Insulin receptors and renal sodium handling in hypertensive fructose-fed rats

Catena, Cristiana; Cavarape, Alessandro; Novello, Marileda; Giacchetti, Gilberta; Sechi, Leonardo A.

doi:10.1046/j.1523-1755.2003.00313.x

Cited by 91 publications

(83 citation statements)

References 35 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, there is some controversy about fructose-induced hypertension, mainly related to the potential to develop hypertension, and many potential explanations for the discrepancy in these findings have been offered, such as differences in the techniques used to measure BP and the feed or drinking conditions. 3,24 In particular, most studies have found that administering rats 10% fructose in drinking water induces a more severe metabolic disorder compared with providing 60% fructose in food. 22,24 In this study, we used 10% fructose in drinking water as a fructose-induced hypertension model.…”

Section: Discussionmentioning

confidence: 99%

“…The flexible catheter of the transmitter was surgically 36 secured in the abdominal aorta just below the renal arteries and pointed upstream (against the 37 flow), and the transmitter was sutured to the abdominal wall. The rats were housed in 38 3 individual cages following the operation. For data acquisition, each cage was placed over a 1 receiver panel, which was connected to the personal computer.…”

Section: Radio-telemetry Monitoring Of Blood Pressure 29mentioning

confidence: 99%

“…2 Some studies have shown that chronic fructose intake in normal rats induces hypertension in association with insulin resistance. 2,3 However, insulin infusion was found to stimulate local vasodilation by enhancing the action of nitric oxide (NO). 4 The effect of insulin on the baroreceptor reflex in nucleus tractus solitarii (NTS) is probably mediated by a change in sympathetic nervous activity.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Caffeine Intake Improves Fructose-Induced Hypertension and Insulin Resistance by Enhancing Central Insulin Signaling

et al. 2014

View full text Add to dashboard Cite

535I n humans, the intake of sugar-sweetened beverages is correlated with the prevalence of type 2 diabetes mellitus and obesity.1 High fructose intake is used as a well-established animal model for insulin resistance.2 Some studies have shown that chronic fructose intake in normal rats induces hypertension in association with insulin resistance.2,3 However, insulin infusion was found to stimulate local vasodilation by enhancing the action of nitric oxide (NO). 4 The effect of insulin on the baroreceptor reflex in nucleus tractus solitarii (NTS) is probably mediated by a change in sympathetic nervous activity. 4,5 Furthermore, sympathectomy can prevent the development of fructose-induced hypertension in rats. 6 Recent studies suggest that fructose consumption increases superoxide generation and attenuates baroreflex response. 7,8 Interestingly, inhibition of superoxide generation in NTS can reduce blood pressure (BP) in stroke-prone hypertensive rats. 9 The NTS is located in the dorsal medulla of the brain stem, which is the primary integrating center for cardiovascular regulation and other autonomic functions of the central nervous system. Furthermore, NO has important modulatory functions in the NTS, including the modulation of arterial BP and sympathetic nerve activity. 10 In previous experiments, we demonstrated that insulin microinjected into the NTS induces a depressor effect and initiates an interaction between insulin and phosphatidylinositol 3-kinase Abstract-Recent clinical studies found that fructose intake leads to insulin resistance and hypertension. Fructose consumption promotes protein fructosylation and formation of superoxide. In a previous study, we revealed that inhibition of superoxide production in the nucleus tractus solitarii (NTS) reduces blood pressure. Caffeine displays significant antioxidant ability in protecting membranes against oxidative damage and can lower the risk of insulin resistance. However, the mechanism through which caffeine improves fructose-induced insulin resistance is unclear. The aim of this study was to investigate whether caffeine consumption can abolish superoxide generation to enhance insulin signaling in the NTS, thereby reducing blood pressure in rats with fructose-induced hypertension. Treatment with caffeine for 4 weeks decreased blood pressure, serum fasting glucose, insulin, homeostatic model assessment-insulin resistance, and triglyceride levels and increased the serum direct high-density lipoprotein level in fructose-fed rats but not in control rats. Caffeine treatment resulted in the recovery of fructose-induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that caffeine reduced the fructoseinduced phosphorylation of insulin receptor substrate 1 (IRS1 S307) and reversed Akt S473 and neuronal nitric oxide synthase phosphorylation. Similarly, caffeine was able to improve insulin sensitivity and decrease insulin levels in the NTS evoked by fructose. Caffeine intake also reduced the production o...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Radio-telemetry Monitoring Of Blood Pressure 29mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Caffeine Intake Improves Fructose-Induced Hypertension and Insulin Resistance by Enhancing Central Insulin Signaling

