دورية أكاديمية
أعرض في EDS

The Inhibitory G Protein α-Subunit, Gαz, Promotes Type 1 Diabetes-Like Pathophysiology in NOD Mice.

التفاصيل البيبلوغرافية
العنوان: The Inhibitory G Protein α-Subunit, Gαz, Promotes Type 1 Diabetes-Like Pathophysiology in NOD Mice.
المؤلفون: Fenske RJ; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705.; Research Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705., Cadena MT; Research Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Wisconsin-Madison, Madison, Wisconsin 53705., Harenda QE; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53705., Wienkes HN; Research Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Wisconsin-Madison, Madison, Wisconsin 53705., Carbajal K; Research Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Wisconsin-Madison, Madison, Wisconsin 53705., Schaid MD; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705.; Research Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705., Laundre E; Research Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Wisconsin-Madison, Madison, Wisconsin 53705., Brill AL; Research Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Wisconsin-Madison, Madison, Wisconsin 53705., Truchan NA; Research Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Wisconsin-Madison, Madison, Wisconsin 53705., Brar H; Research Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Wisconsin-Madison, Madison, Wisconsin 53705., Wisinski J; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705.; Research Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Wisconsin-Madison, Madison, Wisconsin 53705., Cai J; Molecular Medicine Program, Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Nutrition, and Department of Biological Chemistry, University of Utah School of Medicine, Salt Lake City, Utah 84112.; George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah 84112., Graham TE; Molecular Medicine Program, Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Nutrition, and Department of Biological Chemistry, University of Utah School of Medicine, Salt Lake City, Utah 84112.; George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah 84112., Engin F; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Wisconsin-Madison, Madison, Wisconsin 53705.; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53705., Kimple ME; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705.; Research Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Wisconsin-Madison, Madison, Wisconsin 53705.; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, Wisconsin 53705.
المصدر: Endocrinology [Endocrinology] 2017 Jun 01; Vol. 158 (6), pp. 1645-1658.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375040 Publication Model: Print Cited Medium: Internet ISSN: 1945-7170 (Electronic) Linking ISSN: 00137227 NLM ISO Abbreviation: Endocrinology Subsets: MEDLINE
أسماء مطبوعة: Publication: 2017- : New York : Oxford University Press
Original Publication: Los Angeles, Calif. : Association for the Study of Internal Secretions,
مواضيع طبية MeSH: Diabetes Mellitus, Experimental/*genetics , Diabetes Mellitus, Type 1/*genetics , GTP-Binding Protein alpha Subunits/*genetics, Animals ; Apoptosis/genetics ; Blood Glucose/metabolism ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology ; Diabetes Mellitus, Type 1/metabolism ; Diabetes Mellitus, Type 1/pathology ; Female ; Insulin-Secreting Cells/metabolism ; Insulin-Secreting Cells/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Mice, Transgenic ; Streptozocin
مستخلص: The α-subunit of the heterotrimeric Gz protein, Gαz, promotes β-cell death and inhibits β-cell replication when pancreatic islets are challenged by stressors. Thus, we hypothesized that loss of Gαz protein would preserve functional β-cell mass in the nonobese diabetic (NOD) model, protecting from overt diabetes. We saw that protection from diabetes was robust and durable up to 35 weeks of age in Gαz knockout mice. By 17 weeks of age, Gαz-null NOD mice had significantly higher diabetes-free survival than wild-type littermates. Islets from these mice had reduced markers of proinflammatory immune cell infiltration on both the histological and transcript levels and secreted more insulin in response to glucose. Further analyses of pancreas sections revealed significantly fewer terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)-positive β-cells in Gαz-null islets despite similar immune infiltration in control mice. Islets from Gαz-null mice also exhibited a higher percentage of Ki-67-positive β-cells, a measure of proliferation, even in the presence of immune infiltration. Finally, β-cell-specific Gαz-null mice phenocopy whole-body Gαz-null mice in their protection from developing hyperglycemia after streptozotocin administration, supporting a β-cell-centric role for Gαz in diabetes pathophysiology. We propose that Gαz plays a key role in β-cell signaling that becomes dysfunctional in the type 1 diabetes setting, accelerating the death of β-cells, which promotes further accumulation of immune cells in the pancreatic islets, and inhibiting a restorative proliferative response.
(Copyright © 2017 Endocrine Society.)
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معلومات مُعتمدة: P30 CA014520 United States CA NCI NIH HHS; R01 DK102598 United States DK NIDDK NIH HHS; T32 DK007665 United States DK NIDDK NIH HHS; F31 DK109698 United States DK NIDDK NIH HHS; K01 DK102488 United States DK NIDDK NIH HHS
المشرفين على المادة: 0 (Blood Glucose)
0 (GTP-Binding Protein alpha Subunits)
0 (Gnaz protein, mouse)
5W494URQ81 (Streptozocin)
تواريخ الأحداث: Date Created: 20170419 Date Completed: 20170907 Latest Revision: 20210218
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC5460933
DOI: 10.1210/en.2016-1700
PMID: 28419211
قاعدة البيانات: MEDLINE
الوصف
تدمد:1945-7170
DOI:10.1210/en.2016-1700