The Effect Of Insulin Induced Acute Hypoglycemia on Brain Neurotransmitters and Oxidative Stress , Possible Protection by Gabapentin And Olanzapine

  • Hadaf A. ALJunaiyeh Assistant Professor, Department Of Pharmacology, College Of Medicine, University of Thi-Qar, Iraq.
  • Alaa Kadhem Alwan B.Sc. (Pharmacy), Thi-Qar Health Office, Republic of Iraq.
  • Nabeel A. J. Ali Professor , Department Of Pharmacology, College Of Medicine, University of Basrah, Iraq.
Keywords: Hypoglycemia, Insulin, Gabapentin, Olanzapine, MDA, Dopamine, GABA, Noradrenaline


Background, Diabetes mellitus is one of the most common metabolic diseases in the world and the number of its patients still growing and according to the International Diabetes Federation reach 552 in 2030. Hypoglycemia is dangerous adverse effect of insulin therapy and remains an unsolved problem; During hypoglycemia lack of glucose supply to neurons can lead to confusion, seizures, brain damage which is sometimes irreversible and can even cause death. Aim ,The study designed to test the effect of acute insulin induced hypoglycemia on: 1)the brain oxidative status as measured by Malondialdehyde (MDA). 2)brain neurotransmitters; dopamine, ɣ-Amino butyric acid (GABA)and noradrenaline. And Possible protective effect of gabapentin and olanzapine against hypoglycemia. Method and Materials, 32 male rabbits, randomly divided into four groups, group A (control group) treated with (2.5ml/kg) distilled water orally and (0.1 ml/kg) distilled water subcutaneously. Group B (Hypoglycemic group) treated with (2.5ml/kg) distilled water orally and (1 IU/kg) insulin subcutaneously. Group C (hypoglycemic group + gabapentin) given (25 mg/kg) gabapentin orally and (1 IU/kg) insulin subcutaneously. Group D (hypoglycemic group + olanzapine) treated with(2mg/kg) olanzapine orally and (1 IU /kg) insulin subcutaneously. Blood samples  used to determine glucose level and brain tissue used to estimation neurotransmitters. Statistics, Results are presented as the mean ± Sd. Statistical significance was set at P < 0.05 and determined by the (SPSS) version 22. Data were analyzed by one-way ANOVA and unpaired t-test. Results, Insulin treated group show significantly increased of MDA and noradrenaline in comparison to control group. In (insulin + gabapentin) treated group show significant decreased of dopamine and no significant changes of GABA and noradrenaline in comparison to control group. While (insulin + olanzapine) result was significantly increased of MDA and decreased of both dopamine and GABA in comparison to control group. On other side the use of gabapentin with insulin lead significant decreased of  MDA and dopamine, significantly decreased of noradrenalin and  Significant decreased of  glucose levels at day one 10 AM, in comparison to use insulin only. While addition olanzapine to insulin show the following result no significantly increased of  MDA, Significant decrease of dopamine and GABA and No significant decreased of noradrenaline in comparison to use insulin only. Conclusion, Insulin hypoglycemia lead to oxidative stress and brain neurotransmitters disturbance which are partly reversed by gabapentin and olanzapine, on the other hand both drugs tend to exacerbate insulin induced hypoglycemia. Caution should be excreted when giving any of the two drugs in such situation.


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