{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:42:01Z","timestamp":1791297721980,"version":"4.1.0"},"reference-count":25,"publisher":"American Diabetes Association","issue":"9","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,9,1]]},"abstract":"<jats:p>Hepatocyte nuclear factor-1\u03b1 (HNF-1\u03b1) mutations are the most common cause of maturity-onset diabetes of the young. HNF-1\u03b1 homozygous knockout mice exhibit a renal Fanconi syndrome with glucosuria and generalized aminoaciduria in addition to diabetes. We investigated glucosuria and aminoaciduria in patients with HNF-1\u03b1 mutations. Sixteen amino acids were measured in urine samples from patients with HNF-1\u03b1 mutations, age-matched nondiabetic control subjects, and age-matched type 1 diabetic patients, type 2 diabetic patients, and patients with diabetes and chronic renal failure. The HNF-1\u03b1 patients had glucosuria at lower glycemic control (as shown by HbA1c) than type 1 and type 2 diabetic patients, consistent with a lower renal glucose threshold. The HNF-1\u03b1 patients had a generalized aminoaciduria with elevated levels of 14 of 16 amino acids and an increased mean Z score for all amino acids compared with control subjects (0.66 vs. 0.00; P &amp;lt; 0.0005). Generalized aminoaciduria was also present in type 1 diabetic (Z score, 0.80; P &amp;lt; 0.0001), type 2 diabetic (Z score, 0.71; P &amp;lt; 0.0002), and chronic renal failure (Z score, 0.65; P &amp;lt; 0.01) patients. Aminoaciduria was not associated with microalbuminuria or proteinuria but was associated with glucosuria (1.00 glucosuria vs. 0.19 no glucosuria; P = 0.002). In type 1 diabetic patients, urine samples taken on the same day showed significantly more aminoaciduria when glucosuria was present compared with when it was absent (P &amp;lt; 0.01). In conclusion, HNF-1\u03b1 mutation carriers have a mutation-specific defect of proximal tubular glucose transport, resulting in increased glucosuria. In contrast, the generalized aminoaciduria seen in patients with HNF-1\u03b1 mutations is a general feature of patients with diabetes and glucosuria. Glucose may depolarize and dissipate the electrical gradient of the sodium-dependent amino acid transporters in the proximal renal tubule, causing a reduction in amino acid resorption.<\/jats:p>","DOI":"10.2337\/diabetes.50.9.2047","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"2047-2052","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":60,"title":["The Generalized Aminoaciduria Seen in Patients With Hepatocyte Nuclear Factor-1\u03b1 Mutations Is a Feature of All Patients With Diabetes and Is Associated With Glucosuria"],"prefix":"10.2337","volume":"50","author":[{"given":"Coralie","family":"Bingham","sequence":"first","affiliation":[{"name":"Department of Vascular Medicine and Diabetes Research, School of Postgraduate Medicine and Health Sciences, University of Exeter, Devon, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian","family":"Ellard","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine and Diabetes Research, School of Postgraduate Medicine and Health Sciences, University of Exeter, Devon, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Royal Devon and Exeter Healthcare NHS Trust, Barrack Road, Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Pennock","sequence":"additional","affiliation":[{"name":"Lewis Laboratory, Southmead Hospital, Westbury-On-Trym, Bristol, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Allen","sequence":"additional","affiliation":[{"name":"Lewis Laboratory, Southmead Hospital, Westbury-On-Trym, Bristol, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan J.","family":"James","sequence":"additional","affiliation":[{"name":"Royal Devon and Exeter Healthcare NHS Trust, Barrack Road, Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon C.","family":"Satchell","sequence":"additional","affiliation":[{"name":"Royal Devon and Exeter Healthcare NHS Trust, Barrack Road, Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice B.","family":"Salzmann","sequence":"additional","affiliation":[{"name":"Royal Devon and Exeter Healthcare NHS Trust, Barrack Road, Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T.","family":"Hattersley","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine and Diabetes Research, School of Postgraduate Medicine and Health Sciences, University of Exeter, Devon, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031207043589600_R1","doi-asserted-by":"crossref","unstructured":"Mendel DB, Hansen LP, Graves MK, Conley PB, Crabtree GR: HNF-1a and HNF-1b (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro. 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