کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5823900 | 1118373 | 2012 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Degradation, insulin secretion, glucose-lowering and GIP additive actions of a palmitate-derivatised analogue of xenin-25
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کلمات کلیدی
ESIMALDI-TOFGLP-1GIPFASTALysine - لیزینLYS - لیستglucagon-like peptide-1 - پپتید 1-گلوکاگون-مانندhigh performance liquid chromatography - کروماتوگرافی مایع با کارایی بالاHPLC - کروماتوگرافی مایعی کاراglucose-dependent insulinotropic polypeptide - گلیکول وابسته به پلی پپتید انسولینوتروپیکelectrospray ionisation - یونیزاسیون الکترو اسپری
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Degradation, insulin secretion, glucose-lowering and GIP additive actions of a palmitate-derivatised analogue of xenin-25 Degradation, insulin secretion, glucose-lowering and GIP additive actions of a palmitate-derivatised analogue of xenin-25](/preview/png/5823900.png)
چکیده انگلیسی
Xenin-25, a K-cell derived peptide co-secreted with glucose-dependent insulinotropic polypeptide (GIP), has recently been shown to have glucose homeostatic actions and potentiate the insulinotropic effect of GIP. However, the biological actions of xenin-25 are brief due to rapid metabolism, yet little is known regarding enzymatic degradation of this peptide. Therefore, the present study has fully characterised the plasma enzymatic degradation products of xenin-25. We have also generated a novel acylated xenin-25 analogue, xenin-25(Lys13PAL), and evaluated its stability, biological action profile and therapeutic applicability compared to the native peptide. In contrast to xenin-25, xenin-25(Lys13PAL) was completely resistant to plasma enzyme degradation. Insulinotropic responses of xenin-25(Lys13PAL) in clonal beta-cells were similar to native xenin-25, moreover xenin-25(Lys13PAL) significantly (p < 0.05 to p < 0.001) potentiated the insulin releasing action of (D-Ala2)GIP. When administered together with glucose to normal mice, the glycaemic excursion was significantly (p < 0.05) less and overall insulin secretory effect significantly (p < 0.05) greater for xenin-25(Lys13PAL) when compared to xenin-25 mice. Glucose-lowering and insulin releasing effects of both peptides was less prominent in high fat fed mice and ob/ob mice. However, xenin-25 significantly (p < 0.05) augmented the glucose-lowering action of (D-Ala2)GIP in both groups of mice. Similarly, xenin-25(Lys13PAL) potentiated (p < 0.05) the gluco-regulatory effect of (D-Ala2)GIP. Overall, these data indicate that palmitate-derivatised analogues of xenin-25 represent a novel class of GIP potentiator drugs for possible type 2 diabetes therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 84, Issue 3, 1 August 2012, Pages 312-319
Journal: Biochemical Pharmacology - Volume 84, Issue 3, 1 August 2012, Pages 312-319
نویسندگان
Christine M.A. Martin, Victor A. Gault, Stephen McClean, Peter R. Flatt, Nigel Irwin,