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.
abstract: 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.
authors.affiliation: Department of Biochemistry, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, School of Medicine, Konkuk University, Chungju Hospital, 82 Kukwondae-ro, Chungju 380-704, Republic of Korea.
authors.forename: Soo-Bong
authors.initials: SB
authors.lastname: Choi
authors.affiliation: Department of Biochemistry, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Mingli
authors.initials: M
authors.lastname: Jin
authors.affiliation: Department of Biochemistry, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea ; Rmedica-Stem Cell, 98 Gasan Digital 2-ro, Geumcheon-gu, Seoul 153-768, Republic of Korea.
authors.forename: Ju-Han
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Neurology, School of Medicine, Konkuk University, Chungju Hospital, 82 Kukwondae-ro, Chungju 380-704, Republic of Korea.
authors.forename: Sang-Don
authors.initials: SD
authors.lastname: Han
authors.affiliation: Department of Physiology, College of Medicine, Chung-Ang University, 84 Heukseouk-ro, Dongjak-gu, Seoul 156-861, Republic of Korea.
authors.forename: Hyemi
authors.initials: H
authors.lastname: Bae
authors.affiliation: Department of Physiology, College of Medicine, Chung-Ang University, 84 Heukseouk-ro, Dongjak-gu, Seoul 156-861, Republic of Korea.
authors.forename: Inja
authors.initials: I
authors.lastname: Lim
authors.affiliation: Department of Biochemistry, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Noh
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009929:Organ Size; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase; D053148:Caspase 3