#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Relation between insulin secretion and action – study of genetic determination


Authors: Markéta Vaňková;  Petra Lukášová;  Olga Bradnová;  Josef Včelák;  Kateřina Dvořáková;  Běla Bendlová
Authors‘ workplace: Endokrinologický ústav Praha
Published in: Čas. Lék. čes. 2010; 149: 526-532
Category: Original Article

Overview

Background.
The disposition index represents insulin secretion related to the degree of insulin sensitivity, being constant for given degree of glucose tolerance. The aim of this study is to discern genetic determinants influencing the value of disposition index, e.g. predisposition to glucose intolerance.

Methods and Results.
Two hundred and four non-diabetic subjects with varied glucose tolerance were divided into groups according to the values of disposition index. Glucose and lipid metabolism, anthropometric parameters and family history of type 2 diabetes mellitus (DM2) were examined. The genotype frequency of candidate genes was compared between the groups of individuals within the lowest (Q1) and the highest (Q4) quartiles of the disposition index values. Those groups were not different concerning age and female to male ratio. Fasting and stimulated parameters of glucose metabolism and lipid profile were worse in group Q1 compared to group Q4. Group Q1 is characterized with higher number of individuals with metabolic syndrome and family history of DM2. The examination of candidate genes revealed the differences in genotype frequency of B2AR (rs1042714), PPARA (rs1800206), KCNJ11 (rs5219), and SLC30A8 (rs13266634) between groups Q1 and Q4.

Conclusions.
Low value of disposition index is related to the deterioration of glucose tolerance and other signs of metabolic syndrome. It is associated with genes affecting insulin secretion and genes related to energy metabolism and obesity.

Key words:
type 2 diabetes mellitus, disposition index, insulin sensitivity, insulin secretion, type 2 diabetes candidate genes.


Sources

1. Zeggini E, et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci bor type 2 diabetes. Nat Genet 2008; 40: 638–645.

2. Bendlova B, et al. Study of the genetic causes of polygeneticallv determined endocrinopathies-patience can bring success. Čas Lék čes 2007; 146: 198–204.

3. Rich SS, Bergman RN. The genetic basis of glucose homeostasis. Curr Diabetes Rev 2005; 1(3): 221–226.

4. Phillips DI, et al. Understanding oral glucose tolerance: comparision of glucose or insulin measurements during the oral glucose tolerance test šity specific measurements of insulin resistance and insulin secretion. Diabetic Medicine 1994; 11: 286–292.

5. Tura A, et al. Insulinogenic indices from insulin and C-peptide: comparison of beta-cell function from OGTT and IVGTT. Diabetes Res Clin pract 2006; 72: 298–301.

6. Kahn SE, et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 1993; 42: 1663–1672.

7. Bláha P. ANTROPO- ein Programm fur automatische Bearbeitung antropologischer Daten. Wiss. Zeitschrift der Humboldt-Universitat zu Berlin 1991; 5: 153–156.

8. Matsuda M, et al. Insulin sensitivity indices obtained from oral glucose testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462–1470.

9. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486–2497.

10. Bendlová B, Mazura I. Místo molekulární genetiky v endokrinologii. In: Stárka L. Aktuální endokrinologie. Praha: Maxdorf 1999; 42–52.

11. Bendlová B., Včelák J. DNA diagnostika. In: Kreze et al. Všeobecná a klinická endokrinológia. Bratislava: Academic Electronic Press 2004; 92–100.

12. Roden M. Clinical Diabetes Research: Methods and Techniques. Chichester: John Wiley & Sons 2007.

13. Pacini G, et al. Methods for clinical assessment of insulin sensitivity and ß-cell function. Best Pract Res Clin Endocrinol Metab 2003; 17: 305–322.

14. Aschner P. Metabolic syndrome as a risk factor for diabetes. Expert Rev Cardiovasc Ther 2010; 8(3):407–412.

15. Stumvoll M, Goldstein B, Van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet 2005; 365: 1333–1346.

16. Riedel MJ, et al. Current status of the E23K Kir6.2 polymorphism: implications for type-2 diabetes. Hum Genet 2005; 116: 133–145

17. Villareal DT, et al. Kir6.2 variant E23K increases ATP-sensitive K+ channel activity and is associated with impaired insulin release and enhanced insulin sensitivity in adults with normal glucose tolerance. Diabetes 2009; 58(8): 1869–1878.

18. Zeggini E, et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 2007; 316(5829): 1336–1341. Erratum in: Science 2007; 317(5841): 1035–1036.

19. Sladek R, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 2007; 445(7130): 881–885.

20. Scott LJ, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 2007; 316(5829): 1341–1345.

21. Large V, et al. Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function. J Clin Invest 1997; 100: 3005–3013.

22. Dallongeville J., et al. The gly16-arg16 and gln27-glu27 polymorphisms of beta-2-adrenergic receptor are associated with metabolic syndrome in men. J Clin Endocr Metab 2003; 88: 4862–4866.

23. Iwamoto N, et al. Gln27Glu beta2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver. Clin Chim Acta 2001; 314(1–2): 85–91.

24. Carlsson M, et al. Common variants in the beta2-(Gln27Glu) and beta3-(Trp64Arg)—adrenoceptor genes are associated with elevated serum NEFA concentrations and type II diabetes. Diabetologia 2001; 44(5): 629–636.

25. Gjesing AP, et al. Studies of the associations between functional beta2-adrenergic receptor variants and obesity, hypertension and type 2 diabetes in 7,808 white subjects. Diabetologia 2007; 50(3): 563–568.

26. Bossé Y, et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 2010; 42(7): 579–589.

27. Tai ES, et al. Polyunsaturated fatty acids interact with the PPARA-L162V polymorphism to affect plasma triglyceride and apolipoprotein C-III concentrations in the Framingham Heart Study. J Nutr 2005; 135(3): 397–403.

28. Andrulionyte L, et al. Single nucleotide polymorphisms of the peroxisome proliferator-activated receptor-alpha gene (PPARA) influence the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial. Diabetes 2007; 56(4): 1181–1186.

29. Silbernagel G, et al. The L162V polymorphism of the peroxisome proliferator activated receptor alpha gene (PPARA) is not associated with type 2 diabetes, BMI or body fat composition. Exp Clin Endocrinol Diabetes. 2009; 117(3): 113–118.

Labels
Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain management
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#