دورية أكاديمية
Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis.
| العنوان: | Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis. |
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| المؤلفون: | Jiang Z; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA., Zhao M; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA., Voilquin L; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA., Jung Y; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA., Aikio MA; Department of Cell Biology, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA., Sahai T; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA., Dou FY; Department of Cell Biology, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA., Roche AM; Department of Cell Biology, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA., Carcamo-Orive I; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA., Knowles JW; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Prevention Research Center, Stanford University, Stanford, CA 94305, USA., Wabitsch M; Division of Pediatric Endocrinology and Diabetes, University Medical Center Ulm, Ulm, Germany., Appel EA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Materials Science & Engineering, Stanford University, Stanford, CA 94305, USA; Department of Pediatrics (Endocrinology), Stanford University, Stanford, CA 94305, USA., Maikawa CL; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA., Camporez JP; Department of Physiology, Ribeirao Preto School of Medicine, University of Sao Paulo, Sao Paulo, Brazil; Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06519, USA., Shulman GI; Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06519, USA; Department of Cellular and Molecular Physiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06519, USA., Tsai L; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Rosen ED; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Gardner CD; Stanford University, Stanford, CA 94305, USA., Spiegelman BM; Department of Cell Biology, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA., Svensson KJ; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: katrinjs@stanford.edu. |
| المصدر: | Cell metabolism [Cell Metab] 2021 Sep 07; Vol. 33 (9), pp. 1836-1852.e11. Date of Electronic Publication: 2021 Aug 03. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101233170 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-7420 (Electronic) Linking ISSN: 15504131 NLM ISO Abbreviation: Cell Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2005- |
| مواضيع طبية MeSH: | Diabetes Mellitus, Type 2*/drug therapy , Diabetes Mellitus, Type 2*/metabolism , Fatty Liver*/drug therapy , Fatty Liver*/metabolism , Insulin Resistance*, Adipokines ; Animals ; Diet, High-Fat ; Glucose/metabolism ; Intercellular Signaling Peptides and Proteins ; Lipid Metabolism/physiology ; Lipogenesis ; Liver/metabolism ; Mice ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases/metabolism |
| مستخلص: | With the increasing prevalence of type 2 diabetes and fatty liver disease, there is still an unmet need to better treat hyperglycemia and hyperlipidemia. Here, we identify isthmin-1 (Ism1) as an adipokine and one that has a dual role in increasing adipose glucose uptake while suppressing hepatic lipid synthesis. Ism1 ablation results in impaired glucose tolerance, reduced adipose glucose uptake, and reduced insulin sensitivity, demonstrating an endogenous function for Ism1 in glucose regulation. Mechanistically, Ism1 activates a PI3K-AKT signaling pathway independently of the insulin and insulin-like growth factor receptors. Notably, while the glucoregulatory function is shared with insulin, Ism1 counteracts lipid accumulation in the liver by switching hepatocytes from a lipogenic to a protein synthesis state. Furthermore, therapeutic dosing of recombinant Ism1 improves diabetes in diet-induced obese mice and ameliorates hepatic steatosis in a diet-induced fatty liver mouse model. These findings uncover an unexpected, bioactive protein hormone that might have simultaneous therapeutic potential for diabetes and fatty liver disease. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Nat Rev Endocrinol. 2021 Dec;17(12):709-710. (PMID: 34580477) |
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| معلومات مُعتمدة: | R01 DK120565 United States DK NIDDK NIH HHS; P30 DK045735 United States DK NIDDK NIH HHS; K99 DK111916 United States DK NIDDK NIH HHS; R01 DK116750 United States DK NIDDK NIH HHS; R01 DK031405 United States DK NIDDK NIH HHS; P30 CA124435 United States CA NCI NIH HHS; R01 DK119254 United States DK NIDDK NIH HHS; R01 DK087092 United States DK NIDDK NIH HHS; R00 DK111916 United States DK NIDDK NIH HHS; UL1 TR001863 United States TR NCATS NIH HHS; R01 DK061562 United States DK NIDDK NIH HHS; R01 DK125260 United States DK NIDDK NIH HHS; R01 DK102173 United States DK NIDDK NIH HHS; P30 DK046200 United States DK NIDDK NIH HHS; R37 DK031405 United States DK NIDDK NIH HHS; P30 DK057521 United States DK NIDDK NIH HHS; P30 DK034989 United States DK NIDDK NIH HHS; P30 DK116074 United States DK NIDDK NIH HHS |
| فهرسة مساهمة: | Keywords: adipokine; cellular signaling; diabetes; glucose uptake; hepatic steatosis; lipogenesis |
| المشرفين على المادة: | 0 (Adipokines) 0 (Intercellular Signaling Peptides and Proteins) 0 (isthmin protein, mouse) IY9XDZ35W2 (Glucose) |
| تواريخ الأحداث: | Date Created: 20210804 Date Completed: 20220407 Latest Revision: 20220910 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8429235 |
| DOI: | 10.1016/j.cmet.2021.07.010 |
| PMID: | 34348115 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1932-7420 |
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| DOI: | 10.1016/j.cmet.2021.07.010 |