Tissue-specific alterations in somatostatin mRNA accumulation in streptozocin-induced diabetes.
In streptozocin-induced diabetes in rats, there is a marked increase in the content and release of immunoreactive somatostatin (SLI) from the pancreas and upper gut. To elucidate whether these SLI changes are associated with alterations in somatostatin gene transcription, we measured somatostatin mRNA (SmRNA) accumulation in these and other SLI-producing tissues. Pancreas, stomach, jejunum, hypothalamus, and cerebral cortex were removed from control rats, 6-wk-diabetic rats, and diabetic rats treated with insulin for 6 wk. Total RNA was isolated by centrifugation through CsCl and fractionated on agarose gels. A sensitive radiodensitometric hybridization assay was used to determine SmRNA levels in absolute amounts by in vitro synthesized sense-strand RNA as a quantitative standard and antisense cRNA as a specific probe. SLI was determined by radioimmunoassay. SmRNA exhibited size heterogeneity between the different control and diabetic tissues. A 2- to 3-fold increase in total SmRNA was found in pancreas and stomach of the diabetic rats that suppressed toward normal with insulin treatment. These two tissues also exhibited significant 1.6- to 2.6-fold increases in SLI, respectively. The remaining tissues showed no diabetes-related changes in SLI or SmRNA. We conclude that in insulinopenic diabetes, tissue SLI and SmRNA accumulation undergo parallel changes; are increased in pancreas and upper gut, reflecting augmented somatostatin synthesis; are reciprocally related to insulin acting directly or indirectly on somatostatin-producing cells; and are unchanged in the lower gut and brain, suggesting tissue-specific regulation of somatostatin gene transcription in diabetes.
Papachristou
D N
DN
Fraser Laboratories, McGill University, Montreal, Quebec, Canada.
Pham
K
K
Zingg
H H
HH
Patel
Y C
YC
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D012313:RNA / Q000235:genetics; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013004:Somatostatin / Q000235:genetics*; D014158:Transcription, Genetic
D016372:RNA, Antisense; D012333:RNA, Messenger; D013004:Somatostatin; D012313:RNA