A Population Association Study of Four Candidate Genes (Hexokinase II, Glucagon-like Peptide-1 Receptor, Fatty Acid Binding Protein-2, and Apolipoprotein C-II) with Type 2 Diabetes and Impaired Glucose Tolerance in Japanese Subjects

1996 ◽  
Vol 13 (10) ◽  
pp. 902-907 ◽  
Author(s):  
T. Yagi ◽  
S. Nishi ◽  
S-i. Hinata ◽  
M. Murakami ◽  
T. Yoshimi
2018 ◽  
Vol 64 (10) ◽  
pp. 1496-1504 ◽  
Author(s):  
Chi Ho Lee ◽  
Chloe Y Y Cheung ◽  
Yu Cho Woo ◽  
David T W Lui ◽  
Michele M A Yuen ◽  
...  

AbstractINTRODUCTIONRaised circulating adipocyte fatty acid–binding protein (AFABP) concentrations are associated with various adverse health conditions. However, their relationship with mortality remains to be defined, especially in view of the sexual dimorphism of circulating AFABP concentrations. Here we investigated prospectively whether serum AFABP concentrations predict multiple mortality outcomes in men and women alike, using a large clinic-based cohort of individuals with type 2 diabetes, a condition with raised AFABP concentrations.METHODSBaseline serum AFABP concentrations were measured in 5305 research participants with a monoclonal antibody-based sandwich immunoassay. The role of circulating AFABP concentrations in predicting mortality outcomes was evaluated by multivariable Cox regression analysis.RESULTSAmong the 5305 participants (59% men) in this study, over a median follow-up of 5 years, there were 512 deaths (19.3 deaths per 1000 person-years). Circulating AFABP concentrations, with higher levels in women at baseline, predicted all-cause mortality (P < 0.001), cardiovascular mortality (P = 0.037), and infection-related deaths (P < 0.002) among all participants. In sex-specific analyses, circulating AFABP concentration was an independent predictor of all-cause mortality in both men and women and a predictor of cancer-related deaths and infection-related deaths in men only. Furthermore, the addition of serum AFABP concentrations improved the time-dependent c statistics in predicting all-cause mortality in participants with type 2 diabetes (P = 0.008).CONCLUSIONSCirculating AFABP concentration was an independent predictor of various mortality outcomes in type 2 diabetes over and above known risk factors of reduced survival in men and women. The role of AFABP as a prognostic biomarker and therapeutic target warrants further investigation.


2017 ◽  
Vol 9 (4) ◽  
pp. 366-373 ◽  
Author(s):  
Hiroyuki Ito ◽  
Hitomi Yamashita ◽  
Mina Nakashima ◽  
Akifusa Takaki ◽  
Chiduko Yukawa ◽  
...  

Marine Drugs ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. 624 ◽  
Author(s):  
Giuseppe Floresta ◽  
Davide Gentile ◽  
Giancarlo Perrini ◽  
Vincenzo Patamia ◽  
Antonio Rescifina

Small molecule inhibitors of adipocyte fatty-acid binding protein 4 (FABP4) have received interest following the recent publication of their pharmacologically beneficial effects. Recently, it was revealed that FABP4 is an attractive molecular target for the treatment of type 2 diabetes, other metabolic diseases, and some type of cancers. In past years, hundreds of effective FABP4 inhibitors have been synthesized and discovered, but, unfortunately, none have reached the clinical research phase. The field of computer-aided drug design seems to be promising and useful for the identification of FABP4 inhibitors; hence, different structure- and ligand-based computational approaches have been used for their identification. In this paper, we searched for new potentially active FABP4 ligands in the Marine Natural Products (MNP) database. We retrieved 14,492 compounds from this database and filtered through them with a statistical and computational filter. Seven compounds were suggested by our methodology to possess a potential inhibitory activity upon FABP4 in the range of 97–331 nM. ADMET property prediction was performed to validate the hypothesis of the interaction with the intended target and to assess the drug-likeness of these derivatives. From these analyses, three molecules that are excellent candidates for becoming new drugs were found.


