Increased plasma urotensin II levels in patients with diabetes mellitus

Abstract

A B S T R A C TUrotensin II (UII) is the most potent vasoconstrictor peptide, whereas it acts as a vasodilator on some arteries. We studied plasma levels of UII in diabetic patients with normal serum creatinine levels ( 90 µmol/l) and the expression of UII and its receptor in cultured human vascular endothelial cells. Plasma UII levels were significantly elevated by 1.8-fold in diabetic patients without proteinuria (7.8p0.6 fmol/ml ; P 0.0001) and 1.7-fold in those with overt proteinuria (7.3p0.9 fmol/ml ; P l 0.0018) when compared with healthy subjects (4.4p0.2 fmol/ml). No significant correlation was obtained between plasma UII levels and fasting blood sugar (P l 0.631 and P l 0.853 in non-proteinuric and proteinuric diabetic patients respectively), glycated haemoglobin levels (P l 0.376 and P l 0.888 respectively) or serum creatinine levels (P l 0.301 and P l 0.568 respectively). Reverse transcriptase-PCR analysis showed the expression of mRNAs encoding UII precursor and UII-receptor precursors in cultured human coronary artery endothelial cells and umbilical vein endothelial cells, suggesting that vascular endothelial cells are one of the sources of UII in blood. These findings suggest that elevation of plasma UII levels may be an important background factor in diabetic cardiovascular and organ complications in diabetic subjects without renal failure.

Role of urotensin II and its receptor in health and disease

“…A lack of correlation between U-II levels and fasting blood sugar levels demonstrated that hyperglycemia was not the cause of the U-II elevation [61]. See Table 2 for other plasma U-II data.…”

“…Renal disease, diabetes, and diabetic nephropathy There have been several studies from Totsune et al [61,70,71], who have shown that plasma U-II is elevated in renal failure and that this increase was greater in patients with a creatinine clearance of less than 30 ml·min −1 (compared with ≥70 ml·min −1 ) [71], and those on dialysis [70]. These increases in U-II may be attributed to decreased excretion of the peptide from the kidney, rather than increased expression.…”

Urotensin-II levels in acute coronary syndromes

“…Unlike several pAb from other commercial sources, our antibody interacts with truncated human U-II analogs such as [4][5][6][7][8][9][10][11] human U-II and [5][6][7][8][9][10][11] human U-II. These fragments show almost identical retention time on rp-HPLC columns and are equipotent agonists at the urotensin receptors compared with mature U-II.…”

“…Although the source of plasma U-II is still debated, its elevation in heart failure patients suggests participation in neurohormonal activation. Furthermore, plasma U-II is increased in diabetes [8], renal failure [9] and liver cirrhosis [10], advocating for a multisystemic involvement.…”

Urotensin-II is a nitric oxide-dependent vasodilator in the pial arteries of the newborn pig

“…The now renamed urotensin receptors can be found in various mammalian tissues such as vascular cells, cardiac muscle, and the brainstem and spinal cord motoneurons (Itoh et al, 1988;Ames et al, 1999;Maguire et al, 2000;Chartrel et al, 2004). Recent investigations revealed that UT-II may play a role in the pathogenesis of heart failure, hypertension, type II diabetes and renal dysfunction (Totsune et al, 2001;Douglas et al, 2002;Ng et al, 2002;Richards et al, 2002;Totsune et al, 2003;Cheung et al, 2004;Langham et al, 2004;Totsune et al, 2004). Elevated plasma UT-II concentrations, accompanied by an overexpression of the urotensin receptor, were observed in these pathologies (Ng et al, 2002;Richards et al, 2002;Russell et al, 2003;Totsune et al, 2003Totsune et al, , 2004Cheung et al, 2004;Langham et al, 2004).…”