Tolbutamide inhibits gluconeogenesis in the tumor-influenced hepatocyte Journal Article
| Authors: | Blumberg, D.; Burt, M. E.; Kher, U.; Brennan, M. F. |
| Article Title: | Tolbutamide inhibits gluconeogenesis in the tumor-influenced hepatocyte |
| Abstract: | The tumor-bearing state is associated with an increase in gluconeogenesis which may contribute to the development of cancer cachexia. The purpose of this study was to determine if tolbutamide, a drug known to decrease gluconeogenesis in diabetes, could decrease gluconeogenesis in hepatocytes isolated from tumor-bearing rats. Hepatocytes from 24-hr fasted normal and methylcholanthrene-induced sarcoma-bearing rats (5-10% tumor burden) were isolated by in situ collagenase liver perfusion. Hepatocytes (n = 12 samples) from non-tumor-bearing (NTB) controls and tumor-bearing (TB) rats were incubated with lactate (10 mM) and alanine (10 mM) with and without 1 mM tolbutamide. Supernatant glucose concentration was measured at 30-min intervals for 2 hr. Rates of gluconeogenesis (± standard error) were calculated by linear regression and are expressed as nmole glucose/106 cells/min. Comparisons were made by two-way analysis of variance and significance defined as P < 0.05. TB hepatocytes had an increased rate of gluconeogenesis (P < 0.0001) from alanine and lactate (3.8 ± 0.30 and 2.2 ± 0.10, respectively) compared with NTB hepatocytes (0.66 ± 0.10 and 1.2 ± 0.04, respectively). TB hepatocytes treated with tolbutamide had a decreased (P < 0.0001) rate of gluconeogenesis from alanine and lactate (3.1 ± 0.10 and 1.1 ± 0.10, respectively) compared with untreated TB hepatocytes (5.3 ± 0.10 and 2.1 ± 0.10, respectively). Tolbutamide inhibits gluconeogenesis from lactate and alanine in tumor-influenced hepatocytes. © 1993 Academic Press. All rights reserved. |
| Keywords: | controlled study; drug efficacy; nonhuman; animal cell; animal; animal experiment; animal model; sarcoma; liver; drug mechanism; rat; glucose; rats; cachexia; neoplasm transplantation; alanine; liver cell; rats, inbred f344; lactic acid; sarcoma, experimental; gluconeogenesis; glycogen; methylcholanthrene; lactates; male; priority journal; article; tolbutamide |
| Journal Title: | Journal of Surgical Research |
| Volume: | 55 |
| Issue: | 5 |
| ISSN: | 0022-4804 |
| Publisher: | Academic Press Inc., Elsevier Science |
| Date Published: | 1993-11-01 |
| Start Page: | 565 |
| End Page: | 569 |
| Language: | English |
| DOI: | 10.1006/jsre.1993.1185 |
| PUBMED: | 8231177 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
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