The purpose of this study was to investigate whether the efficacy of exercise training as a means of insulin resistance syndrome (IRS) treatment is dependent on the PC-1 gene K121Q variants. A population of 84 abdominally obese Korean women was analyzed prospectively. Before and after a 12-week exercise (walking) training program, indices of body fatness including body mass index, percent body fat, and waist circumference, and cardiorespiratory fitness were measured. Total cholesterol (TC), triacylglycerol, high-density lipoprotein cholesterol (HDLC), glucose, and insulin were measured in fasting venous blood. At baseline, KK individuals had significantly lower waist circumference (p = 0.019) and TC (p = 0.001) than KQ/QQ individuals did. In particular, compared with KQ/QQ individuals, KK individuals had significantly greater reductions in body weight (p = 0.002), BMI (p = 0.032), and fasting insulin (p = 0.042), and a greater increase in HDLC (p = <0.001), following the 12-week walking exercise program. This study suggests that the PC-1 gene K121Q polymorphism may modulate responses of IRS to exercise training, at least in this population.
Key words
Korean women - obesity phenotype - gene polymorphism
References
1
Almind K, Doria A, Khan C R.
Putting the genes for type II diabetes on the map.
Nat Med.
2001;
7
277-279
2 American College of Sports Medicine .ACSM's Resource Manual for Guideline for Exercise Testing and Prescription. Philadelphia, PA; Lippincott Williams & Wilkins 2006: 76-79
3
Beck-Nielsen H, Groop L C.
Metabolic and genetic characterization of prediabetic states. Sequence of events leading to non-insulin-dependent diabetes mellitus.
J Clin Invest.
1994;
94
1714-1721
4
Bense L.
Impact of moderate aerobic exercise training on insulin sensitivity in type 2 diabetic men treated with oral hypoglycemic agents: is insulin sensitivity enhanced only in non-obese subjects?.
Med Sci Monit.
2002;
8
LE23
5
Buckley M F, Loveland K A, McKinstry W J, Garson O M, Goding J W.
Plasma cell membrane glycoprotein PC‐1. cDNA cloning of the human molecule, amino acid sequence, and chromosomal location.
J Biol Chem.
1990;
265
17506-17511
6
Ceesay S M, Prentice A M, Day K C, Murgatroyd P R, Goldberg G R, Scott W, Spurr G B.
The use of heart rate monitoring in the estimation of energy expenditure: a validation study using indirect whole-body calorimetry.
Br J Nutr.
1989;
61
175-186
7
Constanzo B V, Trischitta V, Di Paola R, Spampinato D, Pizzuti A, Vigneri R, Frittitta L.
The Q allele variant (GLN121) of membrane glycoprotein PC‐1 interacts with insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (LYS121).
Diabetes.
2001;
50
831-836
8
Dengel D R, Pratley R E, Hagberg J M, Rogus E M, Goldberg A P.
Distinct effects of aerobic exercise training and weight loss on glucose homeostasis in obese sedentary men.
J Appl Physiol.
1996;
81
318-325
9
Friedewald W T, Levy R I, Fredrickson D S.
Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
Clin Chem.
1972;
18
499-502
10
Frittitta L, Spampinato D, Solini A, Nosadini R, Goldfine I D, Vigneri R, Trischitta V.
Elevated PC‐1 content in cultured skin fibroblasts correlates with the decreased in vivo and in vitro insulin action in non diabetic subjects.
Diabetes.
1998;
47
1095-1110
11
Frittitta L, Youngren J, Vigneri R, Maddux B A, Trischitta V, Goldfine I D.
PC‐1 content in skeletal muscle of non-obese, non-diabetic subjects: relationship to insulin receptor tyrosine-kinase and whole body insulin sensitivity.
Diabetologia.
1996;
39
1190-1195
12
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.
J Clin Endocrinol Metab.
2001;
86
5888-5891
13
Funakoshi I, Kato H, Horie K, Yano T, Hori Y, Kobayashi H, Inoue T, Suzuki H, Fukui S, Tsukahara M, Kajii T, Yamashima I.
Molecular cloning of cDNAs for human fibroblast nucleotide pyrophosphate.
Arch Biochem Biophys.
1992;
295
180-187
14
Gonzalez-Sanchez J L, Martinez-Larrad M T, Fernandez-Perez C, Kubaszek A, Laakso M, Serrano-Rios M.
K121Q PC‐1 gene polymorphism is not associated with insulin resistance in a Spanish population.
Obes Res.
2003;
11
603-605
15
Grarup N, Urhammer S A, Ek J, Albrechtsen A, Glumer C, Borch-Johnsen K, Jorgensen T, Hansen T, Pedersen O.
Studies of the relationship between the ENPP1 K121Q polymorphism and type 2 diabetes, insulin resistance and obesity in 7330 Danish white subjects.
Diabetologia.
