The hyperinsulinemia produced by concanavalian A in rats is opioid-dependent and hormonally regulated

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 mug/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 percent (control: 10.2 + 0.9 mU/l and Con A-treated: 18.8 + 1 mU/l) compared to only 38 percent (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 mug/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 percent vs orchiectomized males: -5 + 3 percent; intact females: +86 + 23 percent vs ovariectomized females: -18 + 7.2 percent). Pretreating intact male and female rats with human chorionic gonadotropin also significantly inhibited the Con A-induced hyperinsulinemia. Estradiol (10 mug/kg, im) significantly blocked the Con A-induced increase in circulating insulin in male rats (101 + 17 percent for controls vs 32 + 5.3 percent for estradiol-treated animals, P<0.05) while testosterone (10 mg/kg, im) had no similar effect on intact female rats. Pretreating Con A-injected rats with opioid antagonists such as naloxone (1 mg/kg, sc) and naltrexone (5 mg/kg, sc) blocked the hyperinsulinemia produced by the lectin in males (control: +101 + 17 percent vs naloxone-treated: +5 + 14 percent, or naltrexone-treated: -23 + 45 percent) and females (control: +86 + 23 por cent vs naloxone-treated: +21 + 20 percent, or naltrexone-treated: -18 + 11 percent). These results demonstrate that Con A increases the levels of circulating insulin in rats and that this response is opioid-dependent and hormonally regulated.

Intracerebroventricular administration of canatoxin to rats increases the circulating levels of luteinizing hormone

Recent evidence has implicated the central nervous system as a target organ for canatoxin, a toxic protein present in Canavalia ensiformis seeds. This toxin activates the lipoxygenase pathway of arachidonic acid metabolism and can thus induce the release of substances mediated by lipoxygenase products. In the present study, the circulating levels of luteinizing hormone (LH) were measured by RIA in male Wistar rats (200-240 g) after the administration of canatoxin into the lateral cerebral ventricle. Canatoxin (0.5-2 micrograms in 2 microliters daily for 3 days) caused a dose- and time-dependent increase in the plasma levels of LH. The total dose of canatoxin used is subconvulsive. At 2, 4 and 24 h after 2 micrograms of canatoxin LH levels were increased by 10 per cent , 43 per cent and 61 per cent , respectively, compared to vehicle-injected animals (0.18 +/- 0.03 ng/ml). This response to 2 micrograms of canatoxin was not attenuated by pretreatment with two different lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA, 125 mg/kg) or esculetin (ECLT, 125 mg/kg), ip, 1 h before each canatoxin (CNTX) injection; per cent increase in LH with CNTX alone: 61 per cent ; CNTX+NDGA: 54 per cent ; CNTX+ECLT:76 per cent ; N = 5/group. These data show that intracerebral injection of CNTX in rats increases circulating levels of LH via a mechanism that is independent of the lipoxygenase pathway

Sex-related canatoxin-induced blood glucose alterations in the rat

The present study was designed to characterize sex-related canatoxin-induced blood glucose alterations in rats. Chronic administration of canatoxin (50 mU, ip, daily for 3 days) induced hypoglycemia in female rats (N = 6) (-36.54 + or - 3.24%, P<0.05). The response of pregnant rats (N = 8) was similar to that observed for male rats (+29.57 + or - 4.70%). Administration of canatoxin did not modify blood glucose levels of gonadectomized male or female rats. Similarly, pretreatment of intact male or female rats with human chorionic gonadotropin (40 IU/kg, im) blocked the effect of canatoxin on blood glucose levels. Gonadal steroid replacement (testosterone, 10 mg/kg,im) for gonadectomized male rats did not reverse the inhibition of canatoxin-induced blood glucose alterations, whereas pretreatment of intact female rats (N = 6) with tetosterone (10 mg/kg, im) significantly attenuated the canatoxin-induced hypoglycemia. These data indicate that the blood glucose alterations produced by canatoxin in rats are under hormonal regulation

Alterations in rat carbohydrate metabolism induced by canatoxin as a probable consequence of primary hypoxia

Canatoxin, a protein displaying lipoxygenase-activating properties isolated from Canavalia ensiformis seeds, induces hypoxia and hyperglycemia in male rats. Liver glycogen, blood glucose and lactate levesls were measured in male and female rats after canatoxin (50 mU, iv) injection. Increased levels of serum glutamic oxaloacetic transaminase activity were used as an indicator of hepatic injury. There was no sex-related difference observable during canatoxin-induced hypoxia but male and female rats did whow different patterns of metabolic change and hepatic injury after toxin observed in male rats while female rats showed only hypoglycemia and glycogenolysis. Pretreatment of male rats with either glucose, diazepam or hexamethonium abolished both the hypoxia and hepatic injury and the metabolic alterations produced by toxin injection. The results suggest that the metabolic alterations and hepatic injury detected after canatoxin injection may be a consequence of primary hypoxia

Convulsions induced by canatoxin in rats are probably a consequence of hypoxia

Canatoxin, a convulsant neurotoxin from the seeds of Canavalia ensiformis, induces lipoxygenase-dependent hypoxia and sex-related alterations of carbohydrate metabolism in rats which are blocked by glucose, diazepam and hexamethonium. The present study analyzes the possible causal relationship between the convulsant action of canatoxin and its effects on carbohydrate metabolism. The incidence of canatoxin-induced convulsions was greater in male than in female rats. Pretreatment of male rats with drugs that block hypoxia, such as glucose (2.5 g/kg,iv,15 min), diazepam (5 mg/kg,ip, at 48 h, 24 animals against convulsions, respiratory distress and death. These results suggest that canatoxin/induced convulsions are probably the consequence of hypoxia and both effects are mediated by lipoxygenase activation

Effect of canatoxin on the circulating levels of gonadotropins and prolactin in rats

1. The effects of canatoxin, the toxic principle from Canavalia ensiformis seeds which has lipoxygenase-activating properties, were evaluated in rats using radioimmunoassay techiniques to measure plasma levels of prolactin (PRL), progesterone, follicle stimulating (LH) and luteinizing (LH) hormones. 2. The chronic administration of canatoxin (50, 100 or 200 microng/Kg daily for 12 days, ip) to female rats induced a sharp rise in plasma LH and FSH concentrations whit no changes in progesterone level. A fall in circulating PRL was also observed. The frequency of proestrus and weight gain increased in rats treated with the higest dose of toxin used, but there was no alteration in weight of uterus or ovaries. 3. The increases in gonadotropin levels with canatoxin are consistent with the lipoxygenase-activating properties of the toxin, but do not explain why plasma PRL concentrations decreased in canatoxin-treated rats. 4. Since the animals in the control group had high PRL and low LH levels and since canatoxin increased LH and decreased PRL in the circulation, a possible stress-prevention effect is discussed for the toxin. 5. This study supports previous suggestions of central actions for canatoxin, and indicates the hypophysis and/or hypothalamus as one of the target sites for the toxin in the central nervous system