The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance

L. Frittitta, R. Baratta, D. Spampinato, R. Di Paola, A. Pizzuti, R. Vigneri, V. Trischitta

Research output: Contribution to journalArticle

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Abstract

PC-1 is a membrane glycoprotein that impairs insulin receptor function. Its K121Q polymorphism is a genetic determinant of insulin resistance. We investigated whether the PC-1 gene modulates insulin sensitivity independently of weight status (i.e. both in nonobese and obese individuals). Nondiabetic subjects [164 males, 267 females; age, 37 ± 0.6 yr, mean ± SEM; body mass index (BMI), 32.7 ± 0.5 kg/m2], who were subdivided into 220 nonobese (BMI ≤ 29.9) and 211 obese, were studied. Although subjects were nondiabetic by selection criteria, plasma insulin concentrations during oral glucose tolerance test were higher (P <0.05) in Q allele-carrying subjects (K121Q or Q121Q genotypes), compared with K121K individuals, in both the nonobese and obese groups. Insulin sensitivity, measured by euglycemic clamp in a representative subgroup of 131 of 431 randomly selected subjects, progressively decreased (P <0.001) from nonobese K121K [n = 61; glucose disposal (M) = 34.9 ± 1.1 μ mol/kg/min] to nonobese Q (n = 21; M = 29.9 ± 2.0), obese K121K (n = 31, M = 18.5 ± 1.2), and obese Q (n = 18, M = 15.5 ± 1.2) carriers. The K121Q polymorphism was correlated with insulin sensitivity independently (P <0.05) of BMI, gender, age, and waist circumference. In conclusion, the Q121 PC-1 variant and obesity have independent and additive effects in causing insulin resistance.

Original languageEnglish
Pages (from-to)5888-5891
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number12
DOIs
Publication statusPublished - 2001

Fingerprint

Insulin Resistance
Obesity
Insulin
Body Mass Index
Polymorphism
Glucose Clamp Technique
Insulin Receptor
Membrane Glycoproteins
Waist Circumference
Glucose
Glucose Tolerance Test
Patient Selection
Clamping devices
Alleles
Genotype
Weights and Measures
Genes
Plasmas
Scanning electron microscopy

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance. / Frittitta, L.; Baratta, R.; Spampinato, D.; Di Paola, R.; Pizzuti, A.; Vigneri, R.; Trischitta, V.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 86, No. 12, 2001, p. 5888-5891.

Research output: Contribution to journalArticle

Frittitta, L. ; Baratta, R. ; Spampinato, D. ; Di Paola, R. ; Pizzuti, A. ; Vigneri, R. ; Trischitta, V. / The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance. In: Journal of Clinical Endocrinology and Metabolism. 2001 ; Vol. 86, No. 12. pp. 5888-5891.
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abstract = "PC-1 is a membrane glycoprotein that impairs insulin receptor function. Its K121Q polymorphism is a genetic determinant of insulin resistance. We investigated whether the PC-1 gene modulates insulin sensitivity independently of weight status (i.e. both in nonobese and obese individuals). Nondiabetic subjects [164 males, 267 females; age, 37 ± 0.6 yr, mean ± SEM; body mass index (BMI), 32.7 ± 0.5 kg/m2], who were subdivided into 220 nonobese (BMI ≤ 29.9) and 211 obese, were studied. Although subjects were nondiabetic by selection criteria, plasma insulin concentrations during oral glucose tolerance test were higher (P <0.05) in Q allele-carrying subjects (K121Q or Q121Q genotypes), compared with K121K individuals, in both the nonobese and obese groups. Insulin sensitivity, measured by euglycemic clamp in a representative subgroup of 131 of 431 randomly selected subjects, progressively decreased (P <0.001) from nonobese K121K [n = 61; glucose disposal (M) = 34.9 ± 1.1 μ mol/kg/min] to nonobese Q (n = 21; M = 29.9 ± 2.0), obese K121K (n = 31, M = 18.5 ± 1.2), and obese Q (n = 18, M = 15.5 ± 1.2) carriers. The K121Q polymorphism was correlated with insulin sensitivity independently (P <0.05) of BMI, gender, age, and waist circumference. In conclusion, the Q121 PC-1 variant and obesity have independent and additive effects in causing insulin resistance.",
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