The metabolic effects of pokeweed mitogen in mice

Lectins are a family of proteins that stimulate cellular responses after binding to carbohydrate chains on plasma membranes. In the study described here, a mixture of lectins--pokeweed mitogen (PKW)--was shown to have insulinomimetic effects in mice. After receiving PKW (15 mg/kg intraperitoneally [IP]), serum glucose declined from 154 +/- 3 to 23 +/- 10 mg/dL by 24 hours later. Anorexia developed, and by 3 days, there was a significant decline in body weight. Carcass weights were 10% lower, and epididymal fat pad weights were 45% lower. When given for 16 days, PKW 3 mg/kg every other day caused a sustained 10% weight loss. Severe combined immune deficiency (SCID) mice were sensitive to PKW, showing that B and T lymphocytes were not required for the effects to develop. Cytokine antagonists attenuated the hypoglycemia and anorexia, but only by 50%. Further study showed that PKW has insulin-like effects in vitro. Glucose uptake was stimulated when murine C2C12 myotubes were exposed to an enriched fraction of PKW. These results demonstrated that PKW has both insulin-like activity and weight-reducing effects when administered to mice. The development of therapy for adult-onset diabetes or obesity based on lectins from pokeweed may be possible.