Polymorphism at the 5' end flanking region of the insulin gene is associated with reduced insulin secretion in healthy individuals.
Sixty-four unrelated healthy subjects were studied for the detection of a DNA polymorphism at the 5' end of the insulin gene. No significant difference between the groups was found in blood glucose values at fasting and after an oral glucose load. A significant association was found between fasting (P less than 0.05) and after load plasma C-peptide levels (P less than 0.01) and the presence of a 1.6 Kb insertion at the 5' end of the insulin gene. A gene dose-dependent effect was noted, class 3/3 individuals having the lowest after-load C-peptide concentration and class 1/3 an intermediate level (F for the linear trend: P = 0.007). This might suggest that insulin gene polymorphism affects insulin secretion in healthy individuals. In order to confirm this, a subgroup of six class 3/3 and eight class 1/1 individuals subsequently underwent a hyperglycaemic clamp. The tissue sensitivity to insulin was similar in the two groups but glucose-stimulated insulin secretion was markedly impaired in homozygotes for the class 3 allele. In this group, insulin secretion was, on average, only one-third of that in class 1/1 individuals (P less than 0.02). Similarly impaired in class 3/3 persons was the glucose + arginine-stimulated insulin secretion (P less than 0.05). We conclude that the polymorphism at the 5' end of the insulin gene is associated with variations in insulin secretion in healthy humans.
Cocozza
S
S
Dipartimento di Biologia e Patologia Cellulare e Molecolare, CNR, Napoli, Italy.
Riccardi
G
G
Monticelli
A
A
Capaldo
B
B
Genovese
S
S
Krogh
V
V
Celentano
E
E
Farinaro
E
E
Varrone
S
S
Avvedimento
V E
VE
D000328:Adult; D004247:DNA / Q000235:genetics*; D005260:Female; D005796:Genes; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D007328:Insulin; D004247:DNA