Amylin stimulates proximal tubular sodium transport and cell proliferation in the rat kidney

Abstract

In autoradiographic studies in anesthetized rats, 125I-labeled amylin binding was associated with proximal convoluted tubules but not distal tubules, interstitium, or glomeruli in the renal cortex. Split-drop micropuncture experiments showed that perfusion of the peritubular capillaries with amylin (10(-9) M) stimulated proximal tubular fluid absorption by 28%. This effect was inhibited by luminal addition of ethylisopropylamiloride, indicating mediation by a brush-border Na+/H+ exchanger. Intravenous infusion of an amylin binding antagonist, AC-187, reduced proximal fluid reabsorption (22%) in anesthetized rats, indicating a role for endogenous amylin in salt homeostasis. In primary cultures of rat proximal tubule cells, amylin (10(-7) M) stimulated proliferation with a potency equal to epidermal growth factor. Peptide antagonists (AC-187, AC-413, and AC-512) of the amylin binding sites in the renal cortex blocked the mitogenic action of amylin. We conclude that amylin acts on renal proximal tubules to promote sodium and water reabsorption and cell proliferation. These novel actions may have implications for the development of hypertension for example in non-insulin-dependent diabetes mellitus and obesity in which hyperamylinemia has been observed.

Amylin: Pharmacology, Physiology, and Clinical Potential

“…Thus, amylin and its receptor(s) may contribute to the development or maintenance of hypertension . Amylin may also act as a growth factor in the kidney and may control water and sodium reabsorption (Harris et al, 1997;. In anesthetized rats, amylin infusion can also promote diuresis and natriuresis (Vine et al, 1998b).…”

Localization of Calcitonin Receptor mRNA in Rat Kidney: an In Situ Hybridization Study

“…In addition, CTR functions as a receptor of amylin by co-expression with reported receptor activity modifying protein (RAMP) 1 and RAMP3 in human CTR transfected cells [3,25]. Because amylin stimulated sodium and water re-absorption on primary cultured proximal tubular cells [11], CTR in the proximal tubule may have some function as an amylin receptor.…”

Unaltered pancreatic islet blood perfusion in islet amyloid polypeptide-deficient mice

“…19,33). IAPP has been reported to have mitogenic actions, for example on tubular epithelial cells in the kidney (38). To exclude differences in islet mass between the IAPP (2/2) mice and the IAPP (+/+) control mice, possibly caused by such IAPP-mediated mitogenic effects, we determined the islet mass in each animal and also expressed islet blood flow per islet weight; in this case also no differences were found, which is in agreement with our previous finding using image analysis to determine beta-cell mass (32).…”