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.

clinical study of the unawareness of hypoglycemia type 1 diabetes

To investigate the relationship between awareness of symptoms and the autonomic reaction of hypoglycaemia, acute hypoglycaemia was induced with intravenous insulin [2.5 mu kg min.] in diabetic and non-diabetic subjects, all of whom had normal cardiovascular autonomic function tests. Three groups were studied: [1] nine patients with Type 1 diabetes with loss of awareness of hypoglycaemia; [2] eight patients who had normal awareness of hypoglycaemia, matched for duration of diabetes and blood glucose control; [3] eleven non-diabetic volunteers. The onset of the acute autonomic reaction was identified objectively by the sudden and rapid responses of heart rate and sweating. Hypoglycaemia symptom scores were estimated serially. Acute autonomic activation was observed to occur in all subjects in response to hypoglycaemia. In the [unaware] diabetic patients, onset of the reaction occurred at a significantly lower plasma glucose [1.0 +/- 0.1 mmol I] than in the [aware] diabetic patients [1.6 +/- 0.2 mmol 1] [p < 0.05] or in the non-diabetic control group 1.4 +/- 0.1 mmol l] [p < 0.05] Obvious neuroglycopenia was observed only in the [unaware] diabetic group and developed when plasma glucose had declined to approximately 1.4 +/- 0.1 mmol 1, and thus preceded the reaction [p< 0.02 vs the autonomic threshold]. Thus, the plasma glucose at which activation of the autonomic reaction was observed was lower in the diabetic patients with unawareness of hypoglycaemia

Hipoglicemia asociada con hiperplasia difusa de las células de los Islotes y bajo nivel de insulina

Un hombre de 87 años presentó hipoglicemia severa espontánea y su evaluación inicial no fue diagnosticá para exceso de insulina. Una extensa investigación no reveló tumor extrapancreatico. Después de ayuno prolongado, se encontró una elevación inapropiada de la insulina sérica inmunorreactiva (IIR). En la autopsia se confirmó la hiperplasia dufusa de células de los Islotes característica sugestiva de nesidioblastosis