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Moreover, IR phosphorylation in response to an acute insulin challenge might be a more sensitive test of IR signaling capacity in these rats. We have planned future studies using this approach to evaluate more comprehensively renal IR signaling Conversely, studies by Sechi BASIC RESEARCH www.jasn.org and associates 16 suggest that there is less insulin desensitization of the renal IR relative to other tissues. They examined the binding of labeled insulin, rather than solely expression, and concluded that there were no differences in IR number in the kidneys of fructosefed, insulin-resistant rats relative to controls.…”

Section: Discussionmentioning

confidence: 99%

Reduced Expression of Insulin Receptors in the Kidneys of Insulin-Resistant Rats

Tiwari¹,

Halagappa²,

Riazi³

et al. 2007

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Insulin resistance is accompanied by hyperinsulinemia and activation of the renin-angiotensin system, both of which are associated with hypertension. Because the kidney plays a major role in the regulation of blood pressure, we studied the regulation of insulin receptor expression in the kidney during states of insulin resistance. Using two rat models of insulin resistance, Western blot analysis demonstrated a significant reduction in the expression of insulin receptor subunits in the kidney compared to lean control rats. Treatment of insulin resistance in Zucker rats with the insulin-sensitizing drug rosiglitazone partially restored renal insulin receptor levels. Conversely, treatment with the angiotensin II type 1 receptor (AT1) antagonist candesartan increased renal insulin receptor expression compared to untreated rats. Streptozotocin-induced hyperglycemia, which results from hypoinsulinemia, reduced expression of renal insulin receptors. Hyperinsulinemia induced by insulin infusion, however, did not produce a similar effect. In conclusion, insulin receptors are downregulated in the kidneys of insulin resistant rats, possibly mediated by hyperglycemia and angiotensin II.

show abstract

“…Alternatively, the renal complications and local GH-IGF axis changes in type 2 diabetes mellitus may be affected to a greater degree by the local diabetic environment, which may lead to the upregulation of glucose transporters, such as solute carrier family 2 (facilitated glucose transporter), member 1 (previously known as GLUT1) [33], or the activation of the diacylglycerol-protein kinase C-extracellular signal-regulated kinase pathway by hyperglycaemia [34]. Possible interventions in this model could then include an improvement in renal insulin signalling [35,36]. This is exemplified by the use of insulin sensitisers in humans, such as peroxisome proliferator-activated receptor gamma agonists, which have been beneficial in the treatment of renal injury in early diabetic nephropathy [37,38].…”

Section: Discussionmentioning

confidence: 99%

Systemic and renal growth hormone–IGF1 axis involvement in a mouse model of type 2 diabetes

et al. 2007

View full text Add to dashboard Cite

Aims/hypothesis In previous studies we have shown a significant involvement of the growth hormone (GH)-IGF axis in animal models of type 1 diabetes mellitus, but the role of this endocrine system in type 2 diabetes mellitus is less well characterised. We therefore examined the endocrine and renal GH-IGF axis changes in db/db mice, a model of type 2 diabetes mellitus and nephropathy. Materials and methods Obese and lean animals were followed, beginning at hyperglycaemia onset, for 4 weeks. Albuminuria and creatinine clearance, as well as kidney and glomerular morphology were assessed. Tissue protein levels were determined by western blotting and mRNA levels by RT-PCR.Results Serum GH and IGF1 levels immediately prior to killing were decreased and liver mRNA levels of insulinlike growth factor binding protein 1 (Igfbp1) were increased in obese animals. Kidney weight was increased in obese animals, associated with hyperfiltration, albuminuria and glomerular hypertrophy. Administration of a somatostatin analogue (PTR-313) did not improve any of these parameters of diabetic renal involvement. Renal Igf1 mRNA was decreased and renal Igfbp1 mRNA and protein were significantly increased in obese animals. Renal insulindriven levels of phosphorylated forkhead box O1 (FOXO1) were decreased in obese animals. Conclusions/interpretation Diabetic db/db mice show significant renal changes (and IGFBP1 renal accumulation), similar to the findings in models of type 1 diabetes mellitus. A decreased signalling through the insulin receptor and decreased FOXO1 phosphorylation may allow Igfbp1 gene transcription. These renal changes are associated with low circulating IGF1 and GH levels and unchanged hepatic growth hormone receptor expression, unlike the condition in type 1 diabetes mellitus. This suggests that further GH inhibition to modulate renal complications in type 2 diabetes mellitus is not indicated.

show abstract

Insulin receptors and renal sodium handling in hypertensive fructose-fed rats

Cited by 91 publications

References 35 publications

Caffeine Intake Improves Fructose-Induced Hypertension and Insulin Resistance by Enhancing Central Insulin Signaling

Caffeine Intake Improves Fructose-Induced Hypertension and Insulin Resistance by Enhancing Central Insulin Signaling

Reduced Expression of Insulin Receptors in the Kidneys of Insulin-Resistant Rats

Systemic and renal growth hormone–IGF1 axis involvement in a mouse model of type 2 diabetes

Contact Info

Product

Resources

About