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Journal of Diabetes Research
Volume 2015, Article ID 497431, 12 pages
Research Article

Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities

1Department of Biochemistry, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea
2Department of Internal Medicine, School of Medicine, Konkuk University, Chungju Hospital, 82 Kukwondae-ro, Chungju 380-704, Republic of Korea
3Rmedica-Stem Cell, 98 Gasan Digital 2-ro, Geumcheon-gu, Seoul 153-768, Republic of Korea
4Department of Neurology, School of Medicine, Konkuk University, Chungju Hospital, 82 Kukwondae-ro, Chungju 380-704, Republic of Korea
5Department of Physiology, College of Medicine, Chung-Ang University, 84 Heukseouk-ro, Dongjak-gu, Seoul 156-861, Republic of Korea

Received 26 December 2014; Revised 11 March 2015; Accepted 31 March 2015

Academic Editor: Ponnusamy Saravanan

Copyright © 2015 Jun-Ho Lee 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.


Euglycemia is the ultimate goal in diabetes care to prevent complications. However, the benefits of euglycemia in type 2 diabetes are controversial because near-euglycemic subjects show higher mortality than moderately hyperglycemic subjects. We previously reported that euglycemic-diabetic rats on calorie-control lose a critical liver weight (LW) compared with hyperglycemic rats. Here, we elucidated the molecular mechanisms underlying the loss of LW in euglycemic-diabetic rats and identified a potential risk in achieving euglycemia by calorie-control. Sprague-Dawley diabetic rats generated by subtotal-pancreatectomy were fed a calorie-controlled diet for 7 weeks to achieve euglycemia using 19 kcal% (19R) or 6 kcal% (6R) protein-containing chow or fed ad libitum (19AL). The diet in both R groups was isocaloric/kg body weight to the sham-operated group (19S). Compared with 19S and hyperglycemic 19AL, both euglycemic R groups showed lower LWs, increased autophagy, and increased AMPK and caspase-3 and decreased mTOR activities. Though degree of insulin deficiency was similar among the diabetic rats, Akt activity was lower, and PTEN activity was higher in both R groups than in 19AL whose signaling patterns were similar to 19S. In conclusion, euglycemia achieved by calorie-control is deleterious in insulin deficiency due to increased autophagy and apoptosis in the liver via AMPK and caspase-3 activation.