Basigin deficiency prevents anaplerosis and ameliorates insulin resistance and hepatosteatosis.
Basigin deficiency prevents anaplerosis and ameliorates insulin resistance and hepatosteatosis.
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Basigin缺乏可防止同体，并改善胰岛素抵抗和肝抑制病。
DOI：
10.1172/jci.insight.142464
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发表时间：
2021-10-22
期刊：
影响因子：
8
通讯作者：
Kadomatsu K
中科院分区：
文献类型：
--
作者：
Ryuge A;Kosugi T;Maeda K;Banno R;Gou Y;Zaitsu K;Ito T;Sato Y;Hirayama A;Tsubota S;Honda T;Nakajima K;Ozaki T;Kondoh K;Takahashi K;Kato N;Ishimoto T;Soga T;Nakagawa T;Koike T;Arima H;Yuzawa Y;Minokoshi Y;Maruyama S;Kadomatsu K
单羧酸盐，如乳酸盐和丙酮酸盐，是生物合成途径的前体，包括通过三羧酸（TCA）循环和相邻代谢网络的葡萄糖、脂质和氨基酸的前体。单羧酸盐跨细胞膜的转运主要由单羧酸盐转运蛋白（MCT）进行，跨膜蛋白basigin（BSG）促进其膜定位和稳定。在这里，我们证明了MCT/BSG轴位于细胞代谢的关键交叉点。通过Bsg耗竭实现了质膜中MCT 1的消除，这通过阻止乳酸和丙酮酸流入细胞而导致细胞再生障碍，从而抑制TCA循环。这种净回补抑制部分地被增加的生糖氨基酸利用所补偿（例如，丙氨酸和谷氨酰胺）进入TCA循环和通过脂肪酸β-氧化活化生酮。补充这些观察，高血糖症和肝脂肪变性诱导的高脂肪饮食得到改善，在Bsg缺陷小鼠。此外，Bsg缺乏显着改善高脂饮食诱导的胰岛素抵抗。总之，通过BSG抑制对乳酸和丙酮酸转运的质膜选择性调节可以增强代谢灵活性以治疗代谢性疾病。
Monocarboxylates, such as lactate and pyruvate, are precursors for biosynthetic pathways, including those for glucose, lipids, and amino acids via the tricarboxylic acid (TCA) cycle and adjacent metabolic networks. The transportation of monocarboxylates across the cellular membrane is performed primarily by monocarboxylate transporters (MCTs), the membrane localization and stabilization of which are facilitated by the transmembrane protein basigin (BSG). Here, we demonstrate that the MCT/BSG axis sits at a crucial intersection of cellular metabolism. Abolishment of MCT1 in the plasma membrane was achieved by Bsg depletion, which led to gluconeogenesis impairment via preventing the influx of lactate and pyruvate into the cell, consequently suppressing the TCA cycle. This net anaplerosis suppression was compensated in part by the increased utilization of glycogenic amino acids (e.g., alanine and glutamine) into the TCA cycle and by activated ketogenesis through fatty acid β-oxidation. Complementary to these observations, hyperglycemia and hepatic steatosis induced by a high-fat diet were ameliorated in Bsg-deficient mice. Furthermore, Bsg deficiency significantly improved insulin resistance induced by a high-fat diet. Taken together, the plasma membrane–selective modulation of lactate and pyruvate transport through BSG inhibition could potentiate metabolic flexibility to treat metabolic diseases.
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缺乏酮己激酶-A加剧链蛋白酶诱导的糖尿病小鼠的肾脏损伤。
DOI：
10.1016/j.metabol.2018.03.020
发表时间：
2018-08
期刊：
Metabolism: clinical and experimental
影响因子：
--
作者：
Doke T;Ishimoto T;Hayasaki T;Ikeda S;Hasebe M;Hirayama A;Soga T;Kato N;Kosugi T;Tsuboi N;Lanaspa MA;Johnson RJ;Kadomatsu K;Maruyama S
通讯作者：
Maruyama S
影响因子：
4.6
作者：
Ito T;Ishigami M;Matsushita Y;Hirata M;Matsubara K;Ishikawa T;Hibi H;Ueda M;Hirooka Y;Goto H;Yamamoto A
通讯作者：
Yamamoto A
影响因子：
13.5
作者：
Ishimoto, Takuji;Lanaspa, Miguel A.;Rivard, Christopher J.;Roncal-Jimenez, Carlos A.;Orlicky, David J.;Cicerchi, Christina;McMahan, Rachel H.;Abdelmalek, Manal F.;Rosen, Hugo R.;Jackman, Matthew R.;MacLean, Paul S.;Diggle, Christine P.;Asipu, Aruna;Inaba, Shinichiro;Kosugi, Tomoki;Sato, Waichi;Maruyama, Shoichi;Sanchez-Lozada, Laura G.;Sautin, Yuri Y.;Hill, James O.;Bonthron, David T.;Johnson, Richard J.
通讯作者：
Johnson, Richard J.
影响因子：
4.8
作者：
Burgess, Shawn C.;Leone, Teresa C.;Finck, Brian N.
通讯作者：
Finck, Brian N.
影响因子：
29.4
作者：
Kirk E;Reeds DN;Finck BN;Mayurranjan SM;Patterson BW;Klein S
通讯作者：
Klein S