TCF7L2 correlation in both insulin secretion and postprandial insulin sensitivity

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art_FERREIRA_TCF7L2_correlation_in_both_insulin_secretion_and_postprandial_2018.PDF (915.34 KB)
Citações na Scopus
16
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
BIOMED CENTRAL LTD
Autores
FERREIRA, Mari Cassol
SILVA, Maria Elizabeth Rossi da
FUKUI, Rosa Tsuneshiro
ARRUDA-MARQUES, Maria do Carmo
SANTOS, Rosa Ferreira dos
Citação
DIABETOLOGY & METABOLIC SYNDROME, v.10, article ID 37, 7p, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: The TCF7L2 rs7903146 variant is strongly associated with type 2 diabetes mellitus (T2DM). However, the mechanisms involved in this association remain unknown and may include extrapancreatic effects. The aim of this study was to perform a metabolic characterization of T2DM patients with and without the TCF7L2 rs7903146 risk T allele and analyze some influences of the TCF7L2 genotype on glucose metabolism. Methods: Patients with T2DM (n = 162) were genotyped for the TCF7L2 rs7903146 single nucleotide polymorphism. Individuals with CT/TT and CC genotypes were compared regarding basal serum levels of glucose, glycosylated hemoglobin A1C, HDL, uric acid, insulin, and C-peptide. A subset of 56 individuals was evaluated during a 500-calorie mixed-meal test with measurements of glucose, insulin, proinsulin, C-peptide and glucagon. Additional secondary assessments included determination of insulinogenic index (IGI(30)), and insulin sensitivity (%S) and resistance (IR) by Homeostatic model assessment (HOMA). Results: Patients with the CT/TT genotype showed lower baseline plasma concentrations of C-peptide when compared with those with the CC genotype. Of the 56 individuals who participated in the mixed-meal test, 26 and 30 had the CC and CT/TT genotypes, respectively. CT/TT subjects, compared with CC individuals, had higher post prandial plasma levels of insulin and C-peptide at 30-120 min (p < 0.05) and proinsulin at 45-240 min (p < 0.05). Interestingly CT/TT individuals presented at baseline higher % S (p = 0.021), and lower IR (p = 0.020) than CC individuals. No significant differences in IGI(30) values were observed between groups. Conclusions: The T2DM individuals carrying the rs7903146 T allele of the TCF7L2 gene presented higher IR pattern in response to a mix-meal test, different of beta cell function at baseline assessed by C-peptide levels which was lower, and Homa-IR was lower when comparing with non-carriers.
Palavras-chave
Type 2 diabetes mellitus, Insulin resistance, Polymorphism, genetic, Polymorphism, single nucleotide, Glucose metabolism disorders, Hyperglycemia, postprandial
URI
https://observatorio.fm.usp.br/handle/OPI/27119
Referências
  1. Boj SF, 2012, CELL, V151, P1595, DOI 10.1016/j.cell.2012.10.053
  2. Bonora E, 2001, DIABETES CARE, V24, P2023, DOI 10.2337/diacare.24.12.2023
  3. Carr RD, 2008, AM J PHYSIOL-ENDOC M, V295, pE779, DOI 10.1152/ajpendo.90233.2008
  4. Cauchi S, 2007, J MOL MED, V85, P777, DOI 10.1007/s00109-007-0203-4
  5. Dahlgren A, 2007, DIABETOLOGIA, V50, P1852, DOI 10.1007/s00125-007-0746-5
  6. Damcott CM, 2006, DIABETES, V55, P2654, DOI 10.2337/db06-0338
  7. FALKO JM, 1975, J CLIN ENDOCR METAB, V41, P260, DOI 10.1210/jcem-41-2-260
  8. Grant SFA, 2006, NAT GENET, V38, P320, DOI 10.1038/ng1732
  9. Loos RJF, 2007, DIABETES, V56, P1943, DOI 10.2337/db07-0055
  10. Lyssenko V, 2007, J CLIN INVEST, V117, P2155, DOI 10.1172/JC130706
  11. Nobrega MA, 2013, DIABETES, V62, P706, DOI 10.2337/db12-1418
  12. Norton L, 2011, DIABETOLOGIA, V54, P3132, DOI 10.1007/s00125-011-2289-z
  13. Osmark P, 2009, DIABETOLOGIA, V52, P850, DOI 10.1007/s00125-009-1293-z
  14. Pilgaard K, 2009, DIABETOLOGIA, V52, P1298, DOI 10.1007/s00125-009-1307-x
  15. Poulsen P, 1999, DIABETOLOGIA, V42, P139, DOI 10.1007/s001250051131
  16. Savic D, 2011, GENOME RES, V21, P1417, DOI 10.1101/gr.123745.111
  17. Schafer SA, 2007, DIABETOLOGIA, V50, P2443, DOI 10.1007/s00125-007-0753-6
  18. Shah M, 2016, DIABETES, V65, P371, DOI 10.2337/db15-1233
  19. Stolerman ES, 2009, DIABETOLOGIA, V52, P614, DOI 10.1007/s00125-009-1266-2
  20. Vaag A, 1999, DAN MED BULL, V46, P197
  21. Wegner L, 2008, J CLIN ENDOCR METAB, V93, P4013, DOI 10.1210/jc.2008-0855
  22. Xavier GD, 2012, DIABETOLOGIA, V55, P2667, DOI 10.1007/s00125-012-2600-7

Coleções
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - LIM/18
Artigos e Materiais de Revistas Científicas - ODS/03