Central action of insulin and the sympathetic nervous system on hepatic glucose production of conscious rats.

Author(s)

Izabela Martina Ramos Ribeiro de Toledo

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2012-04-04

Examining board members

Vagner Roberto Antunes; Kátia de Angelis Lobo D'Avila; Ubiratan Fabres Machado

• Advisor: Vagner Roberto Antunes

Abstract

Glucose is considered the most important fuel for the maintenance activities of the tissues. The liver is a key organ in maintaining glucose homeostasis and for this, requires the presence of hormones such as insulin that can perform its function by acting both peripherally and centrally. In addition, studies show that the autonomic nervous system (ANS) plays an extremely important role in glucose control. Therefore, the aim of this study was to evaluate the effect of insulin injected into the central nervous system on hepatic glucose production (HGP), and verifies the role of ANS in the modulation of this variable in conscious rats. For this, we used an animal model of sympathetic hyperactivity (SHR) and its control (Wistar). Preceding all experiments, the animals were kept in starvation for a period of 12 h. Insulin and / or denatured insulin (control vehicle) was injected into the lateral ventricle (LV) of the brain (100hU/ml) and HGP, MAP and HR were monitored at 2, 5, 10, 20 and 30 min. In the Wistar group we observed a maximal drop in PHG 10 min after microinjection of insulin in the VL (81.4 mg / dL) compared to baseline before insulin (110mg/dl) and the control group (insulin denatured) in the same time course (117.5 mg / dL). In another experimental group we found that antagonism of peripheral muscarinic receptors (methyl-atropine 2mg/kg, iv) was able to block the fall in HGP resulting from the action of insulin at the same time course (92mg/dL to 10\' vs 88mg / dL at baseline). On the other hand, the antagonism of peripheral adrenergic receptors (Phentolamine and propranolol 3mg/kg, 0.5 mg / kg, iv, respectively) did not affect the fall of HGP after administration of insulin in the VL. In the SHR group insulin injected into the VL did not promote changes in HGP in the times studied. The MAP and HR did not change after the central injection of insulin in both strains of animals. To evaluate the role of ANS on the baseline HGP independent of central action of insulin in both strains we performed the peripheral antagonism of adrenergic and muscarinic receptors and HGP was monitored at 2, 5, 10, 20, 30, 40, 50 and 60 min. The results showed that the adrenergic blockade reduced the HGP with a greater decrease at 40 min. both in Wistar (79 mg / dL, -25%) and in SHR (93 mg / dL, -22%) compared to baseline (Wistar: 106 mg / dL and SHR: 118 mg / dL). The blockade of peripheral muscarinic receptors did not alter the PHG in both strains. The set of results leads us to conclude that during starvation, the handle of the parasympathetic ANS is primarily responsible for the rapid drop in HGP caused by central action of insulin in Wistar. On the other hand, the autonomic sympathetic system plays a greater influence on the tonic baseline control of HGP than the parasympathetic system, independent of the central action of insulin in both SHR and Wistar. (AU)

• FAPESP's process: 09/13047-0 - Role of the autonomic nervous system in the hepatic production of glucose via central action of insulin in hypertensive animals
• Grantee: Izabela Martina Ramos Ribeiro de Toledo
• Support Opportunities: Scholarships in Brazil - Master