Effect of intracerebroventricularly injected insulin on urinary sodium excretion by cerebroventricular streptozotocin-treated rats

Abstract

Recent evidence suggests that insulin may influence many brain functions. It is known that intracerebroventricular (icv) injection of nondiabetogenic doses of streptozotocin (STZ) can damage insulin receptor signal transduction. In the present study, we examined the functional damage to the brain insulin receptors on central mechanisms regulating glomerular filtration rate and urinary sodium excretion, over four periods of 30 min, in response to 3 µl insulin or 0.15 NaCl (vehicle) injected icv in STZ-treated freely moving WistarHannover rats (250-300 g). The icv cannula site was visually confirmed by 2% Evans blue infusion. Centrally administered insulin (42.0 ng/µl) increased the urinary output of sodium (from 855.6 ± 85.1 to 2055 ± 310.6 ∆%/min; N = 11) and potassium (from 460.4 ± 100 to 669 ± 60.8 ∆%/min; N = 11). The urinary sodium excretion response to icv insulin microinjection was markedly attenuated by previous central STZ (100 µg/3 µl) administration (from 628 ± 45.8 to 617 ± 87.6 ∆%/min; N = 5) or by icv injection of a dopamine antagonist, haloperidol (4 µg/3 µl) (from 498 ± 39.4 to 517 ± 73.2 ∆%/min; N = 5). Additionally, insulin-induced natriuresis occurred by increased post-proximal tubule sodium rejection, despite an unchanged glomerular filtration rate. Excluding the possibility of a direct action of STZ on central insulin receptor-carrying neurons, the current data suggest that the insulin-sensitive response may be processed through dopaminergic D1 receptors containing neuronal pathways. Correspondence

Intranasal insulin reverts central pathology and cognitive impairment in diabetic mother offspring

“…Both female and male offspring from diabetic and control mothers were randomly divided and sacrified immediately after birth or at P7. A set of animals received unilateral ICV insulin (ICV-Ins) injection at P7 [ 12 , 13 ]. Briefly, mice were anesthetized with isoflurane (Astrazeneca, Spain) and placed in a sterotaxic device (David-Kopf Instruments, Tujunga, CA, USA).…”

Consequences of cerebroventricular insulin injection on renal sodium handling in rats: effect of inhibition of central nitric oxide synthase

“…We have shown that acute icv insulin microinjection in rats promotes a dose-dependent increase in sodium excretion, followed by a post-proximal sodium excretion (17,18,29). Conversely, intravenous hyperinsulinemic euglycemic clamp and oral glucose test in humans and rats lead to antinatriuresis (30,31).…”

“…Although it has been shown that the peripheral action of insulin reduces urinary sodium excretion, suggesting an attractive reciprocal link between the renal effect of insulin, urinary sodium excre-www.bjournal.com.br Braz J Med Biol Res 42 (12) 2009 tion and the development or maintenance of hypertension, studies have indicated that acute intracerebroventricular (icv) insulin injection significantly decreases both blood pressure and heart rate, with corresponding decreases in renal sympathetic nerve activity in anesthetized rats (15,16). Our laboratory recently showed that centrally administered insulin produced a dose-related increase in the urinary output of sodium, which was abolished by bilateral renal denervation (17) and cerebroventricular streptozotocin administration in rats (18) and that the response was significantly enhanced in long-term icv insulin-pretreated animals compared to control (19). On the other hand, Shankar et al (20) have reported that acute systemic administration of high doses of N Gmonomethyl-L-arginine, a competitive inhibitor of nitric oxide (NO) synthase, results in marked insulin resistance, hyperglycemia, defective insulin secretion, and hypertension.…”

Efeito da administração intracerebroventricular de insulina sobre a excreção urinaria de sodio e vias de sinalização da insulina em hipotalamo de ratos hipertensos

“…A administração aguda intracerebroventricular de insulina promove aumento da excreção urinária de sódio em animais, efeito abolido pela denervação renal, tratamento com streptozotocina e L-NAME, enfatizando a ação da insulina no sistema nervoso central na homeostasia do sódio, bem como a necessidade de eferências renais íntegras, integridade dos receptores de insulina e do sistema do óxido nítrico para a promoção dos efeitos assinalados (AGARWALA e BAPAT 1977;MICHELLOTTO, CARVALHEIRA et al 2002;MACEDO, FURLAN et al 2003;FURLAN, MARSHALL et al 2003).…”