THE METABOLIC EFFECTS OF POKEWEED MITOGEN IN MICE

Lectins are a family of proteins that stimulate cellular responses aft er binding to carbohydrate chains on plasma membranes. In the study de scribed here, a mixture of lectins-pokeweed mitogen (PKW)-was shown to have insulinomimetic effects in mice. After receiving PKW (15 mg/kg i ntraperitoneally [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% lo wer, 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, s howing that B and T lymphocytes were not required for the effects to d evelop. Cytokine antagonists attenuated the hypoglycemia and anorexia, but only by 50%. Further study showed that PKW has insulin-like effec ts in vitro. Glucose uptake was stimulated when murine C2C12 myotubes were exposed to an enriched fraction of PKW. These results demonstrate d 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. Co pyright (C) 1998 by W.B. Saunders Company.