Amelioration of glucose homeostasis by glycyrrhizic acid through gluconeogenesis rate-limiting enzymes

The activities of phosphoenolpyruvate carboxykinase (PEPCK) are influenced by active glucocorticoids which are activated by 11-beta-hydroxysteroid dehydrogenase 1 (11 beta-HSD1) while hexose-6-phosphate dehydrogenase (H6PDH) influences the activities of 11-beta HSD1 in a cofactor manner. Dysregulation of PEPCK and H6PDH has been associated with the pathogenesis of metabolic syndrome. Sixteen male Sprague Dawley rats, fed ad libitum, were assigned to two groups, control and treated, with the treated group being given GA at 100 mg/kg for one week. Blood and subcutaneous and visceral adipose tissue, abdominal and quadriceps femoris muscle, liver and kidney were examined. GA treatment led to an overall significant decrease in blood glucose while HOMA-IR. PEPCK activities decreased in the liver but increased in the visceral adipose tissue. H6PDH activities also decreased significantly in the liver while 11 beta-HSD1 activities decreased significantly in all studied tissues except for subcutaneous adipose tissue. Adipocytes in the subcutaneous and visceral depots showed a reduction in size. Though increased glycogen storage was seen in the liver, no changes were observed in the kidneys and muscles. Results from this study may imply that GA could counteract the development of type 2 diabetes mellitus by improving insulin sensitivity and probably by reduction of H6PDH, 11 beta-HSD1 and a selective decrease in PEPCK activities. (C) 2011 Elsevier B. V. All rights reserved.