| Chronic Pulsatile Hyperglycemia Reduces Insulin Secretion and Increases Accumulation of Reactive Oxygen Species in Fetal Sheep Islets. | |
| | |
MedLine Citation:
|
PMID: 22182602 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Children from diabetic pregnancies have a greater incidence of Type 2 diabetes. Our objective was to determine if exposure to mild-moderate hyperglycemia, modeling managed diabetic pregnancies, affects fetal β-cell function. In sheep fetuses β-cell responsiveness was examined after two weeks of sustained hyperglycemia with 3 pulses/day, mimicking postprandial excursions, and compared to saline-infused controls (n=10). Two pulsatile hyperglycemia treatments were studied: mild (mPHG, n=5) with +15% sustained and +55% pulse; and moderate (PHG, n=10) with +20% sustained and +100% pulse. Fetal glucose-stimulated insulin secretion and glucose potentiated arginine insulin secretion were lower (P<0.05) in PHG (0.86±0.13 and 2.91±0.39 ng/ml plasma insulin) but not mPHG fetuses (1.21±0.08 and 4.25±0.56 ng/ml) compared to controls (1.58±0.25 and 4.51±0.56 ng/ml). Islet insulin content was 35% lower in PHG and 35% higher in mPHG versus controls (P<0.01). Insulin secretion and maximally stimulated insulin release were also reduced (P<0.05) in PHG islets due to lower islet insulin content. Isolated PHG islets also had 63% greater (P<0.01) ROS accumulation at 11.1 mmol/L glucose than controls (P<0.01), but oxidative damage was not detected in islet proteins. PHG fetuses showed evidence of oxidative damage to skeletal muscle proteins (P<0.05) but not insulin resistance. Our findings show that PHG induced dysregulation of islet ROS handling and decreased islet insulin content, but these outcomes are independent. The β-cell outcomes were dependent on the severity of hyperglycemia because mPHG fetuses had no distinguishable impairments in ROS handling or insulin secretion but greater insulin content. |
| | |
Authors:
|
Alice S Green; Xiaochuan Chen; Antoni R Macko; Miranda J Anderson; Amy C Kelly; Nathaniel J Hart; Ronald M Lynch; Sean W Limesand |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-12-19 |
Journal Detail:
|
Title: The Journal of endocrinology Volume: - ISSN: 1479-6805 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2011-12-20 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0375363 Medline TA: J Endocrinol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
A Green, Animal Sciences, University of Arizona, Tucson, United States. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Preparation and characterization of 5-fluorouracil pH-sensitive niosome and its tumor-targeted evalu...
Next Document: Matrix metalloproteinase-9 expression in folliculostellate cells of rat anterior pituitary gland.