AJP - Endocrinology and Metabolism, Vol 256, Issue 2 E303-E308, Copyright © 1989 by American Physiological Society
Proinsulin mRNA levels in fasting and fed ADX rats: evidence for an indirect effect of glucocorticoids
F. T. Fiedorek Jr and M. A. Permutt
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
To determine whether glucocorticoids are required to maintain pancreatic
proinsulin mRNA levels during dietary manipulation, rats were
adrenalectomized (ADX) or sham operated (SO) and subsequently fasted or
pair fed for 2 days. Proinsulin mRNA concentrations were 54 +/- 8% lower (P
less than 0.05) in fed ADX rats and 47 +/- 10% lower (P less than 0.01) in
fasted ADX rats relative to values in fed and fasted SO rats, respectively.
When ADX rats were fasted for 24 h and either refed 20% sucrose for 30 h or
injected with dexamethasone (DEX) 0.125 mg/kg ip every 12 h for three
doses, circulating plasma glucose levels were restored and pancreatic
proinsulin mRNA concentrations rose 3.3 and 2.7-fold, respectively (each P
less than 0.05). Plasma glucose and proinsulin mRNA levels (n = 40) were
correlated (r = 0.58, P less than 0.0001). We conclude that the regulation
of proinsulin mRNA concentration does not absolutely require endogenous
glucocorticoids, since either adequate sucrose intake in ADX rats or
physiological glucocorticoid responses in fasted rats suffice to restore
pancreatic mRNA concentrations. It appears that glucocorticoid stimulation
of pancreatic proinsulin mRNA levels is mediated indirectly through its
regulation of glucose metabolism.
