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Blood glucose alterations induced in rats by canatoxin, a protein isolated from jack bean (Canavalia ensiformis)
Abstract:
Canatoxin, a lethal convulsant protein isolated from the seeds of Canatoxin ensiformis (jack bean), induced a biphasic alteration in blood glucose levels when injected i.v. into rats and mice. After administration of subconvulsant doses of canatoxin the rats showed initially hyperglycemia during the first 30 min, followed by a long-lasting hypoglycemia. Return to basal glucose levels was not seen up to 15 days. The hyperglycemic effect was dose-dependent and occurred in starved and well-fed animals. A parallelism between convulsant and hyperglycemic activity was observed throughout all canatoxin purification steps. Mice were about 20-fold less sensitive (on a weight basis) than rats to canatoxin-induced hyperglycemia. The hyperglycemic phase was not affected by pretreatment of the rats with alpha- or beta-adrenergic blockers or chlorpromazine, but was potentiated by reserpine and haloperidol. Diazepam and hexamethonium were able to block the hyperglycemic phase of canatoxin's effect. The results suggest that the hyperglycemic alterations induced by canatoxin in rats and mice are probably mediated via the central nervous system.
Insights
Canatoxin, a protein from jack bean, causes initial hyperglycemia followed by prolonged hypoglycemia in rats and mice. These blood glucose changes are likely mediated by the central nervous system.
Area of Science:
- Toxicology
- Neuropharmacology
- Endocrinology
Background:
- Canatoxin is a lethal convulsant protein from Canavalia ensiformis (jack bean).
- Its effects on physiological parameters, particularly blood glucose, are not fully understood.
Purpose of the Study:
- To investigate the effects of Canatoxin on blood glucose levels in rats and mice.
- To explore the potential mechanisms underlying Canatoxin-induced glycemic alterations.
Main Methods:
- Intravenous injection of Canatoxin into rats and mice.
- Administration of subconvulsant doses to observe biphasic blood glucose changes.
- Use of various pharmacological agents (adrenergic blockers, diazepam, etc.) to probe the mechanism.
Main Results:
- Canatoxin induced a biphasic effect: initial hyperglycemia followed by long-lasting hypoglycemia in rats.
- The hyperglycemic effect was dose-dependent and occurred in both starved and fed animals.
- Mice showed significantly lower sensitivity to Canatoxin's hyperglycemic effects compared to rats.
- Diazepam and hexamethonium blocked the hyperglycemic phase, while reserpine and haloperidol potentiated it.
Conclusions:
- Canatoxin significantly alters blood glucose levels in rodents, inducing a unique biphasic response.
- The observed glycemic alterations are likely mediated through the central nervous system.
- Pharmacological interventions suggest a complex interplay of neurotransmitter systems in Canatoxin's action.