Subdiaphragmatic vagus nerve activity and hepatic venous glucose are differentially regulated by the central actions of insulin in Wistar and SHR

Abstract

Glucose is the most important energy substrate for the maintenance of tissues function. The liver plays an essential role in the control of glucose production, since it is able to synthesize, store, and release glucose into the circulation under different situations. Hormones like insulin and catecholamines influence hepatic glucose production (HGP), but little is known about the role of the central actions of physiological doses of insulin in modulating HGP via the autonomic nervous system in nonanesthetized rats especially in SHR where we see a high degree of insulin resistance and metabolic dysfunction. Wistar and SHR received ICV injection of insulin (100 nU/μL) and hepatic venous glucose concentration (HVGC) was monitored for 30 min, as an indirect measure of HGP. At 10 min after insulin injection, HVGC decreased by 27% in Wistar rats, with a negligible change (3%) in SHR. Pretreatment with atropine totally blocked the reduction in HVGC, while pretreatment with propranolol and phentolamine induced a decrease of 8% in HVGC after ICV insulin injection in Wistar. Intracarotid infusion of insulin caused a significant increase in subdiaphragmatic vagus nerve (SVN) activity in Wistar (12 ± 2%), with negligible effects on the lumbar splanchnic sympathetic nerve (LSSN) activity (−6 ± 3%). No change was observed in SVN (−2 ± 2%) and LSSN activities (2 ± 3%) in SHR after ICA insulin infusion. Taken together, these results show, in nonanesthetized animals, the importance of the parasympathetic nervous system in controlling HVGC, and subdiaphragmatic nerve activity following central administration of insulin; a mechanism that is impaired in the SHR.

Exercise Training Improves the Altered Renin‐Angiotensin System in the Rostral Ventrolateral Medulla of Hypertensive Rats

“…The rats were implanted with unilateral guide cannula (21 gauges) for ICV injections of drugs, which was described previously [ 35 , 36 ]. Coordinates for lateral ventricle injections (−1.0 mm to Bregma; 1.5 mm lateral to midline; and −4.5 mm to the surface of the skull) were based on the rat atlas of Paxinos and Watson [ 37 ].…”

Estudos anatomo-funcionais de vias integrativas hipotalâmicas e bulbares envolvidas no controle do sistema nervoso autônomo decorrentes da ação central da insulina.

“…Hormones such as insulin and catecholamines influence PHG but little is known about the physiological centrally acting insulin doses in modulating PHG through SNA rats unanesthetized especially in SHR has the characteristic of insulin resistance among other metabolic disorders. Previous studies from our laboratory showed a 27% decrease in blood glucose measured directly into the hepatic vein (CGVH) Wistar rats already at 10 minutes after insulin ICV injection (100 nU / ml) without significant changes (3%) in SHR ( Ribeiro et al, 2015). The pre-treatment with atropine methyl-CGVH completely blocked the reduction, whereas pretreatment with propranolol and phentolamine induced a decrease of 8% by CGVH insulin after ICV injection in Wistar rats.…”

“…Hormônios como insulina e catecolaminas influenciam a PHG mas pouco se conhece acerca da ação central de doses fisiológicas de insulina na modulação da PHG através do SNA em ratos não anestesiados especialmente em SHR que tem como característica resistência à insulina dentre outras disfunções metabólicas. Estudos anteriores do nosso laboratório mostraram uma diminuição de 27% na glicemia medida diretamente na veia hepática (CGVH) de ratos Wistar já ao 10 minutos após a injeção ICV de insulina (100 nU /mL) sem alterações significantes (3%) em SHR (Ribeiro et al, 2015). O pré-tratamento com metil-atropina bloqueou totalmente a redução CGVH, enquanto que o pré-tratamento com propranolol e fentolamina induziu uma diminuição de 8% em CGVH após injeção ICV de insulina em ratos Wistar.…”

“…No sistema nervoso central (SNC) a insulina desempenha uma série de funções, tais como aprendizado, memória, assim como na regulação da homeostase energética (Plum et al, 2006). De particular interesse a insulina exerce uma importante ação no hipotálamo suprimindo a liberação de glicose pelo fígado como já demonstrado pelo nosso laboratório (Ribeiro et al, 2015). (Szabo et al, 1983;Obici et al, 2002;Pocai et al, 2005).…”

Afferent vs. efferent cervical vagal nerve stimulation

“…In the liver, efferent activation of the vagus nerve promotes the formation of glycogen by activating glycogen synthetase (48). Parasympathetic innervation of the liver also reduces hepatic glucose release (41). These two mechanisms can function to reduce glucose concentrations in the blood.…”