| Adiponectin lowers glucose production by increasing SOGA. | |
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MedLine Citation:
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PMID: 20813965 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Adiponectin is a hormone that lowers glucose production by increasing liver insulin sensitivity. Insulin blocks the generation of biochemical intermediates for glucose production by inhibiting autophagy. However, autophagy is stimulated by an essential mediator of adiponectin action, AMPK. This deadlock led to our hypothesis that adiponectin inhibits autophagy through a novel mediator. Mass spectrometry revealed a novel protein that we call suppressor of glucose by autophagy (SOGA) in adiponectin-treated hepatoma cells. Adiponectin increased SOGA in hepatocytes, and siRNA knockdown of SOGA blocked adiponectin inhibition of glucose production. Furthermore, knockdown of SOGA increased late autophagosome and lysosome staining and the secretion of valine, an amino acid that cannot be synthesized or metabolized by liver cells, suggesting that SOGA inhibits autophagy. SOGA decreased in response to AICAR, an activator of AMPK, and LY294002, an inhibitor of the insulin signaling intermediate, PI3K. AICAR reduction of SOGA was blocked by adiponectin; however, adiponectin did not increase SOGA during PI3K inhibition, suggesting that adiponectin increases SOGA through the insulin signaling pathway. SOGA contains an internal signal peptide that enables the secretion of a circulating fragment of SOGA, providing a surrogate marker for intracellular SOGA levels. Circulating SOGA increased in parallel with adiponectin and insulin activity in both humans and mice. These results suggest that adiponectin-mediated increases in SOGA contribute to the inhibition of glucose production. |
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Authors:
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Rachael B Cowherd; Rachael B Cowerd; Melissa M Asmar; J McKee Alderman; Elizabeth A Alderman; Alaina L Garland; Walker H Busby; Wanda M Bodnar; Ivan Rusyn; Benjamin D Medoff; Roland Tisch; Elizabeth Mayer-Davis; James A Swenberg; Steven H Zeisel; Terry P Combs |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-02 |
Journal Detail:
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Title: The American journal of pathology Volume: 177 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-01 Completed Date: 2011-03-11 Revised Date: 2012-04-27 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 1936-45 Citation Subset: AIM; IM |
Affiliation:
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Departments of Nutrition, School of Medicine and Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/FJ977045 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases
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metabolism Adiponectin / blood*, pharmacology* Adult Amino Acid Sequence Animals Autophagy Blood Glucose / metabolism* Cloning, Molecular Female Humans Hypoglycemic Agents / blood* Insulin / blood* Liver / cytology, metabolism* Mice Mice, Inbred C57BL Mice, Inbred NOD Mice, Obese Mice, Transgenic Middle Aged Molecular Sequence Data Peptide Fragments / immunology Proteins / genetics, immunology, metabolism* Rabbits Signal Transduction Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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AI066075/AI/NIAID NIH HHS; DK056350/DK/NIDDK NIH HHS; DK075573/DK/NIDDK NIH HHS; ES010126/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adiponectin; 0/Blood Glucose; 0/Hypoglycemic Agents; 0/Insulin; 0/Peptide Fragments; 0/Proteins; 0/suppressor of glucose by autophagy protein, mouse; EC 2.7.11.1/AMP-Activated Protein Kinases |
| Comments/Corrections | |
Comment In:
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Am J Pathol. 2010 Oct;177(4):1600-2
[PMID:
20813966
]
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Erratum In:
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Am J Pathol. 2011 Mar;178(3):1406 Note: Cowerd, Rachael B [corrected to Cowherd, Rachael B] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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