Proinsulin mRNA levels in fasting and fed ADX rats: evidence for an indirect effect of glucocorticoids.
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.
Fiedorek
F T
FT
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Permutt
M A
MA
D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D004435:Eating; D005215:Fasting; D005938:Glucocorticoids / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D009929:Organ Size; D010179:Pancreas / Q000033:anatomy & histology; D011384:Proinsulin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D012333:RNA, Messenger; D011384:Proinsulin