دورية أكاديمية
أعرض في EDS

Probing Insulin Sensitivity with Metabolically Competent Human Stem Cell-Derived White Adipose Tissue Microphysiological Systems.

التفاصيل البيبلوغرافية
العنوان: Probing Insulin Sensitivity with Metabolically Competent Human Stem Cell-Derived White Adipose Tissue Microphysiological Systems.
المؤلفون: Qi L; Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, CA, 94720, USA., Zushin PH; Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, CA, 94720, USA., Chang CF; Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, CA, 94720, USA., Lee YT; Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, CA, 94720, USA., Alba DL; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, 94143, USA.; Diabetes Center, University of California, San Francisco, San Francisco, CA, 94143, USA., Koliwad SK; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, 94143, USA.; Diabetes Center, University of California, San Francisco, San Francisco, CA, 94143, USA., Stahl A; Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, CA, 94720, USA.
المصدر: Small (Weinheim an der Bergstrasse, Germany) [Small] 2022 Jan; Vol. 18 (3), pp. e2103157. Date of Electronic Publication: 2021 Nov 10.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 101235338 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1613-6829 (Electronic) Linking ISSN: 16136810 NLM ISO Abbreviation: Small Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Weinheim, Germany : Wiley-VCH, c2005-
مواضيع طبية MeSH: Insulin Resistance*, Adipocytes ; Adipose Tissue ; Adipose Tissue, White ; Humans ; Insulin ; Stem Cells
مستخلص: Impaired white adipose tissue (WAT) function has been recognized as a critical early event in obesity-driven disorders, but high buoyancy, fragility, and heterogeneity of primary adipocytes have largely prevented their use in drug discovery efforts highlighting the need for human stem cell-based approaches. Here, human stem cells are utilized to derive metabolically functional 3D adipose tissue (iADIPO) in a microphysiological system (MPS). Surprisingly, previously reported WAT differentiation approaches create insulin resistant WAT ill-suited for type-2 diabetes mellitus drug discovery. Using three independent insulin sensitivity assays, i.e., glucose and fatty acid uptake and suppression of lipolysis, as the functional readouts new differentiation conditions yielding hormonally responsive iADIPO are derived. Through concomitant optimization of an iADIPO-MPS, it is abled to obtain WAT with more unilocular and significantly larger (≈40%) lipid droplets compared to iADIPO in 2D culture, increased insulin responsiveness of glucose uptake (≈2-3 fold), fatty acid uptake (≈3-6 fold), and ≈40% suppressing of stimulated lipolysis giving a dynamic range that is competent to current in vivo and ex vivo models, allowing to identify both insulin sensitizers and desensitizers.
(© 2021 Wiley-VCH GmbH.)
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معلومات مُعتمدة: UG3 DK120004 United States DK NIDDK NIH HHS; R01 DK118940 United States DK NIDDK NIH HHS; R01 DK126830 United States DK NIDDK NIH HHS; UH3 DK120004 United States DK NIDDK NIH HHS; P30 DK098722 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: human-induced pluripotent stem cells; insulin sensitivity; microphysiological system; organ-on-a-chip; white adipose tissue
المشرفين على المادة: 0 (Insulin)
تواريخ الأحداث: Date Created: 20211111 Date Completed: 20220307 Latest Revision: 20240923
رمز التحديث: 20240923
مُعرف محوري في PubMed: PMC8776615
DOI: 10.1002/smll.202103157
PMID: 34761526
قاعدة البيانات: MEDLINE
الوصف
تدمد:1613-6829
DOI:10.1002/smll.202103157