Decrease in insulin-containing secretory granules and mitochondrial gene expression in mouse pancreatic islets maintained in culture following streptozotocin exposure |
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Authors: | Jorge E Moreira Arthur R Hand L A Håkan Borg Stellan Sandler Michael Welsh Nils Welsh Décio L Eizirik |
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Institution: | 1. Clinical Investigation and Patient Care Branch, National Institute of Dental Research, National Institute of Health, Bethesda, MD, USA 4. Department of Medical Cell Biology, Uppsala University, Biomedicum, P.O. Box 571, S-75123, Uppsala, Sweden
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Abstract: | We have previously described a preferential reduction in the secretory response to nutrient secretagogues in pancreatic mouse
islets maintained in culture after in vitro exposure to streptozotocin (SZ). This reduction was associated with an impaired
substrate metabolism at the mitochondrial level. To further clarify this issue, mouse pancreatic islets were exposed in vitro
to 2.2 mM SZ for 30 min. At 4 h after SZ treatment ultrastructural changes were apparent in the endoplasmic reticulum and
Golgi areas of the B-cells. However, 2 and 6 days following SZ exposure the B-cells appeared well preserved, except for a
marked decrease in the number of insulin-containing secretory granules. A morphometric analysis of the B-cells 6 days after
SZ exposure showed a normal B-cell size and a normal volume fraction of B-cell mitochondria. However, there was a decrease
in total islet size and a 13% decrease in the volume fraction of B-cells in the islets. These mouse islets exhibited a decreased
content of the mitochondrial DNA-encoded cytochrome b mRNA, as evaluated by dot-blot analysis. As a whole, the data obtained
indicate that SZ treatment does not induce a decrease in the number of mitochondria or long-lasting ultrastructural damage
to this organelle. However, there is a clear decrease in the cytochrome b mRNA, suggesting that SZ can induce damage to the
mitochondrial DNA. |
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Keywords: | Streptozotocin Pancreatic islets Insulin release Cytochrome b mRNA Ultrastructure |
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