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Cardiac ischemia-reperfusion injury under insulin-resistant conditions: SGLT1 but not SGLT2 plays a compensatory protective role in diet-induced obesity.
Yoshii, Akira; Nagoshi, Tomohisa; Kashiwagi, Yusuke; Kimura, Haruka; Tanaka, Yoshiro; Oi, Yuhei; Ito, Keiichi; Yoshino, Takuya; Tanaka, Toshikazu D; Yoshimura, Michihiro.
Afiliación
  • Yoshii A; Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Nagoshi T; Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan. tnagoshi@jikei.ac.jp.
  • Kashiwagi Y; Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Kimura H; Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Tanaka Y; Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Oi Y; Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Ito K; Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Yoshino T; Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Tanaka TD; Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Yoshimura M; Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Cardiovasc Diabetol ; 18(1): 85, 2019 07 01.
Article en En | MEDLINE | ID: mdl-31262297
ABSTRACT

BACKGROUND:

Recent large-scale clinical trials have shown that SGLT2-inhibitors reduce cardiovascular events in diabetic patients. However, the regulation and functional role of cardiac sodium-glucose cotransporter (SGLT1 is the dominant isoform) compared with those of other glucose transporters (insulin-dependent GLUT4 is the major isoform) remain incompletely understood. Given that glucose is an important preferential substrate for myocardial energy metabolism under conditions of ischemia-reperfusion injury (IRI), we hypothesized that SGLT1 contributes to cardioprotection during the acute phase of IRI via enhanced glucose transport, particularly in insulin-resistant phenotypes. METHODS AND

RESULTS:

The hearts from mice fed a high-fat diet (HFD) for 12 weeks or a normal-fat diet (NFD) were perfused with either the non-selective SGLT-inhibitor phlorizin or selective SGLT2-inhibitors (tofogliflozin, ipragliflozin, canagliflozin) during IRI using Langendorff model. After ischemia-reperfusion, HFD impaired left ventricular developed pressure (LVDP) recovery compared with the findings in NFD. Although phlorizin-perfusion impaired LVDP recovery in NFD, a further impaired LVDP recovery and a dramatically increased infarct size were observed in HFD with phlorizin-perfusion. Meanwhile, none of the SGLT2-inhibitors significantly affected cardiac function or myocardial injury after ischemia-reperfusion under either diet condition. The plasma membrane expression of GLUT4 was significantly increased after IRI in NFD but was substantially attenuated in HFD, the latter of which was associated with a significant reduction in myocardial glucose uptake. In contrast, SGLT1 expression at the plasma membrane remained constant during IRI, regardless of the diet condition, whereas SGLT2 was not detected in the hearts of any mice. Of note, phlorizin considerably reduced myocardial glucose uptake after IRI, particularly in HFD.

CONCLUSIONS:

Cardiac SGLT1 but not SGLT2 plays a compensatory protective role during the acute phase of IRI via enhanced glucose uptake, particularly under insulin-resistant conditions, in which IRI-induced GLUT4 upregulation is compromised.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Florizina / Glucemia / Resistencia a la Insulina / Daño por Reperfusión Miocárdica / Miocitos Cardíacos / Transportador 1 de Sodio-Glucosa / Transportador 2 de Sodio-Glucosa / Inhibidores del Cotransportador de Sodio-Glucosa 2 / Obesidad Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cardiovasc Diabetol Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / ENDOCRINOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Florizina / Glucemia / Resistencia a la Insulina / Daño por Reperfusión Miocárdica / Miocitos Cardíacos / Transportador 1 de Sodio-Glucosa / Transportador 2 de Sodio-Glucosa / Inhibidores del Cotransportador de Sodio-Glucosa 2 / Obesidad Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cardiovasc Diabetol Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / ENDOCRINOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Japón
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