Melior Discovery metabolic
db/db Mouse Model of Type II Diabetes
Type II diabetes is characterized by high blood glucose levels in the presence of normal or elevated serum insulin levels. There are many animal models of type II diabetes that involve administering high levels of glucose to otherwise normoglycemic mice (see OGTT mouse model). db/db mice express mutations in leptin receptor that lead to decreased insulin receptor sensitivity and subsequent increased levels of blood glucose, decreased β-cell function, increased obesity and elevated HBA1c levels. Compounds from several structural classes can effectively regulate this hyperglycemic response including sulfonylureas, thiazoladinediones (PPARγ agonists; glitazones) and metformin (glucophage). These drug classes are also clinically approved for use in humans.
The above data illustrate the effects of rosiglitazone, an antidiabetic drug in the thiazolidinedione class, across time in db/db mice. Initially both vehicle and rosiglitazone treated mice exhibit similar blood glucose levels (days 0 & 5). However, by day 10 mice treated with rosiglitazone have significantly decreased blood glucose levels relative to vehicle treated mice. This effect is maintained throughout the study, illustrating the ability of antidiabetic drugs to decrease blood glucose in mice with diabetic like physiology. Data are mean ± SEM; ***p<0.001 compared to baseline, +++p<0.001 compared to vehicle.
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