In:
Diabetes, American Diabetes Association, Vol. 46, No. 4 ( 1997-04-01), p. 726-730
Kurzfassung:
One form of maturity-onset diabetes of the young (MODY3) results from mutations in the hepatocyte nuclear factor (HNF)-1α gene, located on chromosome 12q24.2. The primary objective of the present study was to search for genetic variation in the HNF-1α gene in nine nonrelated Danish Caucasian subjects with MODY. Direct sequencing of the coding region and intron-exon boundaries of the HNF-1α gene revealed 2 novel and 1 previously reported missense mutations and 2 novel frameshift mutations in five of nine MODY subjects. These five mutations were found in neither 84 NIDDM patients nor 84 control subjects. One glucose-tolerant lean male with a P447L missense mutation, which in his relatives caused MODY, underwent an oral glucose tolerance test (OGTT), a tolbutamide modified frequently sampled intravenous glucose tolerance test, and a glucagon test to examine for a possible early β-cell abnormality. He had a low insulin secretion rate during an OGTT, but a twofold increase in pancreatic β-cell response after intravenous glucose and a 2.5- to 4-fold increase in β-cell response after either intravenous tolbutamide or intravenous glucagon loads. In conclusion, 1) mutations in the HNF-1α gene are common in Danish Caucasian MODY patients, and 2) early stages in the pathogenesis of MODY3 caused by the P447L mutation may be characterized by a hyperexcitability of β-cells to intravenous secretagogues.
Materialart:
Online-Ressource
ISSN:
0012-1797
,
1939-327X
DOI:
10.2337/diab.46.4.726
Sprache:
Englisch
Verlag:
American Diabetes Association
Publikationsdatum:
1997
ZDB Id:
1501252-9
