HNF1α controls renal glucose reabsorption in mouse and man

Recently it has been shown that dominant mutations in the human hepatocyte nuclear factor 1 alpha (HNF1 alpha) 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). HNF1 alpha -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 HNF1 alpha directly controls SGLT2 gene expression. Together these data indicate that HNF1 alpha plays a key role in glucose homeostasis in mammals.