Related Experiment Video
Updated: Jul 1, 2026

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
Role of the ENPP1 K121Q polymorphism in glucose homeostasis
Roberto Baratta1, Paola Rossetti, Sabrina Prudente
1Unit of Endocrinology, Department of Internal and Specialistic Medicine, University of Catania Medical School, Garibaldi Hospital, Catania, Italy.
Objective:
To study the role of the ENPP1 Q121 variant on glucose homeostasis in whites from Italy.
Research Design And 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.
Related Concept Videos
Cell Specific Gene Expression
Glucose Homeostasis: Regulation of Blood Glucose
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
Other Glycolytic Pathways
Glucose Transporters
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
Insulin and C-peptide are co-secreted in...
cAMP-dependent Protein Kinase Pathways
