Intranasal Delivery of Insulin Effectively Modulates Hepatic Glucose Production in Dexamethasone-induced Insulin Resistance

[Speaker] Anoka A Njan:1
[Co-author] Chloe Fatigun:1, A Alli-Oluwafuyi:1, Olufunke Olorundare:1
1:Dept. of Pharmacology and Therapeutics, University of Ilorin, Nigeria

Insulin resistance is one of the hallmarks of type 2 diabetes mellitus. Dexamethasone (Dex) induces hyperglycemia by enhancing hepatic glucose production and reducing insulin sensitivity. This study evaluates the effect of 2 IU intranasal insulin (INI) on peripheral blood glucose profile in dexamethasone-treated Wister rats. In the first phase of the study, 13 animals were grouped into 2 groups and administered either vehicle (0.9% Normal saline, 20micro;L) or insulin intranasally to assess acute effects of intranasal insulin on peripheral glucose and brain hormones. The second phase involved administration of either intranasal insulin or vehicle to control or dexamethasone (0.5mg/kg, IP) treated animals for seven days. Glucose, insulin and lipid metabolites were assayed from serum while hepatic gluconeogenic enzyme activity - glucokinase and glucose-6-phosphatase (G6Pase) and lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G6PDH) were assayed from liver and brain homogenates respectively. Intranasal insulin lowered blood glucose at the 3rd hour and elevated brain insulin. Dex-induced hyperglycemia was associated with increased glucose-6-phosphatase activity and decreased high-density lipoprotein (HDL), effects attenuated by (INI) administration, the anti-hyperglycemic effects of intranasal insulin may be due to its inhibitory effect on gluconeogenic G6Pase in dexamethasone treated Wistar rats. Also INI did not induce oxidative stress in the brain which suggests no brain damage during the period of study.
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