Genetic factors and insulin secretion: gene variants in the IGF genes.
IGFs are important regulators of pancreatic beta-cell development, growth, and maintenance. Mutations in the IGF genes have been found to be associated with type 2 diabetes, myocardial infarction, birth weight, and obesity. These associations could result from changes in insulin secretion. We have analyzed glucose-stimulated insulin secretion using hyperglycemic clamps in carriers of a CA repeat in the IGF-I promoter and an ApaI polymorphism in the IGF-II gene. Normal and impaired glucose-tolerant subjects (n = 237) were independently recruited from three different populations in the Netherlands and Germany to allow independent replication of associations. Both first- and second-phase insulin secretion were not significantly different between the various IGF-I or IGF-II genotypes. Remarkably, noncarriers of the IGF-I CA repeat allele had both a reduced insulin sensitivity index (ISI) and disposition index (DI), suggesting an altered balance between insulin secretion and insulin action. Other diabetes-related parameters were not significantly different for both the IGF-I and IGF-II gene variant. We conclude that gene variants in the IGF-I and IGF-II genes are not associated with detectable variations in glucose-stimulated insulin secretion in these three independent populations. Further studies are needed to examine the exact contributions of the IGF-I CA repeat alleles to variations in ISI and DI.
't Hart
Leen M
LM
Deparment of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
Fritsche
Andreas
A
Rietveld
Ingrid
I
Dekker
Jacqueline M
JM
Nijpels
Giel
G
Machicao
Fausto
F
Stumvoll
Michael
M
van Duijn
Cornelia M
CM
Häring
Hans U
HU
Heine
Robert J
RJ
Maassen
J Antonie
JA
van Haeften
Timon W
TW
D000328:Adult; D000483:Alleles; D001786:Blood Glucose / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D005858:Germany; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D015203:Reproducibility of Results
D001786:Blood Glucose; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II