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 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 caloriecontrolled 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. copyright © 2015 jun-ho lee et al.