Tolbutamide inhibits gluconeogenesis in the tumor-influenced hepatocyte.

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/10(6) 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.
AuthorsD Blumberg, M E Burt, U Kher, M F Brennan
JournalThe Journal of surgical research (J Surg Res) Vol. 55 Issue 5 Pg. 565-9 (Nov 1993) ISSN: 0022-4804 [Print] UNITED STATES
PMID8231177 (Publication Type: Journal Article)
Chemical References
  • Lactates
  • Lactic Acid
  • Methylcholanthrene
  • Tolbutamide
  • Alanine
  • Alanine (metabolism)
  • Animals
  • Gluconeogenesis (drug effects)
  • Lactates (metabolism)
  • Lactic Acid
  • Liver (drug effects, metabolism)
  • Male
  • Methylcholanthrene
  • Neoplasm Transplantation
  • Rats
  • Rats, Inbred F344
  • Sarcoma, Experimental (chemically induced, metabolism)
  • Tolbutamide (pharmacology)

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