Interaction of insulin with the renal proximal tubular cell

Insulin is known to regulate both metabolic and transport functions in the renal proximal tubule. Insulin present in plasma and in glomerular ultrafiltrate is known to be degraded at this nephron site. This paper summarizes what is known about these processes and about the mechanisms by which the actions of insulin and the degradation of insulin are effected in the proximal tubular epithelial cell. Recent studies have characterized the binding of insulin to specific receptors present in the proximal tubular basolateral membrane. Binding of insulin to its receptor in this membrane is thought to initiate events that lead to the phosphorylation of that receptor. Such insulin-stimulated phosphorylation may mediate hormonal action. A possible role for insulin-like growth factor II in the modulation of the actions of insulin has been suggested by observations in the kidney and in nonrenal cells. These findings are integrated into a model characterizing the nature of the interaction of insulin with the renal proximal tubular cell.

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Phosphate transport across renal proximal tubular cell membranes

AJP Renal Physiology ◽

10.1152/ajprenal.1986.251.3.f385 ◽

1986 ◽

Vol 251 (3) ◽

pp. F385-F398 ◽

Cited By ~ 3

Author(s):

M. R. Hammerman

Keyword(s):

Brush Border ◽

Phosphate Transport ◽

Tubular Epithelial Cell ◽

Proximal Tubular Cell ◽

Tubular Cell ◽

Basolateral Membranes ◽

Renal Proximal Tubular Cell ◽

Proximal Tubular ◽

Renal Proximal Tubular ◽

Editorial Review

The transport of phosphate across the plasma membrane of the renal proximal tubular epithelial cell is thought to take place through the activities of specific transporters located in the membrane. The activities of these transporters are essential to effect the reabsorption of phosphate present in glomerular ultrafiltrate. In addition, their activities are thought to be important for the maintenance of metabolic functions in the proximal tubular cell. Studies utilizing proximal tubular brush-border and basolateral membranes isolated from mammalian kidney have provided significant insights into the mechanisms by which phosphate transport across the brush-border and basolateral membranes of the intact proximal tubular cell occurs and is modulated. In this editorial review, the results of many of these studies are summarized. Particular emphasis is placed on studies that utilized isolated membranes to determine the mechanism by which the phosphaturic action of parathyroid hormone is mediated in the renal proximal tubule. On the basis of studies conducted in isolated membranes and in more physiologically intact preparations, models are constructed to integrate the role of the brush-border and basolateral membranes in the transport of phosphate into and out of the renal proximal tubular cell.

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Calcium-activated phospholipase C associated with canine renal basolateral membranes

AJP Renal Physiology ◽

10.1152/ajprenal.1987.252.1.f74 ◽

1987 ◽

Vol 252 (1) ◽

pp. F74-F82

Author(s):

S. A. Rogers ◽

M. R. Hammerman

Keyword(s):

Phospholipase C ◽

Basolateral Membrane ◽

Proximal Tubular Cell ◽

Tubular Cell ◽

Free Calcium ◽

Basolateral Membranes ◽

Renal Proximal Tubular Cell ◽

Dog Kidney ◽

Proximal Tubular ◽

Renal Proximal Tubular

To determine whether calcium-activated phospholipase C effects breakdown of phospholipids present in the basolateral membrane of the renal proximal tubular cell we incubated proximal tubular basolateral membranes isolated from dog kidney in the absence and presence of deoxycholate, and varied free calcium from 0 to 300 microM. Following incubations, lipids were extracted from membranes and separated using thin-layer chromatography. In the absence of deoxycholate, neither phosphatidylinositol nor diglyceride extractable from basolateral membranes changed significantly as calcium was increased. In the presence of deoxycholate, extractable phosphatidylinositol and diglyceride did not change significantly as free calcium was elevated from 0 to 0.03 microM, but phosphatidylinositol decreased and diglyceride increased progressively as 0.03-300 microM free calcium was included in incubations. Most of the increased extractable diglyceride could be accounted for by hydrolysis of phosphatidylinositol as reflected by decreased extractable phosphatidylinositol. Our findings suggest that calcium-activated phospholipase C effects breakdown of phospholipids present in the basolateral portion of the plasma membrane of the renal proximal tubular cell. It is possible that this enzyme plays a role in stimulating protein kinase c at this site.

