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Journal of Diabetes Research
Volume 2016, Article ID 8264830, 13 pages
Research Article

Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance

1Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan
2Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita 010-8543, Japan
3Chugai Research Institute for Medical Science, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan
4Project Planning & Coordination Department, Chugai Pharmaceutical Co., Ltd., 2-1-1 Nihonbashi, Muromachi, Chuo-ku, Tokyo 103-8324, Japan

Received 16 June 2015; Revised 26 September 2015; Accepted 29 September 2015

Academic Editor: Raffaella Mastrocola

Copyright © 2016 Atsunori Ueyama et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Supplementary Material

The Supplementary Material contains 3 supplemental tables and 6 figures showing additional data on the basic characteristics of RO5126766 and RO4987655 in Supplemental Table S1 and the following in vivo experiment results: From the first pharmacological evaluation of RO5126766 and RO498765 in db/db mice, Supplemental Tables S2 and S3 show the background blood chemical values after 17 days of treatment, and Supplemental Figure S1 shows the inhibition of ERK1/2 phosphorylation in peripheral blood mononuclear cells after 17 days of treatment. Supplemental Figure S2 shows antidiabetic effects of RO5126766 and RO4987655 in KK-Ay mice, and Supplemental Figure S3 shows changes in body weight induced by the treatment of pioglitazone in both db/db and KK-Ay mice. Additionally, Supplemental Figure S4 shows the effect of food restriction (70%) on blood glucose and glucose excursion during an oral glucose tolerance test (OGTT) in db/db mice. Finally, Supplemental Figure S5 shows the effects of RO5126766, RO4987655, and pioglitazone on the plasma insulin level during the OGTT, and Supplemental Figure S6 shows the adipogenic gene expression levels in epididymal adipose tissue in db/db mice.

  1. Supplementary Material