2006;
49
2097-2104
16
Gu H F, Almgren P, Lindholm E, Frittitta L, Pizzuti A, Trischitta V, Groop L C.
Association between the human glycoprotein PC‐1 gene and elevated glucose and insulin levels in a paired-sibling analysis.
Diabetes.
2000;
49
1601-1603
17
Halverstadt A, Phares D A, Ferrell R E, Wilund K R, Goldberg A P, Hagberg J M.
High-density lipoprotein-cholesterol, its subfractions, and responses to exercise training are dependent on endothelial lipase genotype.
Metabolism.
2003;
52
1505-1511
19
Kubaszek A, Pihlajamaki J, Karhapaa P, Vauhkonen I, Laakso M.
The K121Q polymorphism of the PC‐1 gene is associated with insulin resistance but not with dyslipidemia.
Diabetes Care.
2003;
26
464-467
20
Lakka T A, Rankinen T, Weisnagel S J, Changnon Y C, Lakka H M, Ukkola O, Boule N, Rice T, Leon A S, Skinner J S, Wilmore J H, Rao D C, Bergman R, Bouchard C.
Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis in response to exercise in nondiabetic individuals: the HERITAGE family study.
Diabetes.
2004;
53
1603-1608
21
Maddux B A, Sbraccia P, Kumakura S, Sasson S, Youngren J, Fisher A, Spencer S, Grupe A, Henzel W, Stewart T A, Reaven G, Goldfine I D.
Membrane glycoprotein PC‐1 and insulin resistance in non-insulin-dependent diabetes mellitus.
Nature.
1995;
373
448-451
22
Matsuoka N, Patki A, Tiwari H K, Allison D B, Johnson S B, Gregersen P K, Leibel R L, Chung W K.
Association of K121Q polymorphism in ENPP1 (PC‐1) with BMI in Caucasian and African-American adults.
Int J Obes (Lond).
2006;
30
233-237
23
Matthews D R, Hosker J P, Rudenski A S, Naylor B A, Treacher D F, Turner R C.
Homeostasis model assessment: insulin resistance and beta cell function from fasting plasma glucose and insulin concentrations in man.
Diabetologia.
1985;
28
412-419
24
Meyre D, Bouatia-Naji N, Tounian A, Samson C, Lecoeur C, Vatin V, Ghoussaini M, Wachter C, Hercberg S, Charpentier G, Patsch W, Pattou F, Charles M A, Tounian P, Clement K, Jouret B, Weill J, Maddux B A, Goldfine I D, Walley A, Boutin P, Dina C, Froguel P.
Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes.
Nat Genet.
2005;
37
863-867
25
Pizzuti A, Frittitta L, Argiolas A, Baratta R, Goldfine I D, Bozzali M, Ercolino T, Scarlato G, Iacoviello L, Vigneri R, Tassi V, Trischitta V.
A polymorphism (K121Q) of the human glycoprotein PC‐1 gene coding region is strongly associated with insulin resistance.
Diabetes.
1999;
48
1881-1884
26
Ramussen Sk, Urhammer S A, Pizzuti A, Echwald S M, Ekstrom C T, Hansen L, Hansen T, Borch-Johnsen K, Frittitta L, Trischitta V, Pedersen O.
The K121Q variant of human PC‐1 gene is not associated with insulin resistance or type 2 diabetes among Danish Caucasians.
Diabetes.
2000;
49
1608-1611
28
Sbraccia P, Goodman P A, Maddux B A, Wong K Y, Chen Y D, Reaven G M, Goldfine I D.
Production of inhibitor of insulin-receptor tyrosine kinase in fibroblasts from patient with insulin resistance and NIDDM.
Diabetes.
1991;
40
295-299
29
Shao J, Catalano P M, Yamashita H, Ruyter I, Smith S, Youngren J, Friedman J E.
Decreased insulin receptor tyrosine kinase activity and plasma cell membrane glycoprotein-1 overexpression in skeletal muscle from obese woman with gestational diabetes mellitus (GDM): evidence for increased serine/threonine phosphorylation in pregnancy and GDM.
Diabetes.
2000;
49
603-610
31
Temple J K, Gardner R J, Robinson D O, Kilbirige M S, Ferguson A W, Baum J D, Barber J CK, James R S, Shield J PH.
Further evidence for imprinted gene for neonatal diabetes localized to chromosome 6q22-q23.
Hum Mol Genet.
1996;
5
1117-1121
33
UK Prospective Diabetes Study Group .
UK prospective diabetes study XII. Differences between Asian, Afro-Caribbean and white Caucasian type 2 diabetic patients at diagnosis of diabetes.
Diabet Med.
1994;
11
670-677
34
Wan S, Zhang T, Wang B, Han Y, Zhang C, Zhang Y, Gong H, Jin F, Wang L.
Obesity risk associated with the K121Q polymorphism of the glycoprotein PC‐1 gene.
Diabetes Obes Metab.
2006;
8
703-708