The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats.
نویسندگان
چکیده
Urotensin-II (U-II) is a cyclic peptide that acts through a specific G-protein-coupled receptor, UT receptor. Urotensin-II and UT receptors have been described in pancreas and kidney, but their function is not well understood. We studied the effects of chronic treatment of diabetic rats with the orally active selective U-II receptor antagonist palosuran. Streptozotocin treatment causes pancreatic beta-cell destruction and leads to the development of hyperglycemia, dyslipidemia, and renal dysfunction. Long-term treatment of streptozotocin-induced diabetic rats with palosuran improved survival, increased insulin, and slowed the increase in glycemia, glycosylated hemoglobin, and serum lipids. Furthermore, palosuran increased renal blood flow and delayed the development of proteinuria and renal damage. The U-II system is unique in that it plays a role both in insulin secretion and in the renal complications of diabetes. Urotensin receptor antagonism might be a new therapeutic approach for the treatment of diabetes.
منابع مشابه
Effect of the urotensin receptor antagonist palosuran in hypertensive patients with type 2 diabetic nephropathy.
The urotensin system has been hypothesized to play an important role in the pathophysiology of diabetic nephropathy. In this multicenter, randomized, double-blind, placebo-controlled, 2-period crossover study, the effects of the urotensin receptor antagonist palosuran on urinary albumin excretion and blood pressure in hypertensive patients with type 2 diabetic nephropathy treated with a single ...
متن کاملPharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin System.
Urotensin-II (U-II) is a cyclic peptide now described as the most potent vasoconstrictor known. U-II binds to a specific G protein-coupled receptor, formerly the orphan receptor GPR14, now renamed urotensin receptor (UT receptor), and present in mammalian species. Palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt) is a new potent...
متن کاملThe effects of Mas receptor antagonist (A779) and renal perfusion pressure on serum nitrite concentration in male and female rats when angiotensin II receptors 1 & 2 were blocked
Introduction: Renin angiotensin system has an important role in blood pressure and renal functions. Active angiotensin-converting enzyme 2 converts angiotensin I into angiotensin-(1-7) which is a vasodilator hormone and interacts with nitric oxide changes as well as other angiotensin II receptors. In this study we evaluated the role of Mas receptor antagonist (A779) and renal perfusion press...
متن کاملPotential Clinical Implications of the Urotensin II Receptor Antagonists
Urotensin II (UII) binds to its receptor, UT, playing an important role in the heart, kidneys, pancreas, adrenal gland, and central nervous system. In the vasculature, it acts as a potent endothelium-independent vasoconstrictor and endothelium-dependent vasodilator. In disease states, however, this constriction-dilation equilibrium is disrupted. There is an upregulation of the UII system in hea...
متن کاملUrotensin-II and its receptor (UT-R) are expressed in rat brain endothelial cells, and urotensin-II via UT-R stimulates angiogenesis in vivo and in vitro.
Urotensin-II (UII), along its receptor UT-R, is widely expressed in the cardiovascular system, where it exerts regulatory actions under both physiological and pathological conditions. Real-time PCR and immunocytochemistry demonstrated the expression of UII and UT-R as mRNA and protein in rat neuromicrovascular endothelial cells (NECs). UII did not affect the proliferation rate of cultured NECs,...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of pharmacology and experimental therapeutics
دوره 316 3 شماره
صفحات -
تاریخ انتشار 2006