Decrease in insulin-containing secretory granules and mitochondrial gene expression in mouse pancreatic islets maintained in culture following streptozotocin exposure.
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.
Clinical Investigation and Patient Care Branch, National Institute of Dental Research, National Institute of Health, Bethesda 20892.
J E
JE
Moreira
A R
AR
Hand
L A
LA
Håkan Borg
S
S
Sandler
M
M
Welsh
N
N
Welsh
D L
DL
Eizirik
D000818:Animals; D002478:Cells, Cultured; D003573:Cytochrome b Group / Q000096:biosynthesis* / Q000235:genetics; D003594:Cytoplasmic Granules / Q000187:drug effects* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013311:Streptozocin / Q000494:pharmacology*
D003573:Cytochrome b Group; D004272:DNA, Mitochondrial; D007328:Insulin; D012333:RNA, Messenger; D013311:Streptozocin; D005947:Glucose