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Effect of chronic rosiglitazone, metformin and glyburide treatment on β‐cell mass, function and insulin sensitivity in mZDF rats
Author(s) -
Atkinson L. L.,
McDonaldDyck C.,
Benkoczi C.,
Finegood D. T.
Publication year - 2008
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2007.00811.x
Subject(s) - rosiglitazone , medicine , endocrinology , metformin , insulin , diabetes mellitus
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.