| Glucose stimulates human beta cell replication in vivo in islets transplanted into NOD-severe combined immunodeficiency (SCID) mice. | |
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MedLine Citation:
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PMID: 20936253 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS/HYPOTHESIS: We determined whether hyperglycaemia stimulates human beta cell replication in vivo in an islet transplant model METHODS: Human islets were transplanted into streptozotocin-induced diabetic NOD-severe combined immunodeficiency mice. Blood glucose was measured serially during a 2 week graft revascularisation period. Engrafted mice were then catheterised in the femoral artery and vein, and infused intravenously with BrdU for 4 days to label replicating beta cells. Mice with restored normoglycaemia were co-infused with either 0.9% (wt/vol.) saline or 50% (wt/vol.) glucose to generate glycaemic differences among grafts from the same donors. During infusions, blood glucose was measured daily. After infusion, human beta cell replication and apoptosis were measured in graft sections using immunofluorescence for insulin, and BrdU or TUNEL. RESULTS: Human islet grafts corrected diabetes in the majority of cases. Among grafts from the same donor, human beta cell proliferation doubled in those exposed to higher glucose relative to lower glucose. Across the entire cohort of grafts, higher blood glucose was strongly correlated with increased beta cell replication. Beta cell replication rates were unrelated to circulating human insulin levels or donor age, but tended to correlate with donor BMI. Beta cell TUNEL reactivity was not measurably increased in grafts exposed to elevated blood glucose. CONCLUSIONS/INTERPRETATION: Glucose is a mitogenic stimulus for transplanted human beta cells in vivo. Investigating the underlying pathways may point to mechanisms capable of expanding human beta cell mass in vivo. |
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Authors:
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H E Levitt; T J Cyphert; J L Pascoe; D A Hollern; N Abraham; R J Lundell; T Rosa; L C Romano; B Zou; C P O'Donnell; A F Stewart; A Garcia-Ocaña; L C Alonso |
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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: 2010-10-09 |
Journal Detail:
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Title: Diabetologia Volume: 54 ISSN: 1432-0428 ISO Abbreviation: Diabetologia Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-07 Completed Date: 2011-05-25 Revised Date: 2012-04-03 |
Medline Journal Info:
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Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: Germany |
Other Details:
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Languages: eng Pagination: 572-82 Citation Subset: IM |
Affiliation:
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Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, 200 Lothrop St, BST E1140, Pittsburgh, PA 15261, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals Apoptosis / physiology Blood Glucose / physiology Cell Proliferation Child Female Humans Hyperglycemia / therapy In Situ Nick-End Labeling Insulin-Secreting Cells / cytology* Islets of Langerhans Transplantation* Male Mice Mice, Inbred NOD Mice, SCID Middle Aged |
| Grant Support | |
ID/Acronym/Agency:
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K08 DK076562/DK/NIDDK NIH HHS; K08 DK076562-05/DK/NIDDK NIH HHS; R01 DK077096/DK/NIDDK NIH HHS; R01 DK077096-05/DK/NIDDK NIH HHS; R01 DK55023/DK/NIDDK NIH HHS; R01 HL063767/HL/NHLBI NIH HHS; U01 DK072473/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose |
| Comments/Corrections | |
Comment In:
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Diabetologia. 2011 Mar;54(3):477-9
[PMID:
21174074
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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