To evaluate the effect of oral antidiabetic drugs on glucocorticoid induced diabetes mellitus in albino rats.
Glucocorticoids induce diabetes mellitus mainly by increasing peripheral insulin resistance. There are different factors, which lead to excess of glucocorticoids, stress being one of them 1. Obesity is the main feature of the epidemic of type 2 diabetes mellitus. Beta hydroxysteroid dehydrogenase 1 enzyme is expressed in increased quantity in the visceral fat of these patients. Transgenic mice expressing around 20% excess of this enzyme develop the typical features of metabolic syndrome, viz. Obesity, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, hypertension etc., This enzyme converts inactive cortisone to active cortisol 2. Diabetes induced by large dose of dexamethasone poses a challenging situation in clinical practice 3. All these factors led us to conduct this study.
Glibenclamide was not effective in reducing blood sugar level in doses of 5mg/kg as well as 15mg/kg per day. Metformin 500mg/kg & Rosiglitazone 8mg/kg reduced fasting glucose as well as GTT glucose levels. Intraperitoneal glucose test was conducted by injecting 2.5 g/kg of glucose & blood glucose level was measured 1 hour later using one touch glucometer & strips.
In vitro studies have shown that dexamethasone dose dependently inhibits insulin release mediated by glucose as well as other insulin releasers including Tolbutamide 4. Therefore insulin releasers are not effective in high dose dexamethasone induced diabetes mellitus. When glucose is given intraperitoneally, only a drug with systemic effect other than insulin releasers are effective. The results in our study agree with the invitro study. Thus it is inferred that high dose dexamethasone induced diabetes combined with intraperitoneal glucose tolerance test may be a suitable model to screen insulin sensitisers.