Aldosterone suppresses expression of an avian colonic sodium-glucose cotransporter

Abstract

Transport in the colon of the domestic fowl switches from sodium-linked hexose and amino acid cotransport on high-salt intake to amiloride-sensitive sodium channel expression on low-salt (LS) diets. The present experiments were designed to investigate the role of aldosterone in suppression of the colonic sodium-glucose luminal cotransporter (SGLT). LS-adapted hens were resalinated with or without simultaneous aldosterone treatment. Changes in the electrophysiological responses and SGLT protein expression levels were examined at 1, 3, and 7 days of treatment. Serum aldosterone levels fell from approximately 400 pmol/l in LS-adapted hens to values below the detection limit (<44 pmol/l) after 1 day of resalination. At the same time, glucose-stimulated short circuit current (I(SC)) increased from 20.9 +/- 8.7 to 56.3 +/- 15.5 microA/cm(2), whereas amiloride-sensitive I(SC) decreased from -68.9 +/- 12.7 microA/cm(2) on LS to +0.6 +/- 12.0 microA/cm(2). Glucose-stimulated I(SC) increased further at 3 and 7 days of resalination, whereas amiloride-sensitive I(SC) remained suppressed. When resalinated birds were simultaneously treated with aldosterone, the LS pattern of high amiloride-sensitive I(SC) and low glucose-stimulated I(SC) was maintained. Immunoblotting results from the same tissues demonstrated that SGLT-like protein expression increased following resalination. Aldosterone treatment completely blocked this effect. These results demonstrate that aldosterone suppresses both activity and protein expression of hen colonic SGLT. Resalination either through decreased aldosterone or other factors may be able to activate SGLT activity independently of increases in protein expression.

Regulation of SGLT1 expression in response to Na+ intake

“…Although there is a lower concentration of this ion all through the gut of LS diet birds (data not shown), only in the ileum and rectum were there evident decreases of SGLT1 expression, whereas the jejunum remained unaffected. These results suggest that the signal that controls SGLT1 expression might be not luminal but secondary to diet-induced changes in circulating aldosterone (20). Supporting this view, a recent study demonstrated that aldosterone itself was able to mimic the effects of a low-Na ϩ diet (14,20) with no changes in the luminal Na ϩ content.…”

“…These results suggest that the signal that controls SGLT1 expression might be not luminal but secondary to diet-induced changes in circulating aldosterone (20). Supporting this view, a recent study demonstrated that aldosterone itself was able to mimic the effects of a low-Na ϩ diet (14,20) with no changes in the luminal Na ϩ content. SGLT1 mRNA was detected in all three intestinal segments of the chicken without regional differences, and it showed a single transcript of 3.8 kb, as found by Gal-Garber et al (11).…”

“…It has been shown that a low-Na ϩ diet induces a dramatic reduction in hexose transport in the rectum and the ileum (12) that is rapidly reversed by resalination (13). Because low-Na ϩ intake induces secondary hyperaldosteronism, most of the effects observed are believed to be regulated by aldosterone (14,20,26).…”

Role of aldosterone and angiotensin II in insulin resistance: an update

“…In rodents increased aldosterone production mediated by insulin in a dose-dependent manner in glomerulosa zone cells has been reported. 13 Another study 14 demonstrated that aldosterone suppresses the expression of glucose transporters in avian animal colonic cells, whereas in human promonocytes aldosterone promotes down-regulation of the insulin receptor as well as reduced subcutaneous adipose tissue insulin receptor expression by approximately 54%. 15 Clinical studies have confirmed insulin resistance, evaluated through Homeostatic Model Assessment (HOMA), as well as impaired insulin-stimulated glucose utilization (measured by euglycaemic hyperinsulinaemic clamp) in PA patients but not in essential hypertensive individuals.…”

New ideas about aldosterone signaling in epithelia

“…Glucocorticoids via GR repress expression of a host of genes. Recent studies also have identified several aldosterone-repressed genes and proteins (92,135,154). Compared with induction, less is known about the molecular mechanisms of direct gene repression in response to corticosteroids.…”