| Neutrophil Proteinase 3 Induces Diabetes in a Mouse Model of Glucose Tolerance. | |
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MedLine Citation:
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PMID: 22014109 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Type 1 diabetes is considered to be an autoimmune disease in which T cells attack pancreatic islet cells. Impaired glucose tolerance with type 2 diabetes has been classified as an obesity-associated metabolic syndrome. However, recent studies have revealed that type 2 diabetes is an autoinflammatory disease due to an imbalance of inflammatory cytokine production and related molecular components that cause inflammation. Insulin-like growth factor (IGF) and the insulin-like growth factor-binding protein-3 (IGFBP3) system are known to be involved in the development of experimental diabetic nephropathy, and urinary IGFBP3 protease activity has been observed in patients with type 2 diabetes. A serine protease was found to be responsible for the proteolytic activity in diabetic urine; however, the identity of the precise enzyme remains unknown. We investigated neutrophil proteinase 3 (PR3) to see whether it has specific enzymatic activity associated with insulin-like growth factor-1 and IGFBP3. In our study, both molecules were sufficiently degraded, which leads us to believe that PR3 may induce insulin resistance in the mouse model utilized. In addition, we found that PR3 in the urine of diabetic patients similarly affects insulin resistance. Moreover, PR3-immunized mice had an increase in glucose clearance due to inhibition of PR3 activity. As such, PR3 can be considered as an inflammatory enzyme directly linking inflammation to type 2 diabetes through downregulation of insulin-like growth factor-1/IGFBP3. |
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Authors:
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Suyoung Bae; Jida Choi; Jaewoo Hong; Hyunjhung Jhun; Kwangwon Hong; Taebong Kang; Keeho Song; Sangmin Jeong; Hokee Yum; Soohyun Kim |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-20 |
Journal Detail:
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Title: Endocrine research Volume: - ISSN: 1532-4206 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8408548 Medline TA: Endocr Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Laboratory of Cytokine Immunology, Institute of Biomedical Science and Technology, College of Medicine, Konkuk University , Seoul , Republic of Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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