The binding and degradation of 125I-labelled insulin by rat kidney brush-border membranes

Thomas, J. Hywel; Jenkins, C.D.G.; Davey, Philip; Papachristodoulou, Despina K.

doi:10.1016/0020-711x(83)90100-3

Cited by 8 publications

(5 citation statements)

References 28 publications

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“…However, here we demonstrate a direct effect on the phospholipid metabolism, possibly mediated by active insulin receptors. This finding would suggest one metabolic role for papillary insulin receptors, which differs from the insulin degradating role attributed to the renal cortex receptors (Kurokawa et al 1979;Meezan and Freychet 1982;Talor, Emmanouel and Katz 1982;Thomas et al 1983;Meezan, Pillion and Elgavish 1988;Rabkin, Ryan and Duckworth 1984). The precise biochemical pathway by which insulin exerted its effect cannot be elucidated from these results.…”

Section: Discussionmentioning

confidence: 91%

“…The presence of specific high-affinity insulin receptors in both isolated renal glomeruli and tubules has been demonstrated (Kurokawa, Silverblatt, Klein, Wang and Lemer 1979;Meezan and Freychet 1982). Subsequently, it has been reported that purified renal tubular brush border and basolateral membrane have insulin receptors with similar binding properties (Talor, Emmanouel and Katz 1982;Thomas, Jenkins, Davey and Papachristodoulou 1983). More recently, it has been reported that insulin association with isolated renal brush border membrane vesicles almost totally represents low-affinity, high-capacity binding sites (Meezan, Pillion and Elgavish 1988).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, it has been suggested that the effect of insulin on electrolyte transport occurred in the distal nephron (De Fronzo, Cooke, Andreas, Faloona and Davis 1975). However, insulin receptors have been described only in renal cortex glomeruli and proximal convoluted tubules (Kurokawa et al 1979;Meezan and Freychet 1982;Talor, Emmanouel and Katz 1982;Thomas et al 1983;Meezan, Pillion and Elgavish 1988;Rabkin, Ryan and Duckworth 1984). No information is available on insulin receptors in other zones of the kidney.…”

Section: Introductionmentioning

confidence: 99%

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Specific and Functional Insulin Receptors in Rat Renal Papilla

Balbis¹,

Setton-Avruj²,

Nb³

et al. 1993

Horm Metab Res

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To investigate a possible action of insulin on the rat kidney papilla, the binding of 125I-insulin to papilla microsomes was examined. This binding was specific to insulin in that it was displaced by increasing concentrations of unlabelled porcine insulin and to a lesser extent by porcine proinsulin and IGF-I, but not by IGF-II and bGH. Scatchard plot of the binding data was curvilinear consistent with either two classes of receptors with different affinities or a single class of receptors that showed negative cooperativity. A small fraction of 125I-insulin (maximum 2%) was degraded during incubation, but with a Km two order of magnitude higher than the constant of affinity for binding. Insulin stimulates the incorporation of phosphate to phosphatidylcholine in a dose-dependent manner, reaching a maximum with 10 nM insulin. This data showed both the presence of specific insulin receptors in the kidney papilla and an insulin action through the synthesis of phospholipids by insulin.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Specific and Functional Insulin Receptors in Rat Renal Papilla

Balbis¹,

Setton-Avruj²,

Nb³

et al. 1993

Horm Metab Res

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“…Luminal membranes degrade insulin at twice the rate that the contraluminal membranes do, and contain several peptidases, including a neutral metalloendopeptidase which degrades the isolated B chain of insulin but not intact insulin [31,55]. The isolated luminal membrane does not contain GIT activity [30] and does not produce intact A chains from insulin [20,58]. Thus, as a result of interacting with luminal membranes, insulin may be degraded by the membrane-associated neutral metalloendopeptidase, which, in concert with insulin protease, degrades insulin synergistically to trichloroacetic-acid-soluble products [31,55].…”

Section: Enzymatic Mechanisms Of Renal Insulin Degradationmentioning

confidence: 99%

“…Together, GIT and lysosomal proteases could catalyze the initial, specific and later, non-specific steps, respectively, of insulin degradation by proximal tubular cells. However, several studies have presented evidence that GIT plays, at best, a minor role in renal insulin degradation [2,30,58].…”

Section: Enzymatic Mechanisms Of Renal Insulin Degradationmentioning

confidence: 99%

The renal metabolism of insulin

1984

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The kidney plays a pivotal role in the clearance and degradation of circulating insulin and is also an important site of insulin action. The kidney clears insulin via two distinct routes. The first route entails glomerular filtration and subsequent luminal reabsorption of insulin by proximal tubular cells by means of endocytosis. The second involves diffusion of insulin from peritubular capillaries and subsequent binding of insulin to the contraluminal membranes of tubular cells, especially those lining the distal half of the nephron. Insulin delivered to the latter sites stimulates several important processes, including reabsorption of sodium, phosphate, and glucose. In contrast, insulin delivered to proximal tubular cells is degraded to oligopeptides and amino-acids by one of two poorly delineated enzymatic pathways. One pathway probably involves the sequential action of insulin protease and either GIT or non-specific proteases; the other probably involves the sequential action of GIT and lysosomal proteases. The products of insulin degradation are reabsorbed into the peritubular capillaries, apparently via simple diffusion. Impairment of the renal clearance of insulin prolongs the half-life of circulating insulin by a number of mechanisms and often results in a decrease in the insulin requirement of diabetic patients. Much needs to be learned about these metabolic events at the subcellular level and how they are affected by disease states. Owing to the heterogeneity of cell types within the kidney and to their anatomical and functional polarity, investigation of these areas will be challenging indeed.

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Goals and Analytical Methodologies for Protein Disposition Studies

Ferraiolo¹,

Mohler²

1992

Pharmaceutical Biotechnology

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The binding and degradation of 125I-labelled insulin by rat kidney brush-border membranes

Cited by 8 publications

References 28 publications

Specific and Functional Insulin Receptors in Rat Renal Papilla

Specific and Functional Insulin Receptors in Rat Renal Papilla

The renal metabolism of insulin

Goals and Analytical Methodologies for Protein Disposition Studies

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