Source:http://linkedlifedata.com/resource/pubmed/id/16443774
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2006-1-30
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pubmed:abstractText |
Heterozygous mutations in the transcription factors hepatocyte nuclear factor (HNF)-1alpha and -1beta result in MODY (maturity-onset diabetes of the young). Despite structural similarity between HNF-1alpha and -1beta, HNF-1beta mutation carriers have hyperinsulinemia, whereas HNF-1alpha mutation carriers have normal or reduced insulin concentrations. We examined whether HNF-1beta mutation carriers are insulin resistant. The endogenous glucose production rate and rate of glucose uptake were measured with a two-step, low-dose (0.3 mU . kg(-1) . min(-1)) and high-dose (1.5 mU . kg(-1) . min(-1)) hyperinsulinemic-euglycemic clamp, with an infusion of [6,6-(2)H(2)]glucose, in six subjects with HNF-1alpha mutations, six subjects with HNF-1beta mutations, and six control subjects, matched for age, sex, and BMI. Endogenous glucose production rate was not suppressed by low-dose insulin in HNF-1beta subjects but was suppressed by 89% in HNF-1alpha subjects (P = 0.004) and 80% in control subjects (P < 0.001). Insulin-stimulated glucose uptake and suppression of lipolysis were similar in all groups at low- and high-dose insulin. Subjects with HNF-1beta mutations have reduced insulin sensitivity of endogenous glucose production but normal peripheral insulin sensitivity. This is likely to reflect reduced action of HNF-1beta in the liver and possibly the kidney. This may be mediated through regulation by HNF-1beta of the key gluconeogenic enzymes glucose-6-phosphatase or PEPCK.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Nonesterified,
http://linkedlifedata.com/resource/pubmed/chemical/Glucagon,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Nuclear Factor 1-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Nuclear Factor 1-beta,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0012-1797
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
55
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
405-11
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16443774-Adult,
pubmed-meshheading:16443774-Dose-Response Relationship, Drug,
pubmed-meshheading:16443774-Fatty Acids, Nonesterified,
pubmed-meshheading:16443774-Female,
pubmed-meshheading:16443774-Glucagon,
pubmed-meshheading:16443774-Glucose,
pubmed-meshheading:16443774-Glucose Clamp Technique,
pubmed-meshheading:16443774-Hepatocyte Nuclear Factor 1-alpha,
pubmed-meshheading:16443774-Hepatocyte Nuclear Factor 1-beta,
pubmed-meshheading:16443774-Humans,
pubmed-meshheading:16443774-Insulin,
pubmed-meshheading:16443774-Insulin Resistance,
pubmed-meshheading:16443774-Male,
pubmed-meshheading:16443774-Mutation
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pubmed:year |
2006
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pubmed:articleTitle |
Contrasting insulin sensitivity of endogenous glucose production rate in subjects with hepatocyte nuclear factor-1beta and -1alpha mutations.
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pubmed:affiliation |
Department of Diabetes and Endocrinology, Royal Surrey County Hospital, Guildford, UK.
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pubmed:publicationType |
Journal Article,
Controlled Clinical Trial,
Research Support, Non-U.S. Gov't
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