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Pathogenesis of diabesity‐induced kidney disease: role of kidney nutrient sensing
Author(s) -
Hinden Liad,
KogotLevin Aviram,
Tam Joseph,
Leibowitz Gil
Publication year - 2022
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15790
Subject(s) - nutrient sensing , kidney , kidney disease , medicine , diabetes mellitus , acute kidney injury , inflammation , fibrosis , signal transduction , pharmacology , endocrinology , biology , microbiology and biotechnology
Diabetes kidney disease (DKD) is a major healthcare problem associated with increased risk for developing end‐stage kidney disease and high mortality. It is widely accepted that DKD is primarily a glomerular disease. Recent findings however suggest that kidney proximal tubule cells (KPTCs) may play a central role in the pathophysiology of DKD. In diabetes and obesity, KPTCs are exposed to nutrient overload, including glucose, free‐fatty acids and amino acids, which dysregulate nutrient and energy sensing by mechanistic target of rapamycin complex 1 and AMP‐activated protein kinase, with subsequent induction of tubular injury, inflammation, and fibrosis. Pharmacological treatments that modulate nutrient sensing and signaling in KPTCs, including cannabinoid‐1 receptor antagonists and sodium glucose transporter 2 inhibitors, exert robust kidney protective effects. Shedding light on how nutrients are sensed and metabolized in KPTCs and in other kidney domains, and on their effects on signal transduction pathways that mediate kidney injury, is important for understanding the pathophysiology of DKD and for the development of novel therapeutic approaches in DKD and probably also in other forms of kidney disease.