The role of genetic variation in TCF7L2 and KCNJ11, dietary intake, and physical activity on fasting plasma glucagon-like peptide-1 in male adolescents

  • Harry Freitag Luglio Department of Nutrition and Health, Universitas Gadjah Mada Medical School, Yogyakarta, Central Java http://orcid.org/0000-0001-5035-258X
  • Emy Huriyati Department of Nutrition and Health, Universitas Gadjah Mada Medical School, Yogyakarta, Central Java
Keywords: KCNJ11, TCF7L2, GLP-1, diet, physical activity

Abstract

Background Transcription factor 7-like 2 (TCF7L2) and potassium voltage-gated channel subfamily j member 11 (KCNJ11) gene polymorphisms have been associated with type 2 diabetes mellitus (T2DM) via regulation of insulin production. Ingested nutrients induce glucagon-like peptide-1 (GLP-1), which in turn induces insulin secretion.

Objective To evaluate the relationship between TCF7L2 and KCNJ11 gene polymorphism, dietary intake, and physical activity on fasting plasma GLP-1 in normal male adolescents.

Methods This observational study with a cross-sectional design included 54 male adolescents selected from high schools in Yogyakarta, Indonesia. Interviews were done to collect data on energy intake and physical activity. The GLP-1 and insulin levels were measured from fasting blood plasma. The TCF7L2 and KCNJ11 gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results Fasting GLP-1 was positively correlated with energy intake (r=0.276; P=0.047), but not with physical activity (r=0.011; P=0.936). The GLP-1 concentration was not associated with TCF7L2 and KCNJ11 gene polymorphisms (all P>0.05). In subjects with an EE genotype (KCNJ11), GLP-1 was not correlated with insulin (r=-0.036; P=0.435). However, in subjects with an EK genotype (KCNJ11), GLP-1 was positively correlated with insulin (r=0.394; P=0.026).

Conclusion GLP-1 concentration is positively correlated with body weight. Among male adolescents with a genetic variation in KCNJ11 (EK genotype), there is a significant correlation between GLP-1 and insulin signalling.

Author Biography

Harry Freitag Luglio, Department of Nutrition and Health, Universitas Gadjah Mada Medical School, Yogyakarta, Central Java
Department of Nutrition and Health

