We have isolated a stable, transplantable, and small
glucagonoma (MSL-G-AN) associated with abrupt onset of severe
anorexia occurring 2-3 wk after subcutaneous
transplantation. Before onset of
anorexia, food consumption is comparable to untreated controls.
Anorexia is followed by adipsia and
weight loss, and progresses rapidly in severity, eventually resulting in reduction of food and water intake of 100 and 80%, respectively. During the
anorectic phase, the rats eventually become
hypoglycemic and hypothermic. The
tumor-associated
anorexia shows no sex difference, and is not affected by bilateral abdominal
vagotomy, indicating a direct central effect. The adipose satiety factor
leptin, known to suppress food intake by reducing hypothalamic
neuropeptide Y (NPY) levels, was not found to be expressed by the
tumor, and circulating
leptin levels were reduced twofold in the
anorectic phase. A highly significant increase in hypothalamic (arcuate nucleus) NPY
mRNA levels was found in
anorectic rats compared with control animals. Since elevated hypothalamic NPY is among the most potent stimulators of feeding and a characteristic of most animal models of
hyperphagia, we conclude that the MSL-G-AN
glucagonoma releases circulating factor(s) that overrides the hypothalamic NPY-ergic system, thereby eliminating the orexigenic effect of NPY. We hypothesize a possible central role of
proglucagon-derived
peptides in the observed
anorexia.