2019 ◽  
Vol 13 (3) ◽  
pp. 283
Author(s):  
Lili Huang ◽  
Weizhuo Dominique Tan ◽  
Chengjian Wang ◽  
Zhengxiang Huang ◽  
Johannes D. Veldhuis ◽  
...  

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 227 ◽  
Author(s):  
Marcin Trojnar ◽  
Jolanta Patro-Małysza ◽  
Żaneta Kimber-Trojnar ◽  
Bożena Leszczyńska-Gorzelak ◽  
Jerzy Mosiewicz

There is ample scientific evidence to suggest a link between the fatty acid-binding protein 4 (FABP4) and insulin resistance, gestational (GDM), and type 2 (T2DM) diabetes mellitus. This novel proinflammatory adipokine is engaged in the regulation of lipid metabolism at the cellular level. The molecule takes part in lipid oxidation, the regulation of transcription as well as the synthesis of membranes. An involvement of FABP4 in the pathogenesis of obesity and insulin resistance seems to be mediated via FABP4-dependent peroxisome proliferator-activated receptor γ (PPARγ) inhibition. A considerable number of studies have shown that plasma concentrations of FABP4 is increased in obesity and T2DM, and that circulating FABP4 levels are correlated with certain clinical parameters, such as body mass index, insulin resistance, and dyslipidemia. Since plasma-circulating FABP4 has the potential to modulate the function of several types of cells, it appears to be of extreme interest to try to develop potential therapeutic strategies targeting the pathogenesis of metabolic diseases in this respect. In this manuscript, representing a detailed review of the literature on FABP4 and the abovementioned metabolic disorders, various mechanisms of the interaction of FABP4 with insulin signaling pathways are thoroughly discussed. Clinical aspects of insulin resistance in diabetic patients, including women diagnosed with GDM, are analyzed as well.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Mei-Zhen Wu ◽  
Chi-Ho Lee ◽  
Yan Chen ◽  
Shuk-Yin Yu ◽  
Yu-Juan Yu ◽  
...  

Abstract Background The relationship between adipocyte fatty acid-binding protein (AFABP) and cardiac remodelling has been reported in cross-sectional studies, although with conflicting results. Type 2 diabetes mellitus (T2DM) is associated with left ventricular (LV) hypertrophy and diastolic dysfunction, as well as elevated circulating AFABP levels. Here we investigated prospectively the association between AFABP with the longitudinal changes of cardiac remodelling and diastolic dysfunction in T2DM. Methods Circulating AFABP levels were measured in 176 T2DM patients without cardiovascular diseases (CVD) at baseline. All participants received detailed transthoracic echocardiography both at baseline and after 1 year. Multivariable linear and Cox regression analyses were used to evaluate the associations of circulating AFABP levels with changes in echocardiography parameters and incident major adverse cardiovascular events (MACE), respectively. Results The median duration between baseline and follow-up echocardiography assessments was 28 months. Higher sex-specific AFABP quartiles at baseline were associated with increase in LV mass and worsening of average E/e′ (all P < 0.01). Multivariable linear regression demonstrated that AFABP in the highest quartile was independently associated with both increase in LV mass (β = 0.89, P < 0.01) and worsening of average E/e′ (β = 0.57, P < 0.05). Moreover, multivariable Cox regression analysis showed that elevated baseline circulating AFABP level independently predicted incident MACE (HR 2.65, 95% CI 1.16–6.05, P < 0.05) after adjustments for age, sex, body mass index, glycated haemoglobin, hypertension, dyslipidemia and presence of chronic kidney disease. Conclusion Circulating AFABP level at baseline predicted the development of LV hypertrophy, diastolic dysfunction and MACE in T2DM patients without CVD.


Sign in / Sign up

Export Citation Format

Share Document