References

1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2012;35:64–71.
2. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047–53.
3. World Health Organization. Global Report on Diabetes. France: WHO Press; 2016.
4. Steinberger J, Moran A, Hong CP, Jacobs DR, Sinaiko AR. Adiposity in childhood predicts obesity and insulin resistance in young adulthood. J Pediatr. 2001;138:469–73.
5. Sinaiko AR, Steinberger J, Moran A, Prineas RJ, Vessby B, Basu S, et al. Relation of body mass index and insulin resistance to cardiovascular risk factors, inflammatory factors, and oxidative stress during adolescence. Circulation. 2005;111:1985–91.
6. Lee JM, Okumura MJ, Davis MM, Herman WH, Gurney JG. Prevalence and determinants of insulin resistance among U.S. adolescents: a population-based study. Diabetes Care. 2006;29:2427–32.
7. Muhammad HFL, Huriyati E, Susilowati R, Julia M. Magnesium intake and insulin resistance in obese adolescent girls. Paediatr Indones. 2009;49:200–4.
8. Golay A, Bobbioni E. The role of dietary fat in obesity. Int J Obes Relat Metab Disord. 1997;21 Suppl 3:S2–11.
9. Lau C, Faerch K, Glűmer C, Tetens I, Pedersen O, Carstensen B, et al. Dietary glycemic index, glycemic load, fiber, simple sugars, and insulin resistance: The Inter99 study. Diabetes Care. 2005;28:1397–403.
10. Liese AD, Schulz M, Fang F, Wolever TM, D'Agostino RB Jr, Sparks KC, et al. Dietary glycemic index and glycemic load, carbohydrate and fiber intake, and measures of insulin sensitivity, secretion, and adiposity in the Insulin Resistance Atherosclerosis Study. Diabetes Care. 2005;28:2832-8.
11. Ferrannini E, Natali A, Bell P, Cavallo-Perin P, Lalic N, Mingrone G. Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR). J Clin Invest. 1997;100:1166–73.
12. Karter AJ, D'Agostino RB Jr, Mayer-Davis EJ, Wagenknecht LE, Hanley AJ, Hamman RF, et al. Abdominal obesity predicts declining insulin sensitivity in non-obese normoglycaemics: The Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Obes Metab. 2005;7:230–8.
13. Weyer C, Hanson K, Bogardus C, Pratley RE. Long-term changes in insulin action and insulin secretion associated with gain, loss, regain and maintenance of body weight. Diabetologia. 2000;43:36–46.
14. Duval A, Busson-Leconiat M, Berger R, Hamelin R. Assignment of the TCF-4 gene (TCF7L2) to human chromosome band 10q25.3. Cytogenet Cell Genet. 2000;88:264–5.
15. Tong Y, Lin Y, Zhang Y, Yang J, Zhang Y, Liu H, et al. Association between TCF7L2 gene polymorphisms and susceptibility to type 2 diabetes mellitus: a large Human Genome Epidemiology (HuGE) review and meta-analysis. BMC Med Genet. 2009;10:15.
16. McTaggart JS, Clark RH, Ashcroft FM. The role of the KATP channel in glucose homeostasis in health and disease: more than meets the islet. J Physiol. 2010;588:3201–9.
17. Haghvirdizadeh P, Mohamed Z, Abdullah NA, Haghvirdizadeh P, Haerian MS, Haerian BS. KCNJ11 : genetic polymorphisms and risk of diabetes mellitus. J Diabetes Res. 2015;1–10.
18. Brubaker PL, Anini Y. Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2. Can J Physiol Pharmacol. 2003;81:1005–12.
19. Drucker DJ. Biological actions and therapeutic potential of the glucagon-like peptides. Gastroenterology. 2002;122:531–44.
20. MacDonald PE, El-Kholy W, Riedel MJ, Salapatek AM, Light PE, Wheeler MB. The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion. Diabetes. 2002;51:S434-42.
21. Holst JJ. Therapy of type 2 diabetes mellitus based on the actions of glucagon-like peptide-1. Diabetes Metab Res Rev. 2002;18:430–41.
22. Prunier C, Hocevar BA, Howe PH. Wnt signaling: physiology and pathology. Growth Factors. 2004;22:141–50.
23. Yi F, Brubaker PL, Jin T. TCF-4 mediates cell type-specific regulation of proglucagon gene expression by beta-catenin and glycogen synthase kinase-3beta. J Biol Chem. 2005;280:1457–64.
24. Hugill A, Shimomura K, Ashcroft FM, Cox RD. A mutation in KCNJ11 causing human hyperinsulinism (Y12X) results in a glucose-intolerant phenotype in the mouse. Diabetologia. 2010;53:2352–6.
25. World Health Organization. Growth reference 5-19 years. 2017 [cited 2017 October 4]. Available from http://www.who.int/growthref/en/.
26. Guedes DP, Lopes CC, Guedes JERP. Reproducibility and validity of the International Physical Activity Questionnaire in adolescents. Rev Bras Med Esporte 2005; 11;147-154.
27. Huriyati E, Luglio HF, Ratrikaningtyas PD, Tsani AFA, Sadewa AH, Juffrie, M. Dyslipidemia, insulin resistance and dietary fat intake in obese and normal weight adolescents: the role of uncoupling protein 2 -866G/A gene polymorphism. Int J Mol Epidemiol Genet. 2016;7:67–73.
28. Kreymann B, Williams G, Ghatei MA, Bloom SR. Glucagon-like peptide-1 7-36: a physiological incretin in man. Lancet. 1987;2:1300–4.
29. Toft-Nielsen MB, Madsbad S, Holst JJ. Determinants of the effectiveness of glucagon-like peptide-1 in type 2 diabetes. J Clin Endocrinol Metab. 2001;86:3853–60.
30. Nauck MA, Wollschläger D, Werner J, Holst JJ, Orskov C, Creutzfeldt W, et al. Effects of subcutaneous glucagon-like peptide 1 (GLP-1 [7-36 amide]) in patients with NIDDM. Diabetologia. 1996;39:1536-53.
31. Galindo Muñoz JS, Jimenez Rodríguez D, Hernandez Morante JJ. Diurnal rhythms of plasma GLP-1 levels in normal and overweight/obese subjects: lack of effect of weight loss. J Physiol Biochem. 2015;71:17–28.
32. Yamaoka-Tojo M, Tojo T, Takahira N, Matsunaga A, Aoyama N, Masuda T, et al. Elevated circulating levels of an incretin hormone, glucagon-like peptide-1, are associated with metabolic components in high-risk patients with cardiovascular disease. Cardiovasc Diabetol. 2010;9:17.
Published
2018-01-05
How to Cite
1.
Luglio H, Huriyati E. The role of genetic variation in TCF7L2 and KCNJ11, dietary intake, and physical activity on fasting plasma glucagon-like peptide-1 in male adolescents. PI [Internet]. 5Jan.2018 [cited 18Apr.2024];57(5):239-5. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/1516
Received 2017-06-10
Accepted 2017-10-16
Published 2018-01-05