF1 neurons increased insulin-induced glucose uptake in the same peripheral tissues and tended to enhance insulin-induced suppression of glucose production by suppressing gluconeogenic gene expression and glycogen phosphorylase a activity in the liver. DREADD technology is thus an important tool for studies of the role of the brain in the regulation of insulin sensitivity in peripheral tissues.",
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