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- Title
Effect of chronic rosiglitazone, metformin and glyburide treatment on β-cell mass, function and insulin sensitivity in mZDF rats.
- Authors
Atkinson, L. L.; McDonald-Dyck, C.; Benkoczi, C.; Finegood, D. T.
- Abstract
Here we investigate the effect of rosiglitazone (RSG), metformin (MET) and glyburide (GLIB) on plasma glucose levels, β-cell mass, function and insulin sensitivity in 10-week-old diabetic male Zucker diabetic fatty (mZDF) rats using quantitative morphometry and a mathematical model β-cell mass, insulin and glucose kinetics (βIG). At treatment start, 10-week-old diabetic mZDF rats were severely hyperglycaemic and had very low β-cell function (insulin secretory capacity). RSG treatment significantly lowered plasma glucose levels in 67% of the mZDF rats. MET was effective at lowering plasma glucose levels in 33% of the mZDF rats, while GLIB was completely ineffective at lowering blood glucose levels in 10-week-old mZDF rats. RSG treatment prevented the fall in β-cell mass after 6–8 weeks of treatment accompanied by a significant decrease in β-cell death while MET treatment had no effect on β-cell mass. RSG treatment increased insulin sensitivity 10-fold, increased β-cell function fivefold and modestly increased β-cell mass 1.4-fold. MET treatment increased insulin sensitivity fourfold, with no significant effect on β-cell function or mass. Although RSG treatment was highly successful in lowering plasma glucose levels, the 33% of mZDF rats that did not respond to the treatment had significantly lower β-cell function prior to treatment start compared with the responder group. Thus, the low level of β-cell function at treatment start may explain why none of these agents were completely effective at lowering blood glucose levels in 10-week-old diabetic mZDF rats. Nevertheless, these data suggest that the preservation of β-cell mass and improvement in β-cell function play a role in the overall beneficial effect of RSG in 10-week-old diabetic mZDF rats.
- Subjects
INSULIN resistance; B cell differentiation; METFORMIN; CELL death; LABORATORY rats; BLOOD sugar; TYPE 2 diabetes
- Publication
Diabetes, Obesity & Metabolism, 2008, Vol 10, Issue 9, p780
- ISSN
1462-8902
- Publication type
Article
- DOI
10.1111/j.1463-1326.2007.00811.x