Investigation of central mechanism of insulin induced hypoglycemic convulsions in mice.
Insulin produces seizures in healthy and diabetic animals. Amongst suggested mechanisms, the role of neuromodulators and neurotransmitters is not clear. The present study explores the mechanisms involved in insulin-induced convulsions. Convulsions were induced in Swiss male albino mice with graded doses of insulin. Blood sugar levels were measured prior to and after the first convulsion. Drugs like 5-HTP (5-HT precursor), pCPA (5-HT depletor), ondansetron (5-HT3 antagonist), ketanserin (5-HT, antagonist), ketamine (NMDA antagonist), 1-dopa (dopamine precursor) and reserpine (amine depletor) were studied for interaction with convulsive behaviour induced by insulin. Insulin in 2 IU/kg dose did not produce convulsions while 4 and 8 IU/kg doses produced convulsions in 50% and 100% of animals respectively. 5-HTP, ondansetron, ketanserin, ketamine and l-dopa significantly protected/inhibited animals from convulsions at all studied doses of insulin. On the contrary, pCPA and reserpine potentiated insulin induced convulsions. Insulin caused mortality in 40 and 100% animals with 4 and 8 IU/kg doses respectively. pCPA and reserpine treatments caused mortality at all doses of insulin, while other drugs did not influence insulin induced mortality. Blood sugar levels were reduced in all groups irrespective of the presence or absence of convulsions. A definitive link of serotonergic, dopaminergic and excitatory amino acid pathways in mediating insulin-induced hypoglycemic convulsions is suggested.
Anuradha
K
K
Department of Pharmacology, Postgraduate Institute of Medical, Education & Research, Chandigarh 160 012, India.
Hota
D
D
Pandhi
P
P
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000378:metabolism; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism* / Q000401:mortality / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000633:toxicity*; D007328:Insulin / Q000633:toxicity*; D007649:Ketamine / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D012110:Reserpine / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000401:mortality / Q000517:prevention & control; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D015996:Survival Rate
D000927:Anticonvulsants; D000959:Antihypertensive Agents; D001786:Blood Glucose; D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D012702:Serotonin Antagonists; D012701:Serotonin; D007980:Levodopa; D007649:Ketamine; D012110:Reserpine; D007650:Ketanserin; D006916:5-Hydroxytryptophan; D004298:Dopamine