TY - JOUR
T1 - Identification of circulating miR-101, miR-375 and miR-802 as biomarkers for type 2 diabetes
AU - Higuchi, Chigusa
AU - Nakatsuka, Atsuko
AU - Eguchi, Jun
AU - Teshigawara, Sanae
AU - Kanzaki, Motoko
AU - Katayama, Akihiro
AU - Yamaguchi, Satoshi
AU - Takahashi, Naoto
AU - Murakami, Kazutoshi
AU - Ogawa, Daisuke
AU - Sasaki, Sakiko
AU - Makino, Hirofumi
AU - Wada, Jun
N1 - Funding Information:
This work was supported by JSPS Grant-in-Aid for Scientific Research, grant numbers ( 25126716 , 25461354 , 26293218 , 26461361 , and 26461362 ).
Funding Information:
C.H., A.N., J.E., S.T., M.K., A.K., K.M., and S.S. have no conflicts of interest to declare. D.O. belongs to Department of Diabetic Nephropathy endowed by Boehringer Ingelheim and receives grant support from Eli Lilly. H.M. is a consultant for AbbVie, Astellas and Teijin, receives speaker honoraria from Astellas, Boehringer-Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Kyowa Hakko Kirin, MSD, Novartis, Pfizer, Takeda, and Tanabe Mitsubishi, and receives grant support from Astellas, Boehringer-Ingelheim, Daiichi Sankyo, Dainippon Sumitomo, Kyowa Hakko Kirin, Mochida, MSD, Novartis, Novo Nordisk, Pfizer, Takeda, and Tanabe Mitsubishi. J.W. is a consultant for Astellas and Boehringer Ingelheim, receives speaker honoraria from Novartis, Boehringer Ingelheim, and Novo Nordisk.
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Purpose The unique circulating microRNAs (miRNAs) observed in patients with type 2 diabetes (T2D) are candidates as new biomarkers and therapeutic targets. In order to identify circulating miRNAs relevant to the disease process in case of type 2 diabetes, we performed the Illumina sequencing of miRNAs derived from the serum, liver and epididymal white adipose tissue (WAT) of diet-induced obese male C57BL/6J mice. Basic Procedures We selected four miRNAs, miR-101, miR-335, miR-375, and miR-802, which are increased in the sera and tissues of obese mice, and measured the serum levels of miRNAs in T2D and subjects with normal glucose tolerance (NGT). Main Findings The serum concentrations of miRNAs, log10miR-101, log10miR-375, and log10miR-802, were significantly increased in the T2D patients compared with NGT subjects (1.41 ± 2.01 v.s. - 0.57 ± 1.05 (P = 1.36 × 10- 5), 0.20 ± 0.58 v.s. 0.038 ± 1.00 (P = 3.06 × 10- 6), and 2.45 ± 1.27 v.s. 0.97 ± 0.98 (P = 0.014), respectively). The log10miR-335 values did not demonstrate any significant differences between the T2D and NGT groups (- 1.08 ± 1.35 v.s. - 0.38 ± 1.21 (P = 0.25)). According to the stepwise regression analysis, the HbA1c was an independent predictor of miR-101. Regarding the serum miR-802 levels, eGFR, HbA1c and HDL-C values were identified as significant determinants. Principal Conclusions The present findings demonstrated that the circulating miR-101, miR-375 and miR-802 levels are significantly increased in T2D patients versus NGT subjects and they may become the new biomarkers for type 2 diabetes.
AB - Purpose The unique circulating microRNAs (miRNAs) observed in patients with type 2 diabetes (T2D) are candidates as new biomarkers and therapeutic targets. In order to identify circulating miRNAs relevant to the disease process in case of type 2 diabetes, we performed the Illumina sequencing of miRNAs derived from the serum, liver and epididymal white adipose tissue (WAT) of diet-induced obese male C57BL/6J mice. Basic Procedures We selected four miRNAs, miR-101, miR-335, miR-375, and miR-802, which are increased in the sera and tissues of obese mice, and measured the serum levels of miRNAs in T2D and subjects with normal glucose tolerance (NGT). Main Findings The serum concentrations of miRNAs, log10miR-101, log10miR-375, and log10miR-802, were significantly increased in the T2D patients compared with NGT subjects (1.41 ± 2.01 v.s. - 0.57 ± 1.05 (P = 1.36 × 10- 5), 0.20 ± 0.58 v.s. 0.038 ± 1.00 (P = 3.06 × 10- 6), and 2.45 ± 1.27 v.s. 0.97 ± 0.98 (P = 0.014), respectively). The log10miR-335 values did not demonstrate any significant differences between the T2D and NGT groups (- 1.08 ± 1.35 v.s. - 0.38 ± 1.21 (P = 0.25)). According to the stepwise regression analysis, the HbA1c was an independent predictor of miR-101. Regarding the serum miR-802 levels, eGFR, HbA1c and HDL-C values were identified as significant determinants. Principal Conclusions The present findings demonstrated that the circulating miR-101, miR-375 and miR-802 levels are significantly increased in T2D patients versus NGT subjects and they may become the new biomarkers for type 2 diabetes.
KW - Adipose tissues
KW - Diabetes
KW - Liver
KW - Serum
KW - miRNA
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U2 - 10.1016/j.metabol.2014.12.003
DO - 10.1016/j.metabol.2014.12.003
M3 - Article
C2 - 25726255
AN - SCOPUS:84923539215
SN - 0026-0495
VL - 64
SP - 489
EP - 497
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 4
ER -
