The A98V Single Nucleotide Polymorphism (SNP) in Hepatic Nuclear Factor 1 α (HNF-1α) is Associated with Insulin Sensitivity and β-Cell Function

2008 ◽  
Vol 116 (S 01) ◽  
pp. S50-S55 ◽  
Author(s):  
A. Bergmann ◽  
J. Li ◽  
T. Selisko ◽  
M. Reimann ◽  
S. Fischer ◽  
...  
2016 ◽  
Vol 30 (1) ◽  
pp. 48-61 ◽  
Author(s):  
Makiko Fukaya ◽  
Caroline A. Brorsson ◽  
Kira Meyerovich ◽  
Leen Catrysse ◽  
Diane Delaroche ◽  
...  

Abstract Activation of the transcription factor nuclear factor kappa B (NFkB) contributes to β-cell death in type 1 diabetes (T1D). Genome-wide association studies have identified the gene TNF-induced protein 3 (TNFAIP3), encoding for the zinc finger protein A20, as a susceptibility locus for T1D. A20 restricts NF-κB signaling and has strong antiapoptotic activities in β-cells. Although the role of A20 on NF-κB inhibition is well characterized, its other antiapoptotic functions are largely unknown. By studying INS-1E cells and rat dispersed islet cells knocked down or overexpressing A20 and islets isolated from the β-cell-specific A20 knockout mice, we presently demonstrate that A20 has broader effects in β-cells that are not restricted to inhibition of NF-κB. These involves, suppression of the proapoptotic mitogen-activated protein kinase c-Jun N-terminal kinase (JNK), activation of survival signaling via v-akt murine thymoma viral oncogene homolog (Akt) and consequently inhibition of the intrinsic apoptotic pathway. Finally, in a cohort of T1D children, we observed that the risk allele of the rs2327832 single nucleotide polymorphism of TNFAIP3 predicted lower C-peptide and higher hemoglobin A1c (HbA1c) levels 12 months after disease onset, indicating reduced residual β-cell function and impaired glycemic control. In conclusion, our results indicate a critical role for A20 in the regulation of β-cell survival and unveil novel mechanisms by which A20 controls β-cell fate. Moreover, we identify the single nucleotide polymorphism rs2327832 of TNFAIP3 as a possible prognostic marker for diabetes outcome in children with T1D.


Obesity ◽  
2021 ◽  
Author(s):  
Anny H. Xiang ◽  
Mayra P. Martinez ◽  
Enrique Trigo ◽  
Kristina M. Utzschneider ◽  
Melanie Cree‐Green ◽  
...  

2019 ◽  
Vol 21 (1) ◽  
pp. 18-27
Author(s):  
Joon Young Kim ◽  
Hala Tfayli ◽  
Fida Bacha ◽  
SoJung Lee ◽  
Sara F. Michaliszyn ◽  
...  

Diabetes Care ◽  
2016 ◽  
Vol 40 (1) ◽  
pp. 85-93 ◽  
Author(s):  
Silva Arslanian ◽  
Laure El ghormli ◽  
Fida Bacha ◽  
Sonia Caprio ◽  
Robin Goland ◽  
...  

1998 ◽  
Vol 83 (2) ◽  
pp. 503-508
Author(s):  
Victor C. Pardini ◽  
Ivana M. N. Victória ◽  
Selma M. V. Rocha ◽  
Danielle G. Andrade ◽  
Aline M. Rocha ◽  
...  

Lipoatropic diabetes (LD) designates a group of syndromes characterized by diabetes mellitus with marked insulin resistance and either a localized or generalized absence of adipose tissue. In this study, we evaluated plasma leptin levels in subjects with congenital generalized lipoatropic diabetes (CGLD, n = 11) or acquired generalized lipoatropic diabetes (AGLD, n = 11), and assessed correlations between leptin levels and estimations of insulin secretion and insulin sensitivity using homeostasis model assessment (HOMA). Leptin levels were 0.86 ± 0.32, 1.76 ± 0.78, and 6.9 ± 4.4 ng/mL in subjects with CGLD, AGLD, and controls (n = 19), respectively (ANOVA P < 0.0001). Specific insulin levels were 154 ± 172, 177 ± 137 and 43 ± 22 pmol/L, respectively (P < 0.0001). Insulin sensitivity was significantly decreased in both groups with LD (P< 0.0001), whereas HOMA β-cell function was not significantly different when compared with controls. Leptin levels were significantly correlated with body mass index, insulin levels, and HOMA β-cell function, and inversely correlated with insulin sensitivity in control subjects but not in subjects with generalized LD. In conclusion, decreased leptin levels were observed in subjects with generalized LD, with a trend towards lower levels in the acquired than in the congenital form (P = 0.06). The temporal relationship between the decrease in leptin levels and the development of lipoatrophy should be investigated in at-risk young relatives of subjects with the acquired forms to assess the usefulness of leptin levels as a marker of lipoatrophy.


2008 ◽  
Vol 88 (3) ◽  
pp. 638-644 ◽  
Author(s):  
Sergio López ◽  
Beatriz Bermúdez ◽  
Yolanda M Pacheco ◽  
José Villar ◽  
Rocío Abia ◽  
...  

2000 ◽  
Vol 50 ◽  
pp. 68
Author(s):  
M. Albareda ◽  
J. Rodríguez-Espinosa ◽  
M. Moruño ◽  
A. de Leiva ◽  
R. Corcoy

Sign in / Sign up

Export Citation Format

Share Document