Comparative modulations of insulin secretion, pancreatic insulin content, and proinsulin mRNA in rats. Effects of 50% pancreatectomy and dexamethasone administration.
These studies compared measurements of in vivo insulin secretion, insulin stores, and insulin synthesis. Rats were studied at 24 wk of age, either 1 or 20 wk after a sham operation (Sham) or 50% pancreatectomy (Px), reducing beta-cell number. By 20 wk after surgery, an adaptation to pancreatectomy was apparent from results of serial glucose tolerance tests, done in a preliminary protocol. Some of the rats also received dexamethasone (ShamDex and PxDex, respectively), imposing insulin resistance. Insulin secretion was assessed with the acute insulin response to arginine under basal (AIRbas) and maximum glucose-potentiated (AIRmax) states. Pancreatic insulin was measured, and insulin synthesis was estimated by measurement of proinsulin mRNA. At 1 wk after surgery, there was no difference among Sham and Px rats in AIRbas, but in the Px rats, expected reductions of AIRmax, pancreatic insulin, and proinsulin mRNA were found. ShamDex rats had a markedly augmented AIRbas and increased AIRmax and proinsulin mRNA. However, pancreatic insulin was reduced both in ShamDex and PxDex rats. At 20 wk after surgery, the predicted adaptation to Px was substantiated by AIRmax and proinsulin mRNA in Px rats not different from those in Sham rats, but pancreatic insulin in the Px rats remained low. AIRbas and proinsulin mRNA were augmented in ShamDex and PxDex rats, but pancreatic insulin was again reduced, and in PxDex rats, low AIRmax and fed hyperglycemia were seen. Linear correlations of AIRbas and AIRmax with proinsulin mRNA were observed over a roughly fourfold range of secretion and synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Orland
M J
MJ
Washington University School of Medicine, St. Louis, Missouri 63110.
Permutt
M A
MA
D000222:Adaptation, Physiological; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D001835:Body Weight; D003907:Dexamethasone / Q000494:pharmacology; D005951:Glucose Tolerance Test; D007328:Insulin / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D009929:Organ Size; D010179:Pancreas / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D010180:Pancreatectomy; D011384:Proinsulin / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D003907:Dexamethasone; D011384:Proinsulin; D001120:Arginine