Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations.

Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations. Research Abstract Details 

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Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations. Abstract Text:

OBJECTIVE: Mutations in the highly homologous transcription factors hepatocyte nuclear factor (HNF)-1alpha and -1beta cause maturity-onset diabetes of the young types 3 and 5, respectively. Diabetes due to HNF-1alpha mutations is well characterized. However, physiological assessment of the HNF-1beta phenotype is limited. We aimed to test the hypothesis that the diabetes phenotype due to HNF-1beta mutations is similar to that in HNF-1alpha. RESEARCH DESIGN AND METHODS: Fasting biochemistry and a tolbutamide-modified intravenous glucose tolerance test (IVGTT) were compared in matched HNF-1beta, HNF-1alpha, type 2 diabetic, and control subjects. Homeostasis model assessment indexes were determined from fasting insulin and glucose. The peak measures for the insulin increment after tolbutamide and for the insulin increment after glucose were determined from the IVGTT. RESULTS: The HNF-1beta patients showed a 2.4-fold reduction in insulin sensitivity compared with the HNF-1alpha patients (P = 0.001) with fasting insulin concentrations 2.7-fold higher (P = 0.004). HNF-1beta patients had lower HDL cholesterol (1.17 vs. 1.46 mmol/l; P = 0.009) and higher triglyceride (2.2 vs. 1.35 mmol/l; P = 0.015) levels than HNF-1alpha patients. The HNF-1beta patients had similar beta-cell responses to tolbutamide and glucose as the type 2 diabetic patients, but in the HNF-1alpha patients, the tolbutamide response was considerably increased relative to the response to glucose (P = 0.002). CONCLUSIONS: HNF-1beta patients have a different diabetes phenotype than HNF-1alpha patients. Those with HNF-1beta mutations have hyperinsulinemia and associated dyslipidemia consistent with insulin resistance and may have a different beta-cell defect. This suggests that despite considerable homology and a shared binding site, HNF-1alpha and HNF-1beta have a different role in maintaining normal glucose homeostasis. This result suggests a new etiological pathway for insulin resistance involving HNF-1beta.

Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations. Publishing Authors By Initials

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

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Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations. Journal Published:

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

Journal: Diabetes care

VOLUME: 27

Page Numbers: 1102-7

Journal Abbreviation: Diabetes Care

ISSN: 0149-5992

DAY: 14

MONTH: May

YEAR: 2004

Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations. Information

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LANGUAGE: eng

NlmUniqueID: 7805975

Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations. Keywords Mesh Terms:

KEYWORDS: Transcription Factors

MESH TERMS: genetics

Chemical & Substance for Abstract: Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations. Information

Substance Name: Hepatocyte Nuclear Factor 1-beta

Registry Number: 138674-15-4

Grant and Affiliation Information for Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations.

AFFILIATION: Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, UK.

Country: United States

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MEDLINETA: Diabetes Care

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