| pubmed-article:11078452 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11078452 | lifeskim:mentions | umls-concept:C0342276 | lld:lifeskim |
| pubmed-article:11078452 | lifeskim:mentions | umls-concept:C0241888 | lld:lifeskim |
| pubmed-article:11078452 | lifeskim:mentions | umls-concept:C0017337 | lld:lifeskim |
| pubmed-article:11078452 | lifeskim:mentions | umls-concept:C0221099 | lld:lifeskim |
| pubmed-article:11078452 | lifeskim:mentions | umls-concept:C0205217 | lld:lifeskim |
| pubmed-article:11078452 | lifeskim:mentions | umls-concept:C0920563 | lld:lifeskim |
| pubmed-article:11078452 | lifeskim:mentions | umls-concept:C0248419 | lld:lifeskim |
| pubmed-article:11078452 | lifeskim:mentions | umls-concept:C1256369 | lld:lifeskim |
| pubmed-article:11078452 | pubmed:issue | 11 | lld:pubmed |
| pubmed-article:11078452 | pubmed:dateCreated | 2000-11-15 | lld:pubmed |
| pubmed-article:11078452 | pubmed:abstractText | Diabetes resulting from heterozygosity for an inactivating mutation of the homeodomain transcription factor insulin promoter factor 1 (IPF-1) is due to a genetic defect of beta-cell function referred to as maturity-onset diabetes of the young 4. IPF-1 is required for the development of the pancreas and mediates glucose-responsive stimulation of insulin gene transcription. To quantitate islet cell responses in a family harboring a Pro63fsdelC mutation in IPF-1, we performed a five-step (1-h intervals) hyperglycemic clamp on seven heterozygous members (NM) and eight normal genotype members (NN). During the last 30 min of the fifth glucose step, glucagon-like peptide 1 (GLP-1) was also infused (1.5 pmol x kg(-1) x min(-1)). Fasting plasma glucose levels were greater in the NM group than in the NN group (9.2 vs. 5.9 mmol/l, respectively; P < 0.05). Fasting insulin levels were similar in both groups (72 vs. 105 pmol/l for NN vs. NM, respectively). First-phase insulin and C-peptide responses were absent in individuals in the NM group, who had markedly attenuated insulin responses to glucose alone compared with the NN group. At a glucose level of 16.8 mmol/l above fasting level, GLP-1 augmented insulin secretion equivalently (fold increase) in both groups, but the insulin and C-peptide responses to GLP-1 were sevenfold less in the NM subjects than in the NN subjects. In both groups, glucagon levels fell during each glycemic plateau, and a further reduction occurred during the GLP-1 infusion. Sigmoidal dose-response curves of glucose clearance versus insulin levels during the hyperglycemic clamp in the two small groups showed both a left shift and a lower maximal response in the NM group compared with the NN group, which is consistent with an increased insulin sensitivity in the NM subjects. A sharp decline occurred in the dose-response curve for suppression of nonesterified fatty acids versus insulin levels in the NM group. We conclude that the Pro63fsdelC IPF-1 mutation is associated with a severe impairment of beta-cell sensitivity to glucose and an apparent increase in peripheral tissue sensitivity to insulin and is a genetically determined cause of beta-cell dysfunction. | lld:pubmed |
| pubmed-article:11078452 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11078452 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11078452 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11078452 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11078452 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11078452 | pubmed:citationSubset | AIM | lld:pubmed |
| pubmed-article:11078452 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:11078452 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11078452 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:11078452 | pubmed:issn | 0012-1797 | lld:pubmed |
| pubmed-article:11078452 | pubmed:author | pubmed-author:HabenerJ FJF | lld:pubmed |
| pubmed-article:11078452 | pubmed:author | pubmed-author:ElahiDD | lld:pubmed |
| pubmed-article:11078452 | pubmed:author | pubmed-author:ClarkeW LWL | lld:pubmed |
| pubmed-article:11078452 | pubmed:author | pubmed-author:HanksJ BJB | lld:pubmed |
| pubmed-article:11078452 | pubmed:author | pubmed-author:EganJ MJM | lld:pubmed |
| pubmed-article:11078452 | pubmed:author | pubmed-author:WidemanLL | lld:pubmed |
| pubmed-article:11078452 | pubmed:author | pubmed-author:MullerD CDC | lld:pubmed |
| pubmed-article:11078452 | pubmed:author | pubmed-author:StoffersD ADA | lld:pubmed |
| pubmed-article:11078452 | pubmed:author | pubmed-author:ChiuG LGL | lld:pubmed |
| pubmed-article:11078452 | pubmed:author | pubmed-author:ClocquetA RAR | lld:pubmed |
| pubmed-article:11078452 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:11078452 | pubmed:volume | 49 | lld:pubmed |
| pubmed-article:11078452 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11078452 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11078452 | pubmed:pagination | 1856-64 | lld:pubmed |
| pubmed-article:11078452 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
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| pubmed-article:11078452 | pubmed:meshHeading | pubmed-meshheading:11078452... | lld:pubmed |
| pubmed-article:11078452 | pubmed:year | 2000 | lld:pubmed |
| pubmed-article:11078452 | pubmed:articleTitle | Impaired insulin secretion and increased insulin sensitivity in familial maturity-onset diabetes of the young 4 (insulin promoter factor 1 gene). | lld:pubmed |
| pubmed-article:11078452 | pubmed:affiliation | Geriatric Research Laboratory, Massachusetts General Hospital, Boston 02114, USA. | lld:pubmed |
| pubmed-article:11078452 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:11078452 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:11078452 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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