Binding of 125I-insulin to the isolated glomeruli of rat kidney.

Kurokawa, Kiyoshi; Silverblatt, Fredric J.; Klein, Keith L.; Wang, M S; Lerner, Roger L.

doi:10.1172/jci109592

Cited by 32 publications

(17 citation statements)

References 37 publications

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“…la). The time course of total binding was similar to that reported with isolated renal plasma membrane preparations [19,20] and in agreement with a recent study by Kurokawa et al [21] in isolated glomeruli. In con trast to total binding, nonspecific binding of l25I-insulin to isolated glomeruli reached a plateau by 10-20 min and amounted to about 25% of the total binding observed.…”

Section: Resultssupporting

confidence: 92%

Specific Insulin Receptors in Rat Renal Glomeruli

Meezan¹,

Freychet²

1980

Kidney Blood Press Res

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The kidney is a major site of pathologic complications in diabetes mellitus including those affecting the basement membrane. Although several hypotheses of the etiology of renal diabetic microangiopathy involve effects of insulin on basement membrane metabolism, little is known about the localization or properties of insulin receptors in isolated renal glomeruli. We have incubated isolated glomeruli and tubules with ¹²⁵I-insulin and examined the binding of the hormone to these purified renal subfractions. Glomeruli and tubules exhibited specific binding of ¹²⁵I-insulin at 22 °C which increased with time and protein concentration. Nonspecific binding accounted for 20–35% of the total binding observed. At a concentration of 1 ng/ml ¹²⁵I-insulin specific binding reached a plateau within 60–90 min at 22 °C. Unlabeled insulin competitively displaced ¹²⁵I-insulin from its binding sites with 2.8 × 10^-9 Minsulin inhibiting half of the initial binding to glomeruli while a 10-fold higher concentration of unlabeled insulin was required to achieve a similar inhibition of tubular binding. Insulin analogues were less potent than insulin itself in inhibiting the binding of ¹²⁵I-insulin to both glomeruli and tubules in the order of relative potency: insulin > despentapeptide insulin > proinsulin indicating the specificity of the binding. Scatchard analysis of the competition binding data of ¹²⁵I-insulin to glomeruli and tubules was consistent with two distinct binding sites and/or negative cooperativity between one class of receptor sites. The binding of ¹²⁵I-insulin to the glomerular receptor(s) exhibited a higher affinity than that to the tubular receptor(s) which had a greater binding capacity. These two subunits of the nephron, therefore, contain insulin receptors with different binding properties which may serve different functions.

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Section: Resultssupporting

confidence: 92%

Specific Insulin Receptors in Rat Renal Glomeruli

Meezan¹,

Freychet²

1980

Kidney Blood Press Res

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“…Indeed, NOS-2 (inducible) and NOS-3 (endothelial) are both expressed in endothelial and mesangial cells in the glomerular capillaries (16,45), and it has been shown that ANG II-mediated reduction in NO activity can reduce active capillary surface area (3). Insulin receptors are expressed in glomeruli (31) and are known to activate NOS (42). The insulin treatment in the present study could, therefore, have resulted in increased glomerular NO production, leading to mesangial cell relaxation and, therefore, increased K f .…”

Section: Discussionmentioning

confidence: 99%

Insulin induces the correlation between renal blood flow and glomerular filtration rate in diabetes: implications for mechanisms causing hyperfiltration

Pihl

Persson

Fasching

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Glomerular filtration rate (GFR) and renal blood flow (RBF) are normally kept constant via renal autoregulation. However, early diabetes results in increased GFR and the potential mechanisms are debated. Tubuloglomerular feedback (TGF) inactivation, with concomitantly increased RBF, is proposed but challenged by the finding of glomerular hyperfiltration in diabetic adenosine A(1) receptor-deficient mice, which lack TGF. Furthermore, we consistently find elevated GFR in diabetes with only minor changes in RBF. This may relate to the use of a lower streptozotocin dose, which produces a degree of hyperglycemia, which is manageable without supplemental suboptimal insulin administration, as has been used by other investigators. Therefore, we examined the relationship between RBF and GFR in diabetic rats with (diabetes + insulin) and without suboptimal insulin administration (untreated diabetes). As insulin can affect nitric oxide (NO) release, the role of NO was also investigated. GFR, RBF, and glomerular filtration pressures were measured. Dynamic RBF autoregulation was examined by transfer function analysis between arterial pressure and RBF. Both diabetic groups had increased GFR (+60-67%) and RBF (+20-23%) compared with controls. However, only the diabetes + insulin group displayed a correlation between GFR and RBF (R(2) = 0.81, P < 0.0001). Net filtration pressure was increased in untreated diabetes compared with both other groups. The difference between untreated and insulin-treated diabetic rats disappeared after administering N(ω)-nitro-l-arginine methyl ester to inhibit NO synthase and subsequent NO release. In conclusion, mechanisms causing diabetes-induced glomerular hyperfiltration are animal model-dependent. Supplemental insulin administration results in a RBF-dependent mechanism, whereas elevated GFR in untreated diabetes is mediated primarily by a tubular event. Insulin-induced NO release partially contributes to these differences.

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“…The (26). Alternatively, the glomerular hemodynamic effects of insulin deficiency could reflect altered production of vasoactive hormones within the kidney.…”

Section: Discussionmentioning

confidence: 99%

Control of glomerular hypertension by insulin administration in diabetic rats.

Scholey¹,

Meyer²

1989

J. Clin. Invest.

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Micropuncture studies were performed in Munich Wistar rats made diabetic with streptozotocin and in normal control rats. Diabetic rats received daily ultralente insulin to maintain moderate hyperglycemia (-300 mg/dl). Group 1 diabetic rats studied after routine micropuncture preparation exhibited elevation of the single nephron glomerular filtration rate (SNGFR) due to increases in the glomerular transcapillary hydraulic pressure difference and glomerular plasma flow rate. In group 2 diabetic rats infusion of insulin to achieve acute blood glucose control normalized the glomerular transcapillary pressure gradient while increasing the glomerular ultrafiltration coefficient, so that SNGFR remained elevated. Persistent elevation of SNGFR despite normalization of the transcapillary pressure gradient was also observed in group 3 diabetic rats infused with insulin plus sufficient dextrose to maintain hyperglycemia. These studies indicate that glomerular capillary hypertension in diabetes is an acutely reversible consequence of insulin deficiency and not the result of renal hypertrophy.

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Binding of 125I-insulin to the isolated glomeruli of rat kidney.

Cited by 32 publications

References 37 publications

Specific Insulin Receptors in Rat Renal Glomeruli

Specific Insulin Receptors in Rat Renal Glomeruli

Insulin induces the correlation between renal blood flow and glomerular filtration rate in diabetes: implications for mechanisms causing hyperfiltration

Control of glomerular hypertension by insulin administration in diabetic rats.

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