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• W3168140741 startingPage "2215" @default.
• W3168140741 abstract "To assess the beneficial metabolic effects of the nonapeptide hormone, arginine vasopressin (AVP), on metabolism.We exchanged amino acids at position 3 and 8 of AVP, namely phenylalanine and arginine, with those of oxytocin, to generate novel analogues with altered receptor selectivity. Secondary modification by N-terminal acetylation was used to impart stability to circulating endopeptidases. Analogues were screened for degradation, bioactivity in rodent/human clonal beta cells and primary murine islets, together with evaluation of receptor activation profile.Analogue Ac3IV, which lacked effects at the V2 receptors responsible for modulation of fluid balance, was selected as the lead compound for assessment of antidiabetic efficacy in high-fat-fed mice. Twice-daily administration of Ac3IV, or the gold standard control exendin-4, for 22 days, reduced energy intake as well as body weight and fat content. Both interventions decreased circulating glucose levels, enhanced insulin sensitivity, and substantially improved glucose tolerance and related insulin secretion in response to an intraperitoneal or oral glucose challenge. The peptides decreased total- and increased HDL-cholesterol, but only Ac3IV decreased LDL-cholesterol, triglyceride and non-fasting glucagon concentrations. Elevations of islet and beta-cell areas were partially reversed, accompanied by suppressed islet cell proliferation, decreased beta-cell apoptosis and, in the case of exendin-4, also decreased alpha-cell apoptosis.AVP-based therapies that exclusively target V1a and V1b receptors may have significant therapeutic potential for the treatment of obesity and related diabetes, and merit further clinical exploration." @default.
• W3168140741 created "2021-06-22" @default.
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• W3168140741 date "2021-06-27" @default.
• W3168140741 modified "2023-10-16" @default.
• W3168140741 title "Weight‐reducing, lipid‐lowering and antidiabetic activities of a novel arginine vasopressin analogue acting at the V1a and V1b receptors in high‐fat‐fed mice" @default.
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• W3168140741 doi "https://doi.org/10.1111/dom.14462" @default.
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• W3168140741 hasPublicationYear "2021" @default.
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