Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities
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 c...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/497431 |
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| author | Jun-Ho Lee Soo-Bong Choi Mingli Jin Ju-Han Lee Sang-Don Han Hyemi Bae Inja Lim Yun-Hee Noh |
| author_facet | Jun-Ho Lee Soo-Bong Choi Mingli Jin Ju-Han Lee Sang-Don Han Hyemi Bae Inja Lim Yun-Hee Noh |
| author_sort | Jun-Ho Lee |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5ebdaa95174147e8b45ace896a134708 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-5ebdaa95174147e8b45ace896a1347082025-08-20T03:34:33ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/497431497431Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR ActivitiesJun-Ho Lee0Soo-Bong Choi1Mingli Jin2Ju-Han Lee3Sang-Don Han4Hyemi Bae5Inja Lim6Yun-Hee Noh7Department of Biochemistry, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of KoreaDepartment of Internal Medicine, School of Medicine, Konkuk University, Chungju Hospital, 82 Kukwondae-ro, Chungju 380-704, Republic of KoreaDepartment of Biochemistry, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of KoreaDepartment of Biochemistry, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of KoreaDepartment of Neurology, School of Medicine, Konkuk University, Chungju Hospital, 82 Kukwondae-ro, Chungju 380-704, Republic of KoreaDepartment of Physiology, College of Medicine, Chung-Ang University, 84 Heukseouk-ro, Dongjak-gu, Seoul 156-861, Republic of KoreaDepartment of Physiology, College of Medicine, Chung-Ang University, 84 Heukseouk-ro, Dongjak-gu, Seoul 156-861, Republic of KoreaDepartment of Biochemistry, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of KoreaEuglycemia 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.http://dx.doi.org/10.1155/2015/497431 |
| spellingShingle | Jun-Ho Lee Soo-Bong Choi Mingli Jin Ju-Han Lee Sang-Don Han Hyemi Bae Inja Lim Yun-Hee Noh Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities Journal of Diabetes Research |
| title | Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities |
| title_full | Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities |
| title_fullStr | Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities |
| title_full_unstemmed | Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities |
| title_short | Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities |
| title_sort | euglycemia in diabetic rats leads to reduced liver weight via increased autophagy and apoptosis through increased ampk and caspase 3 and decreased mtor activities |
| url | http://dx.doi.org/10.1155/2015/497431 |
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