Regulation of liver and kidney glucose-6-phosphatase gene expression in hemorrhage and resuscitation

The authors have recently demonstrated that increased gene expression of gl ucose-6-phosphatase (Glu-6-Pase) in hemorrhagic hypotension (HH) and follow ing lactated Ringer's resuscitation (LR) is associated with a decrease in i nsulin and an increase in corticosterone concentrations. Objective: To eval uate the in-vivo role of hormones the authors used insulin (IN), phentolami ne and propranolol (PP) as an adrenergic blocker, and cyclic somatostatin ( CS) as a glucagon blocker to prevent the induction of Glu-6-Pase gene expre ssion in liver and kidney following HH and LR. Methods: Hemorrhage was indu ced in fasted anesthetized rats, and the reduction of blood pressure to 40 mm Hg for a duration of 30 minutes was accomplished by withdrawal or infusi on of shed blood. The resuscitated group underwent hemorrhage followed by f luid resuscitation with lactated Ringer's solution. Results: Neither PP nor CS treatment could block the induction of Glu-6-Pase messenger ribonucleic acid (mRNA) following either HH or LR. However, the administration of IN s ignificantly prevented the increase of Glu-6-Pase mRNA level and activity i n both liver and kidney following HH and LR. This was associated with a nor malization of plasma glucose, corticosterone, and glucagon levels and gluco se-6-phosphate concentrations in liver and kidney toward prehemorrhage leve ls. Conclusions: These results indicate that in-vivo treatment with insulin during hemorrhagic hypotension and resuscitation is capable of preventing the increase in Glu-6-Pase gene expression in liver and kidney responsible for the observed hyperglycemia.