Identification of circulating miR-101, miR-375 and miR-802 as biomarkers for type 2 diabetes

Chigusa Higuchi, Atsuko Nakatsuka, Jun Eguchi, Sanae Teshigawara, Motoko Kanzaki, Akihiro Katayama, Satoshi Yamaguchi, Naoto Takahashi, Kazutoshi Murakami, Daisuke Ogawa, Sakiko Sasaki, Hirofumi Makino, Jun Wada

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)489-497
Number of pages9
JournalMetabolism: Clinical and Experimental
Volume64
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Type 2 Diabetes Mellitus
MicroRNAs
Biomarkers
Glucose
Serum
Obese Mice
White Adipose Tissue
Inbred C57BL Mouse
Regression Analysis
Diet
Liver

Keywords

  • Adipose tissues
  • Diabetes
  • Liver
  • miRNA
  • Serum

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Identification of circulating miR-101, miR-375 and miR-802 as biomarkers for type 2 diabetes. / Higuchi, Chigusa; Nakatsuka, Atsuko; Eguchi, Jun; Teshigawara, Sanae; Kanzaki, Motoko; Katayama, Akihiro; Yamaguchi, Satoshi; Takahashi, Naoto; Murakami, Kazutoshi; Ogawa, Daisuke; Sasaki, Sakiko; Makino, Hirofumi; Wada, Jun.

In: Metabolism: Clinical and Experimental, Vol. 64, No. 4, 01.04.2015, p. 489-497.

Research output: Contribution to journalArticle

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abstract = "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.",
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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

PY - 2015/4/1

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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 - miRNA

KW - Serum

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