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 β-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. Greater augmentation of secretion than of synthesis, occurring when conditions stressful to β-cells were imposed, may have produced the reduction of insulin stores seen among ShamDex and PxDex rats and, as a result of the depleted stores, the unexpectedly low AIRmax in PxDex rats seen at 20 wk after surgery. These findings may be pertinent to investigations of insulin secretion and insulin stores accompanying spontaneous diabetes in animals and humans.
Comparative Modulations of Insulin Secretion, Pancreatic Insulin Content, and Proinsulin mRNA in Rats: Effects of 50% Pancreatectomy and Dexamethasone Administration
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Matthew J Orland, M Alan Permutt; Comparative Modulations of Insulin Secretion, Pancreatic Insulin Content, and Proinsulin mRNA in Rats: Effects of 50% Pancreatectomy and Dexamethasone Administration. Diabetes 1 February 1991; 40 (2): 181–189. https://doi.org/10.2337/diab.40.2.181
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