Detrimental effect of protracted hyperglycaemia on beta-cell neogenesis in a mouse murine model of diabetes.
OBJECTIVE
Previous studies have shown that new beta cells differentiate from intra-islet precursors in pancreatic islets of mice in which diabetes is induced by injecting a high dose of the beta-cell toxin streptozotocin. Moreover, the re-establishment of euglycaemia by insulin therapy 1 day after streptozotocin treatment improved the process of regeneration. We sought to assess whether a 1-week delay in the restoration of euglycaemia would affect beta-cell regeneration.


METHODS
Adult CD-1 mice were injected with 200 mg/kg of streptozotocin. One group of mice remained hyperglycaemic throughout the experiment while a second group became normoglycaemic following the administration of insulin therapy 1 week after the injection of streptozotocin. Pancreata removed at different times after treatment were processed for visualization ofbeta precursor-cell markers and insulin by confocal microscopy.


RESULTS
New beta cells appeared in islets of streptozotocin-treated mice after restoration of normoglycaemia. Like islets of streptozotocin mice in which blood glucose concentrations were rapidly restored, islets of mice that became normoglycaemic 1 week after streptozotocin treatment also had two potential insulin precursor cell types. Protracted hyperglycaemia however, had several harmful effects on insulin cell neogenesis, such as a reduction in the number of euglycaemic mice with successful beta-cell regeneration and a decrease in the number and survival of the newly differentiated insulin-containing cells.


CONCLUSIONS
These results indicate that islets gradually lose their regenerative potential when they are exposed to high circulating glucose concentrations for an extended period of time.
Guz
Y
Y
Department of Anatomy and Cell Biology, State University of New York, Health Science Center at Brooklyn, 11203, USA.
Torres
A
A
Teitelman
G
G
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002452:Cell Count; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D051273:Glucose Transporter Type 2; D006943:Hyperglycemia / Q000097:blood / Q000209:etiology* / Q000473:pathology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D013997:Time Factors
D001786:Blood Glucose; D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins