concanavalin-a and Hyperinsulinism

The present study examines the effect of concanavalin A (Con A) on the blood insulin and glucose levels of rats. Male and female rats treated with Con A (62.5-500 micrograms/kg) for three days showed a dose- and time-dependent hyperinsulinemia that lasted more than 48 h. Male rats were more sensitive to Con A. Thus, 6 h after treatment with Con A the circulating insulin levels in male rats had increased by 85% (control: 10.2 +/- 0.9 mU/l and Con A-treated: 18.8 +/- 1 mU/l) compared to only 38% (control: 7.5 +/- 0.2 mU/l; Con A-treated: 10.3 +/- mU/l) in females. An identical response was seen after 12 h. Con A (250 micrograms/kg) produced time-dependent hypoglycemia in both sexes but more pronounced in males. There was no correlation between the hypoglycemia and hyperinsulinemia described above. The Con A-induced hyperinsulinemia in rats of both sexes was abolished in gonadectomized animals (intact males: +101 +/- 17% vs orchiectomized males: -5 +/- 3%; intact females: +86 +/- 23% vs ovariectomized females: -18 +/- 7.2%). Pretreating intact male and female rats with human chorionic gonadotropin also significantly inhibited the Con A-induced hyperinsulinemia. Estradiol (10 micrograms/kg,i.m.) significantly blocked the Con A-induced increase in circulating insulin in male rats (101 +/- 17% for controls vs 32 +/- 5.3% for estradiol-treated animals, P < 0.05) while testosterone (10 mg/kg, i.m.) had no similar effect on intact female rats. Pretreating Con A-injected rats with opioid antagonists such as naloxone (1 mg/kg, s.c.) and naltrexone (5 mg/kg, s.c.) blocked the hyperinsulinemia produced by the lectin in males (control: +101 +/- 17% vs naloxone-treated: +5 +/- 14%, or naltrexone-treated: -23 +/- 4.5%) and females (control: +86 +/- 23% vs naloxone-treated: +21 +/- 20%, or naltrexone-treated: -18 +/- 11%). These results demonstrate that Con A increases the levels of circulating insulin in rats and that this response is opioid-dependent and hormonally regulated.

Topics: Animals; Blood Glucose; Castration; Concanavalin A; Female; Hormones; Hyperinsulinism; Insulin; Male; Narcotic Antagonists; Rats; Rats, Wistar; Time Factors

We studied the effects of anti-CD2 monoclonal antibodies (MAb) on spontaneous and induced autoimmune diabetes mellitus in diabetes-prone (DP) and diabetes-resistant (DR) BB/Wor rats. In DP rats, all anti-CD2 MAb prevented spontaneous diabetes and the adoptive transfer of diabetes with Con-A--stimulated acute diabetic spleen cells; OX34 prevented Poly I:C induced accelerated onset of diabetes and the adoptive transfer of diabetes with Con-A--stimulated RT6.1+ T cell depleted DR splenocytes. In DP rats, all anti-CD2 MAb except OX53 depleted CD4+ T cells, without depleting natural killer cells or CD8+ T cells. OX34 injected DR rats were profoundly depleted of CD4+ T cells without evidence of decreased CD8+ T cells, but were not protected against the induction of diabetes by RT6.1+ T-cell depletion and Poly I:C injections. We conclude that anti-CD2 MAbs protect against BB/Wor autoimmune diabetes by depleting CD4+ T cells, preventing the activation of effector cells, or by blocking CD2/ligand interaction between effector and target cells.

Topics: Animals; Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Autoimmune Diseases; CD2 Antigens; CD4 Antigens; CD8 Antigens; Concanavalin A; Diabetes Mellitus, Type 1; Flow Cytometry; Hyperinsulinism; Immunotherapy, Adoptive; Injections; Lymph Nodes; Poly I-C; Rats; Rats, Inbred BB; Receptors, Immunologic; Spleen; T-Lymphocytes

Topics: Animals; Concanavalin A; Culture Techniques; Cyclic AMP; Diazoxide; Homeostasis; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Liver; Lymphocytes; Obesity; Rats; Receptor, Insulin