Dexamethasone during late gestation exacerbates peripheral insulin resistance and selectively targets glucose-sensitive functions in beta cell and liver

We examined whether low-dose dexamethasone administration during late pregn ancy modifies hepatic and/or peripheral insulin action or glucose-stimulate d insulin secretion. Dexamethasone (100 mug/kg maternal body weight/d) was administered via an osmotic minipump from d 14-19 of gestation. Maternal gl ucose-insulin homeostasis was assessed on d 19 of pregnancy in the postabso rptive state. Insulin secretion and glucose tolerance was assessed after iv glucose, and insulin action examined during insulin infusion at euglycemia . Dexamethasone treatment during late pregnancy elicited fasting hyperinsul inaemia (by 88%; P < 0.001) and hyperglycaemia (by 20%; P < 0.05), and enha nced endogenous glucose production (by 29%; P < 0.001). Insulin secretion a nd rates of glucose disappearance after iv glucose were greatly impaired (b y 44% and 39% respectively; P < 0.05). Suppression of endogenous glucose pr oduction by insulin was enhanced by dexamethasone treatment, but insulin's ability to promote glucose clearance was diminished. We demonstrate that ex cess maternal glucocorticoids during late pregnancy impairs glucose-stimula ted insulin secretion and insulin-simulated glucose clearance but enhances insulin's ability to suppress endogenous glucose production. The data also indicate that elevated maternal glucocorticoids impair adaptations of the e ndocrine pancreas to pregnancy in vivo in that insulin hypersecretion in re sponse to deteriorating peripheral insulin action is no longer apparent, le ading to impaired glucose tolerance.