کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8347513 | 1541679 | 2018 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Apelin-13 analogues show potent in vitro and in vivo insulinotropic and glucose lowering actions
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کلمات کلیدی
DIOpyroglutamylPGludiet induced obeseSGLT-2APJT2DMGIPGLP-1CCKKrebs Ringer bicarbonateKRbDPPDiabetes - بیماری قندInsulin secretion - ترشح انسولینType 2 diabetes mellitus - دیابت نوع دوWorld Health Organisation - سازمان بهداشت جهانیGlucose homeostasis - هوموستاز گلوکزglucagon-like peptide-1 - پپتید 1-گلوکاگون-مانندWHO - کهcholecystokinin - کولهسیستوکینینglucose-dependent insulinotropic polypeptide - گلیکول وابسته به پلی پپتید انسولینوتروپیکapelin receptor - گیرنده آپلین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Apelin-13 analogues show potent in vitro and in vivo insulinotropic and glucose lowering actions Apelin-13 analogues show potent in vitro and in vivo insulinotropic and glucose lowering actions](/preview/png/8347513.png)
چکیده انگلیسی
Nine structurally modified apelin-13 analogues were assessed for their in vitro and acute in vivo antidiabetic potential. Stability was assessed in mouse plasma and insulinotropic efficacy tested in cultured pancreatic BRIN-BD11 cells and isolated mouse pancreatic islets. Intracellular Ca2+ and cAMP production in BRIN-BD11 cells was determined, as was glucose uptake in 3T3-L1 adipocytes. Acute antihyperglycemic effects of apelin analogues were assessed following i.p. glucose tolerance tests (ipGGT, 18â¯mmol/kg) in normal and diet-induced-obese (DIO) mice and on food intake in normal mice. Apelin analogues all showed enhanced in vitro stability (up to 5.8-fold, t½â¯=â¯12.8â¯h) in mouse plasma compared to native apelin-13 (t½â¯=â¯2.1â¯h). Compared to glucose controls, stable analogues exhibited enhanced insulinotropic responses from BRIN-BD11 cells (up to 4.7-fold, pâ¯<â¯0.001) and isolated mouse islets (up to 5.3-fold) for 10â7â¯M apelin-13 amide (versus 7.6-fold for 10â7â¯M GLP-1). Activation of APJ receptors on BRIN-BD11 cells increased intracellular Ca2+ (up to 3.0-fold, pâ¯<â¯0.001) and cAMP (up to 1.7-fold, pâ¯<â¯0.01). Acute ipGTT showed improved insulinotropic and glucose disposal responses in normal and DIO mice (pâ¯<â¯0.05 and pâ¯<â¯0.01, respectively). Apelin-13 amide and (pGlu)apelin-13 amide were the most effective analogues exhibiting acute, dose-dependent and persistent biological actions. Both analogues stimulated insulin-independent glucose uptake by differentiated adipocytes (2.9-3.3-fold, pâ¯<â¯0.05) and inhibited food intake (26-33%, pâ¯<â¯0.001), up to 180â¯min in mice, versus saline. In contrast, (Ala13)apelin-13 and (Val13)apelin-13 inhibited insulin secretion, suppressed beta-cell signal transduction and stimulated food intake in mice. Thus, stable analogues of apelin-13 have potential for diabetes/obesity therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Peptides - Volume 100, February 2018, Pages 219-228
Journal: Peptides - Volume 100, February 2018, Pages 219-228
نویسندگان
F.P.M. O'Harte, V. Parthsarathy, C. Hogg, P.R. Flatt,