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Binding of IGF I and IGF I-stimulated phosphorylation in canine renal basolateral membranes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.251.1.e32 ◽

1986 ◽

Vol 251 (1) ◽

pp. E32-E41 ◽

Cited By ~ 2

Author(s):

M. R. Hammerman ◽

J. R. Gavin

Keyword(s):

Insulin Receptor ◽

Basolateral Membrane ◽

Proximal Tubular Cell ◽

Membrane Receptors ◽

Tubular Cell ◽

Basolateral Membranes ◽

Renal Proximal Tubular Cell ◽

Igf I ◽

Proximal Tubular ◽

Renal Proximal Tubular

To characterize the interaction of the renal proximal tubular cell with insulin like growth factor I (IGF I), we measured binding of 125I-IGF I to proximal tubular basolateral membranes from dog kidney and induced IGF I-stimulated phosphorylation of basolateral membranes. Specific binding of 125I-IGF I to basolateral membranes was observed that was half-maximal at between 10(-9) and 10(-8) M IGF I. 125I-IGF I was affinity cross-linked to a 135,000 Mr protein in basolateral membranes that was distinct from the alpha-subunit of the insulin receptor and from the IGF II receptor. IGF I-stimulated phosphorylation of a 92,000 Mr protein was effected in detergent-solubilized membranes incubated with 100 microM [gamma-32P]ATP. The 32P-labeled protein was distinct from the beta-subunit of the insulin receptor, the 32P phosphorylation of which was stimulated by insulin. We conclude that specific receptors for IGF I are present in the basolateral membrane of the renal proximal tubular cell. Physiological actions of IGF I at this nephron site may occur through the binding of this peptide circulating in plasma, to specific basolateral membrane receptors, followed by IGF I stimulated phosphorylation.

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Glutamine transport in basolateral vesicles from dogs with acute respiratory acidosis

AJP Renal Physiology ◽

10.1152/ajprenal.1984.247.3.f403 ◽

1984 ◽

Vol 247 (3) ◽

pp. F403-F407 ◽

Cited By ~ 1

Author(s):

D. W. Windus ◽

S. Klahr ◽

M. R. Hammerman

Keyword(s):

Basolateral Membrane ◽

Respiratory Acidosis ◽

Membrane Vesicles ◽

Proximal Tubular Cell ◽

Tubular Cell ◽

Basolateral Membrane Vesicles ◽

Renal Proximal Tubular Cell ◽

Glutamine Transport ◽

Proximal Tubular ◽

Renal Proximal Tubular

It has been shown that acute respiratory acidosis in dogs results in enhanced renal extraction of L-glutamine from plasma and increased ammonia excretion per nephron. To determine whether a component of the enhanced L-glutamine extraction results from increased transport of L-glutamine across the basolateral membrane into the renal proximal tubular cell, we measured Na+ gradient-dependent L-[3H]glutamine transport in proximal tubular basolateral membrane vesicles isolated from kidneys of normal dogs and from kidneys of dogs following 2 h of acute respiratory acidosis. The initial rate of Na+ gradient-dependent L-[3H] glutamine uptake (15 s) was increased significantly in basolateral membrane vesicles from the acidotic compared with normal dogs. Increased uptake could be measured under conditions in which changes in membrane potential resulting from fluxes of solute were minimized. We conclude that an adaptation occurs in the basolateral membrane of the renal proximal tubular cell during acute respiratory acidosis that allows increased transport of L-glutamine across the membrane into the proximal tubular cell. This adaptation may permit increased ammonia production per nephron.

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