Pontoglio M
Oncogenic Virus Unit, CNRS URA 1644, Biotechnology Department, Pasteur Institute, Paris, France.
J Am Soc Nephrol. 2000 Nov;11 Suppl 16:S140-3.
Hepatocyte nuclear factor 1 (HNF1) is a transcription factor involved in the regulation of a large set of hepatic genes, including albumin, beta-fibrinogen, and alpha1-antitrypsin. HNF1 is expressed in the liver, digestive tract, pancreas, and kidney. Mice lacking HNF1 exhibit hepatic, pancreatic, and renal dysfunctions. HNF1-deficient mice fail to express the hepatic phenylalanine hydroxylase gene, giving rise to hyperphenylalaninemia. Renal proximal tubular reabsorption of glucose, phosphate, arginine, and other metabolites is affected, producing severe renal glucosuria, phosphaturia, and amino aciduria. Homozygous mutant mice also exhibit a dramatic insulin secretion defect. This dysfunction resembles that exhibited by patients with maturity-onset diabetes mellitus of the young type 3, who carry mutations in the human HNF1 gene in the heterozygous state. These data show that HNF1 is a major regulator of glucose homeostasis, regulating the expression of genes that are expressed in the liver, kidney, and pancreas.
肝细胞核因子1（HNF1）是一种转录因子，参与调控大量肝脏基因的表达，包括白蛋白、β-纤维蛋白原和α1-抗胰蛋白酶。HNF1在肝脏、消化道、胰腺和肾脏中表达。缺乏HNF1的小鼠表现出肝脏、胰腺和肾脏功能障碍。HNF1缺陷型小鼠无法表达肝脏苯丙氨酸羟化酶基因，导致高苯丙氨酸血症。肾脏近端小管对葡萄糖、磷酸盐、精氨酸和其他代谢产物的重吸收受到影响，产生严重的肾性糖尿、磷尿和氨基酸尿。纯合突变小鼠还表现出明显的胰岛素分泌缺陷。这种功能障碍类似于年轻型3成年发病型糖尿病患者所表现出的功能障碍，这些患者在杂合状态下携带人类HNF1基因突变。这些数据表明，HNF1是葡萄糖稳态的主要调节因子，调控在肝脏、肾脏和胰腺中表达的基因。
