The generalized aminoaciduria seen in patients with hepatocyte nuclear factor-1alpha mutations is a feature of all patients with diabetes and is associated with glucosuria.

The generalized aminoaciduria seen in patients with hepatocyte nuclear factor-1alpha mutations is a feature of all patients with diabetes and is associated with glucosuria. Research Abstract Details 

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The generalized aminoaciduria seen in patients with hepatocyte nuclear factor-1alpha mutations is a feature of all patients with diabetes and is associated with glucosuria. Abstract Text:

Hepatocyte nuclear factor-1alpha (HNF-1alpha) mutations are the most common cause of maturity-onset diabetes of the young. HNF-1alpha 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-1alpha mutations. Sixteen amino acids were measured in urine samples from patients with HNF-1alpha 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-1alpha 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-1alpha 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 < 0.0005). Generalized aminoaciduria was also present in type 1 diabetic (Z score, 0.80; P < 0.0001), type 2 diabetic (Z score, 0.71; P < 0.0002), and chronic renal failure (Z score, 0.65; P < 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 < 0.01). In conclusion, HNF-1alpha 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-1alpha 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.

The generalized aminoaciduria seen in patients with hepatocyte nuclear factor-1alpha mutations is a feature of all patients with diabetes and is associated with glucosuria. Publishing Authors By Initials

For similar proteins: transcription factors research abstracts see: proteins: transcription factors research

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The generalized aminoaciduria seen in patients with hepatocyte nuclear factor-1alpha mutations is a feature of all patients with diabetes and is associated with glucosuria. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Diabetes

VOLUME: 50

Page Numbers: 2047-52

Journal Abbreviation: Diabetes

ISSN: 0012-1797

DAY: 14

MONTH: Sep

YEAR: 2001

The generalized aminoaciduria seen in patients with hepatocyte nuclear factor-1alpha mutations is a feature of all patients with diabetes and is associated with glucosuria. Information

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LANGUAGE: eng

NlmUniqueID: 372763

The generalized aminoaciduria seen in patients with hepatocyte nuclear factor-1alpha mutations is a feature of all patients with diabetes and is associated with glucosuria. Keywords Mesh Terms:

KEYWORDS: Transcription Factors

MESH TERMS: genetics

Chemical & Substance for Abstract: The generalized aminoaciduria seen in patients with hepatocyte nuclear factor-1alpha mutations is a feature of all patients with diabetes and is associated with glucosuria. Information

Substance Name: Hepatocyte Nuclear Factor 1-beta

Registry Number: 138674-15-4

Grant and Affiliation Information for The generalized aminoaciduria seen in patients with hepatocyte nuclear factor-1alpha mutations is a feature of all patients with diabetes and is associated with glucosuria.

AFFILIATION: Department of Vascular Medicine and Diabetes Research, School of Postgraduate Medicine and Health Sciences, University of Exeter, Devon, UK.

Country: United States

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MEDLINETA: Diabetes

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