Table of Contents Author Guidelines Submit a Manuscript
International Journal of Endocrinology
Volume 2015, Article ID 406394, 9 pages
http://dx.doi.org/10.1155/2015/406394
Research Article

Effect of Repetitive Glucose Spike and Hypoglycaemia on Atherosclerosis and Death Rate in Apo E-Deficient Mice

1Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
2Center for Molecular Diabetology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
3Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan
4Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
5Sportology Center, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan

Received 12 June 2015; Revised 31 July 2015; Accepted 9 August 2015

Academic Editor: Marco Bugliani

Copyright © 2015 Kenichi Nakajima 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.

Abstract

Epidemiological data suggest that postprandial hyperglycaemia and hypoglycaemia are potential risk factors for cardiovascular disease. However, the effects of repetitive postprandial glucose spikes, repetitive hypoglycaemia, and their combination on the progression of atherosclerosis remain largely unknown. The present study investigated the effects of rapid rises and falls in glucose, and their combination, on the progression of atherosclerosis in apolipoprotein (apo) E-deficient mice. In this study, apo E-deficient mice with forced oral administration of glucose twice daily for 15 weeks were used as a model of repetitive postprandial glucose spikes, and apo E-deficient mice given an intraperitoneal injection of insulin once a week for 15 weeks were used as a model of repetitive hypoglycaemia. In addition, we established a model of both repetitive postprandial glucose spikes and hypoglycaemia by combining the above interventions. Atherosclerosis was evaluated in all mice by oil red O staining. Administration of ipragliflozin, a selective inhibitor of sodium-glucose cotransporter 2, in the mouse model of repetitive glucose spikes inhibited the progression of atherosclerosis, whereas long-term repetitive glucose spikes, repetitive hypoglycaemia, and their combination had no significant impact on atherosclerosis. However, repetitive hypoglycaemia was associated with poor survival rate. The results showed that repetitive hypoglycaemia reduces the survival rate without associated progression of atherosclerosis in apo E-deficient mice.