Effect of glucagon on protein synthesis in human rectal cancer in situ
Abstract
The purpose of this study was to determine the effect of glucagon or placebo on the rate of tumor fractional protein synthesis in situ in patients with localized rectal cancer who were not malnourished, demonstrated normal glucagon concentrations, and could therefore be used as a model to study the glucagon effect. Cancer cachexia is associated with an increased concentration of counterregulatory hormones, including glucagon. This altered hormonal milieu may not only contribute to malnutrition, but also promote tumor growth, because previous experimental work suggests that glucagon can cause human colorectal tumor cells to proliferate. Corresponding mechanisms in vivo have, thus far, not been investigated. Advanced mass spectrometry techniques (capillary gas chromatography [GC]/combustion isotope ratio mass spectrometry [IRMS]) were used to determine directly the incorporation rate of 1-[13C]-leucine into tissue protein. Because GC/IRMS requires only a small sample volume, three consecutive endoscopic biopsies could be obtained from the same tumor to determine isotopic enrichments at baseline, after a 4-hour glucagon infusion (3 ng/kg/min), or after placebo. In patients with localized rectal cancer, glucagon caused the tumor fr...Continue Reading
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