Role of the ENPP1 K121Q polymorphism in glucose homeostasis.
OBJECTIVE
To study the role of the ENPP1 Q121 variant on glucose homeostasis in whites from Italy.


METHODS
We conducted case-control studies in 764 adults (from two independent samples of 289 nonobese and 485 obese individuals) and 240 overweight/obese children undergoing oral glucose tolerance testing (OGTT). Early-phase insulin secretion and insulin sensitivity (the insulinogenic index and the insulin sensitivity index) and their interplay (the disposition index) were calculated.


RESULTS
In adult subjects, glucose profiles during OGTT were significantly (P = 2 x 10(-2)) different across K121Q genotype groups and higher in QQ than KK individuals (P = 5 x 10(-2)). The insulinogenic index was significantly reduced in QQ (18.5 +/- 3.4) compared with both KK (31.6 +/- 1.0; P = 2.2 x 10(-7)) and KQ (30.5 +/- 1.5; P = 3.2 x 10(-6)) individuals. KQ individuals also showed a reduced insulin sensitivity index compared with KK subjects (P = 3.6 x 10(-2)). The disposition index was lower in QQ carriers than in KQ and KK individuals (P = 8 x 10(-3) and 4 x 10(-4), respectively) and lower in KQ than in KK individuals (P = 3 x 10(-2)). Data obtained in overweight/obese children were very similar to those observed in adults, with QQ individuals showing (compared with KQ and KK subjects) a reduced insulinogenic index (P = 7 x 10(-3) and 2 x 10(-2), respectively) and disposition index (P = 2 x 10(-2) and 7 x 10(-3), respectively).


CONCLUSIONS
Homozygous carriers of the ENPP1 Q121 variant are characterized by an altered glucose homeostasis. Reduced early-phase insulin secretion and inefficient interplay between insulin secretion and sensitivity, which occur at early ages, are major determinants of this defect.
Baratta
Roberto
R
Unit of Endocrinology, Department of Internal and Specialistic Medicine, University of Catania Medical School, Garibaldi Hospital, Catania, Italy.
Rossetti
Paola
P
Prudente
Sabrina
S
Barbetti
Fabrizio
F
Sudano
Dora
D
Nigro
Angela
A
Farina
Maria Grazia
MG
Pellegrini
Fabio
F
Trischitta
Vincenzo
V
Frittitta
Lucia
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002648:Child; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D014644:Genetic Variation; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007558:Italy; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011755:Pyrophosphatases / Q000235:genetics*; D012016:Reference Values; D044465:White People / Q000235:genetics; D055815:Young Adult
D007328:Insulin; D004247:DNA; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; D005947:Glucose
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