Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Little definitive data are available concerning the effects of insulin deficiency on the hepatic uptake and biliary excretion of endogenous or xenobiotic substances. To expand our understanding of this area, male Sprague-Dawley rats were pretreated with streptozotocin (45 mg/kg i.v.) to induce uncontrolled diabetes. Four to five weeks later, diabetic rats exhibited elevations in serum glucose (640 +/- 13 mg/dl), biliary glucose (307 +/- 35 mg/dl), urine output (166 +/- 11 ml/24 hr), basal bile flow rate (73 +/- 2 microliter/min/kg), liver weight/body weight ratio and bile acid pool size. Polyphagia and generalized muscle atrophy were also evident. Plasma disappearance and biliary excretion of several organic anions were studied after i.v. administration. There were no differences between control and diabetic rats in the plasma elimination and biliary excretion of eosin, phenol-3,6-dibromphthalein disulfonate and sulfobromophthalein. Although hepatic uptake was unchanged, the biliary excretion of amaranth was decreased 30% in diabetic rats. There were no differences in bile flow rate in control or diabetic rats after administration of these four anions. In contrast, administration of indocyanine green, bromcresol green and rose bengal did not depress bile flow in diabetic rats as was observed in control rats. In addition, the rate of maximal biliary excretion was increased by 390, 240 and 151% for rose bengal, indocyanine green and bromcresol green, respectively. Plasma clearance of rose bengal was 65% higher in diabetic rats. Total body clearance and steady-state volume of distribution values for all other anions were not different after induction of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biliary excretion of organic anions in diabetic rats. 243 94

Phthalate diesters are commonly used as industrial plasticisers, as well as in cosmetics and skin care products, as a result people are constantly exposed to these xenobiotics. Recent epidemiological studies have found a correlation between circulating phthalate levels and type 2 diabetes, whereas animal studies indicate that phthalates are capable of disrupting endocrine signaling. Nonetheless, how phthalates interfere with metabolic function is still unclear. Here, we show that feeding Drosophila males the xenobiotic dibutyl phthalate (DBP) affects conserved insulin- and glucagon-like signaling. We report that raising flies on food containing DBP leads to starvation resistance, increased lipid storage, hyperglycemia, and hyperphagia. We go on to show that the starvation-resistance phenotype can be rescued by overexpression of the glucagon analogue adipokinetic hormone (Akh). Furthermore, although acute DBP exposure in adult flies is able to affect insulin levels, only chronic feeding influences Akh expression. We establish that raising flies on DBP-containing food or feeding adults DBP food affects the expression of homologous genes involved in xenobiotic and lipid metabolism (AHR [Drosophila ss], NR1I2 [Hr96], ABCB1 [MDR50], ABCC3 [MRP], and CYP3A4 [Cyp9f2]). Finally, we determined that the expression of these genes is also influenced by Akh. Our results provide comprehensive evidence that DBP can disrupt metabolism in Drosophila males, by regulating genes involved in glucose, lipid, and xenobiotic metabolism.
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PMID:Dibutyl Phthalate Exposure Disrupts Evolutionarily Conserved Insulin and Glucagon-Like Signaling in Drosophila Males. 2710 Jun 21