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Abstract

Insulin receptor (IR) gene expression at the mRNA level was investigated in hindlimb skeletal muscle, epididymal adipose tissue and in the liver of rats exposed to prolonged in vivo administration of deoxycorticosterone acetate (DOCA). Following treatment, plasma insulin levels were reduced while glucose levels increased compared to values in control rats. DOCA-treated animals showed an increase in blood pressure and a reduction in body weight. This treatment also induced hypokalemia and decreased plasma protein levels. Sodium levels were unaffected. Moreover, no differences in DNA and protein content or in the indicator of cell size (protein/DNA) were observed in the skeletal muscle or adipose tissue of animals. In contrast, there was a clear increase in the protein and DNA contents of the liver with no change in the indicator of cell size. Northern blot assays revealed 2 major IR mRNA species of approximately 9.5 and 7.5 Kb in the 3 tissues from control animals. DOCA treatment induced no change in the levels of either RNA species in skeletal muscle. However, a decrease of approximately 22% was detected in the levels of both species in adipose tissue whereas the liver showed an increase of 64%. These results provide the first evidence for an in vivo tissue-specific modulation of IR mRNA levels under experimental conditions of mineralocorticoid excess.

1,25-Dihydroxyvitamin D3 effects on the regulation of the insulin receptor gene in the hind limb muscle and heart of streptozotocin-induced diabetic rats

“…The presence of two INSR mRNA species of 9.5 and 7.5 Kb in the hind limb muscle of non-diabetic rats is consistent with earlier studies from our group [12,21] and others [35,36] showing species of comparable size in this same tissue. Regarding the presence of these two INSR mRNA species in the heart, to our knowledge this is the first description.…”

“…The relative amounts of these two INSR mRNA species measured as 9.5 Kb/7.5 Kb ratio were: 1.1  0.1 in hind limb muscle and 1.3  0.1 in the heart. These ratios are similar to those measured in adipose tissue [12,21] but lower than those detected in kidney [12]. Treatment with 1,25D 3 to non-diabetic rats did not affect any of the two INSR mRNA species in any of the tissues studied (Figure 1) and (Figure 2).…”

“…For Northern blot assays, RNA samples (30 µg) of hind limb muscle and heart, were denatured, electrophoresed in 1.1% agarose-formaldehyde gels and blotted onto nylon membranes as previously described [21]. Ethidium bromide staining of the 28 S and 18 S ribosomal RNAs was routinely checked before blotting as a control for sample loading, and after blotting as a control for RNA transfer.…”

Glucose Metabolism in Primary Aldosteronism

“…Additionally glucose-6-phosphatase (G6Pase), which is necessary for hepatic glucose release into the circulation showed an aldosterone dependent increase in its expression and the inhibitory effect of insulin on G6Pase gene expression was partially suppressed by aldosterone 37 38 . Furthermore, reduced IR expression could be documented in the liver of mineralocorticoid treated rats 15 61 . MR also seems to have an influence on hepatic synthesis of inflammatory cytokines as MRA admission in high fat, high fructose fed mice lead to a significant reduction in TNF-α, IL-6, and monocyte chemoattractant protein 1 levels in the liver 62 .…”

Angiotensinergic Signaling in the Brain Mediates Metabolic Effects of Deoxycorticosterone (DOCA)-Salt in C57 Mice

“…In addition to the blood pressure consequences of DOCA-salt, several studies have noted negative body weight effects of this treatment (4–5, 16–17). These effects appear to be dependent upon the phase of DOCA-salt treatment, however, as the body weight effects do not appear until after the onset of hypertension and the suppression of renal renin expression, and are confounded by water and sodium loading during the early phases of treatment (5).…”