Portal Branch Ligation-Induced Changes in Glucose Homeostasis and Hepatic Expression of Glucose-Regulating and -Utilising Proteins
Abstracts
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BACKGROUND: Liver resection for malignancies is limited by functional defiles. In the past years, preoperative portal vein embolization has been recognised as a useful technique to prevent postoperative liver failure by providing a preoperative hypertrophy of the future remnant liver. However, consequences in hepatic function have not yet been closely evaluated. AIMS: Changes in systemic glucose homeostasis and the hepatic mRNA-expression of Glucose-6-Phosphatase (G6P), Glyceraldehyd-6-Phosphate-Dehydrogenase (GAPDH) and Glucagon-Receptor (GR) were assessed in the rat models of partial hepatectomy (PH) and portal branch ligation (PBL), as well as after sham operation (SO). METHODS: 3 month old male Wistar rats were used. The expression levels of G6P, GAPDH and GR at different time points after surgery, beginning from 1 hour to 2 weeks, were determined using RT-PCR and Northern-Blotting techniques. Blood glucose levels were measured at the same time points. The experimental results of 4-6 animals were used under each experimental condition and at each time point. All parameters, were expressed by calculating the mean values and standard deviations and checked for significance using the unpaired student`s t-test. RESULTS: Systemic glucose levels decreased significantly following PH and, to a lesser extend, following PBL during the prereplicative period. The hepatic expression G6P, which regulates the release of glucose in the circulation, was up-regulated 1 hour after PH and PBL in both regenerative and regressive liver tissue. Thereafter, during the prereplicative period, the mRNA expression of G6P specifically decreased in the regenerating liver tissue, whereas it was again elevated during the replicative period. GR- and GAPDH-mRNA expression were contemporarily induced during the replicative period after PH and PBL in the regenerating lobes. CONCLUSIONS: These results show that compensatory regeneration after both PH and PBL is accomplished by transcriptional events in the expression of glucose regulating and -utilising proteins. Our results suggest that changes of systemic glucose levels following PH and PBL are controlled by a decrease in hepatic expression of G6P. These observations are important for the understanding of hepatic functional adaptations and glucose homeostasis under mitotic stimuli and might be of vital clinical relevance. |
