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HNF1α controls renal glucose reabsorption in mouse and man
Author(s) -
Pontoglio Marco,
Prié Dominique,
Cheret Claire,
Doyen Antonia,
Leroy Christine,
Froguel Philippe,
Velho Gilberto,
Yaniv Moshe,
Friedlander Gérard
Publication year - 2000
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kvd071
Subject(s) - hepatocyte nuclear factors , endocrinology , medicine , renal glucose reabsorption , reabsorption , biology , kidney , glucose homeostasis , maturity onset diabetes of the young , diabetes mellitus , urinary system , gene expression , type 2 diabetes , gene , genetics , insulin resistance
Recently it has been shown that dominant mutations in the human hepatocyte nuclear factor 1 α (HNF1α) gene, encoding for a homeoprotein that is expressed in liver, kidney, pancreas and intestine, result in maturity onset diabetes of the young type 3 (MODY3). HNF1α‐null mice are diabetic, but at the same time suffer from a renal Fanconi syndrome characterized by urinary glucose loss. Here we show that MODY3 patients are also characterized by a reduced tubular reabsorption of glucose. The renal murine defect is due to reduced expression of the low affinity/high capacity glucose cotransporter (SGLT2). Our results show that HNF1α directly controls SGLT2 gene expression. Together these data indicate that HNF1α plays a key role in glucose homeostasis in mammals.