Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nature and mechanism of the pancreatic exocrine dysfunction in diabetes mellitus were evaluated in vitro using isolated pancreatic acini prepared from streptozotocin-induced diabetic rats. The content of amylase and ribonuclease in diabetic acini was approximately 0.5 and 50% of the normal content, respectively. Further, reduced amounts of both enzymes were secreted by diabetic acini in response to both cholecystokinin (CCK) and carbamylcholine. However, when enzyme secretion was normalized relative to initial acinar contents, both normal and diabetic acini released enzymes at a comparable maximal rate. The time course of the release of these enzymes, and newly synthesized protein were similar in both acini. In normal acini, the effect of CCK was maximal at a concentration of 100 pM; higher concentrations led to submaximal enzyme release. The dose-response curve in diabetic acini was similarly shaped, but shifted three-fold towards higher concentration. The mobilization of cellular Ca(2+) in response to CCK was also shifted. In contrast to these results with CCK, the dose-response curve to carbamylcholine was unaltered by diabetes. The observed effects were confirmed to be due to insulin deficiency and not due to direct toxic effect of streptozotocin on acinar cells or malnutrition. Streptozotocin had no acute effect on acini when measured 24 h after administration, and alloxan, another beta cell toxin, induced similar changes in acinar enzyme content and secretory response. Moreover, the administration of exogenous insulin to diabetic rats returned the content of pancreatic amylase and the secretory response to CCK towards normal. Starvation for 48 h, although inducing a significant weight loss, did not mimic the effects of diabetes. The present studies demonstrate two major abnormalities in pancreatic exocrine secretion in the diabetic rat: (a) the content of certain digestive enzymes is markedly altered, leading to an altered amount of zymogen secretion, (b) the sensitivity to CCK is selectively reduced, most likely related to a defect in receptor activated transmembrane signaling.
 ...
PMID:Effect of diabetes mellitus on the regulation of enzyme secretion by isolated rat pancreatic acini. 617 17

Diabetes alters the level of insulin-like growth factor I (IGF-I) mRNA in tissues of postnatal animals, but the impact of maternal diabetes or gestational diabetes on IGF-I mRNA abundance in fetal tissues has not been examined. Pregnant pigs were injected with either buffer or alloxan (50 mg/kg) at day 75 of gestation to induce diabetes. Fetal tissue samples were collected at day 105 of gestation, and IGF-I mRNA abundance (densitometric units/10 micrograms total RNA) were estimated by specific ribonuclease protection assay. Fetal glucose and IGF-I concentrations were increased 166 and 34%, respectively, by maternal diabetes. Maternal diabetes induced an increase in abundance of IGF-I mRNA in fetal skeletal muscle, liver, heart, kidney, and placenta. IGF-I mRNA levels were depressed by maternal diabetes in fetal adipose tissue and brain compared with the respective tissues from fetuses of control pigs. These data indicate that circulating levels of IGF-I and the steady-state levels of IGF-I mRNA in fetal tissues can respond to the metabolic and endocrine alterations occurring during maternal diabetes. The large variation in expression and degree of response among fetal tissues indicates that the fetus experiences tissue-specific regulation of IGF-I expression during development.
 ...
PMID:Alteration in IGF-I mRNA content of fetal swine tissues in response to maternal diabetes. 797 70