Renal Tubular Handling of Glucose and Fructose in Health and Disease.

IF 4.2 2区 医学 Q1 PHYSIOLOGY Comprehensive Physiology Pub Date : 2021-12-29 DOI:10.1002/cphy.c210030
Volker Vallon, Takahiko Nakagawa
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Abstract

The proximal tubule of the kidney is programmed to reabsorb all filtered glucose and fructose. Glucose is taken up by apical sodium-glucose cotransporters SGLT2 and SGLT1 whereas SGLT5 and potentially SGLT4 and GLUT5 have been implicated in apical fructose uptake. The glucose taken up by the proximal tubule is typically not metabolized but leaves via the basolateral facilitative glucose transporter GLUT2 and is returned to the systemic circulation or used as an energy source by distal tubular segments after basolateral uptake via GLUT1. The proximal tubule generates new glucose in metabolic acidosis and the postabsorptive phase, and fructose serves as an important substrate. In fact, under physiological conditions and intake, fructose taken up by proximal tubules is primarily utilized for gluconeogenesis. In the diabetic kidney, glucose is retained and gluconeogenesis enhanced, the latter in part driven by fructose. This is maladaptive as it sustains hyperglycemia. Moreover, renal glucose retention is coupled to sodium retention through SGLT2 and SGLT1, which induces secondary deleterious effects. SGLT2 inhibitors are new anti-hyperglycemic drugs that can protect the kidneys and heart from failing independent of kidney function and diabetes. Dietary excess of fructose also induces tubular injury. This can be magnified by kidney formation of fructose under pathological conditions. Fructose metabolism is linked to urate formation, which partially accounts for fructose-induced tubular injury, inflammation, and hemodynamic alterations. Fructose metabolism favors glycolysis over mitochondrial respiration as urate suppresses aconitase in the tricarboxylic acid cycle, and has been linked to potentially detrimental aerobic glycolysis (Warburg effect). © 2022 American Physiological Society. Compr Physiol 12:2995-3044, 2022.

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健康和疾病中肾小管对葡萄糖和果糖的处理。
肾脏近端肾小管会重吸收所有滤过的葡萄糖和果糖。葡萄糖由肾顶端的钠-葡萄糖共转运体 SGLT2 和 SGLT1 吸收,而 SGLT5 以及潜在的 SGLT4 和 GLUT5 则与肾顶端的果糖吸收有关。近端肾小管摄取的葡萄糖通常不会被代谢,而是通过基底侧的促进性葡萄糖转运体 GLUT2 离开肾小管,经基底侧的 GLUT1 吸收后返回全身循环或被远端肾小管用作能量来源。在代谢性酸中毒和吸收后阶段,近端肾小管会产生新的葡萄糖,而果糖是一种重要的底物。事实上,在生理条件和摄入量下,近端肾小管吸收的果糖主要用于葡萄糖生成。在糖尿病肾脏中,葡萄糖被保留下来,而糖元生成得到加强,后者部分是由果糖驱动的。这种情况是不适应的,因为它会维持高血糖。此外,肾脏葡萄糖潴留通过 SGLT2 和 SGLT1 与钠潴留耦合,从而诱发继发性有害影响。SGLT2 抑制剂是新型抗高血糖药物,可保护肾脏和心脏免受衰竭,与肾功能和糖尿病无关。膳食中过量的果糖也会诱发肾小管损伤。在病理条件下,肾脏形成的果糖会加剧这种损伤。果糖代谢与尿酸盐的形成有关,这也是果糖诱发肾小管损伤、炎症和血液动力学改变的部分原因。果糖代谢有利于糖酵解而非线粒体呼吸,因为尿酸盐会抑制三羧酸循环中的丙酮酸酶,并与潜在的有害有氧糖酵解(沃伯格效应)有关。© 2022 美国生理学会。Compr Physiol 12:2995-3044, 2022.
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来源期刊
CiteScore
10.50
自引率
0.00%
发文量
38
审稿时长
6-12 weeks
期刊介绍: Comprehensive Physiology is the most authoritative and comprehensive collection of physiology information ever assembled, and uses the most powerful features of review journals and electronic reference works to cover the latest key developments in the field, through the most authoritative articles on the subjects covered. This makes Comprehensive Physiology a valued reference work on the evolving science of physiology for both researchers and clinicians. It also provides a useful teaching tool for instructors and an informative resource for medical students and other students in the life and health sciences.
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