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)

Twenty days after the onset of alloxan-induced diabetes, a villous hyperplasia has developed in the intestines of rats having free access to food. The transformation is characterised by a considerable increase in the area of the villous surface, caused by an enhanced mitotic activity in the crypts. The absorption of glucose or methionine by jejunal loops, whether expressed in terms of serosal area or villous area, is unchanged at this stage. On the other hand, the specific activity of certain disaccharidases and dipeptidases in crude mucosal homogenates is greater in diabetic animals, but quantitative histochemistry revealed no changes in the activities of alkaline phosphatase, leucine amino-peptidase and non-specific esterase in the individual enterocytes. Thus the biochemical changes may simply reflect the hyperplasia of the mucosa. The blood sugar level does not appear to be directly responsible for the mucosal transformation; however, the positive correlation between the daily food intake and the villus height suggests a role of hyperphagia and consequent increased luminal nutrition in the development of the hyperplasia.
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PMID:Structural and functional studies on the transformation of the intestinal mucosa in rats with experimental diabetes. 88 18

It is well known that adrenalectomy (ADX) reverses the eating and energy balance disturbances in a variety of models of obesity associated with elevated food intake. We have previously demonstrated enhanced functional activity in the small intestine of neonatally monosodium glutamate-treated (MSG) obese rats despite the absence of overeating and we concluded that these changes might also contribute to the development of MSG obesity. The objective of the present experiments was to investigate whether ADX would affect the small intestinal functions and whether their changes would counteract attenuation or prevention of obesity development in MSG rats. Therefore the investigation was carried out in MSG-obese Wistar male rats and untreated intact rats adrenalectomized on day 40, as well as in lean littermates of MSG rats and intact rats subjected to Sham-ADX surgery. All animals had free access to a standard pellet diet after weaning. At the age of 80 days, body mass, body fat content and food consumption as well as changes of the brush-border-bound duodenal and jejunal alkaline phosphatase (AP), the dipeptidyl(amino)peptidase IV (DPP IV) and maltase activity were measured. During the postoperative period, ADX resulted in a significant decrease of mass gain in both MSG and control rats (P<0.05). ADX fully prevented the development of obesity in MSG rats (significantly decreased epididymal+retroperitoneal fat pad mass, P<0.05) and increased mean daily food intake (P<0.001). These effects were only minimal in the ADX controls suggesting that enhanced adrenal secretion is involved in the expression of MSG obesity and its complications. The AP activity in obese MSG rats was increased by about 21 % (P<0.01) in both intestinal segments when compared to the lean controls, whereas no parallel variations in the activities of DPP IV and maltase were observed in the intestinal parts mentioned. In MSG rats, ADX significantly reduced the AP activity in the duodenum and jejunum (P<0.01). A similar tendency was also seen in the DPP IV activity of adrenalectomized MSG rats as well as in lean control rats. Nevertheless, no significant effect of adrenal withdrawal on maltase activity was found. These results indicate that the decrease of enzyme activities in the small intestine and the different effectiveness of nutrient absorption might be a significant factor preventing the development of excess adiposity in glutamate-treated rats. This information contributes to a better understanding of the importance of small intestinal function for the development of obesity and its maintenance in later life.
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PMID:Effect of adrenalectomy on the activity of small intestine enzymes in monosodium glutamate obese rats. 1531 1

Deletion of the Prolyl Endopeptidase-like (PREPL) gene has been described in three contiguous gene deletion syndromes at the 2p21 locus and current developments in high resolution microarrays and whole genome sequencing will no doubt soon result in the identification of isolated PREPL deficiency. But by comparing the differences in phenotypes with the number of genes deleted, the contribution of PREPL deficiency can already be deduced. Homozygous or compound heterozygous loss of PREPL is predicted to cause neonatal hypotonia and severe feeding problems. Failure to thrive usually persists for several years, followed by a period of hyperphagia and excessive weight gain. Growth retardation is usually observed, which responds well to growth hormone therapy. In addition, minor facial dysmorphism, nasal speech, viscous saliva, hypergonadotropic hypogonadism and learning problems are frequently observed. How PREPL deficiency causes these clinical manifestations remains unknown. PREPL is highly expressed in brain and based on gene coexpression network architecture it has been placed in a group enriched with markers of neurons and synaptic proteins. PREPL is predicted to be a serine oligopeptidase based on its homology with prolyl endopeptidase (PREP) and the presence of an active catalytic triad. However, until now no substrates have been found. Recent observations that PREP has non-catalytic functions in the cytoplasm through interactions with its amino- terminal propeller domain, suggests that of PREPL may also have biological functions independent of its predicted peptidase activity. This raises the possibility that PREP and PREPL are homologous, not just by name but also by nature.
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PMID:PREPL, a prolyl endopeptidase-like enzyme by name only?--Lessons from patients. 2122 27

Background: Thymoquinone (TQ) is a safe nutrient isolated from the seeds or volatile oil extract of Nigella sativa. In addition to its benefits in glucose regulation, TQ improves feeding disorders in diabetic animals. Glucagon-like peptide-1 (GLP-1) analogs improve glycemic control and ameliorate obesity or hyperphagia. Therefore, the present study aimed to investigate the role of GLP-1 in TQ-induced anorexia. Method: Type 2 diabetes was induced in rats by nicotinamide and streptozotocin injection. TQ was orally administered to diabetic rats at different doses for 45 days. Following TQ treatment, changes in serum glucose levels, GLP-1 concentration, body weight, food intake, and water intake were determined. To further explore the interaction between GLP-1 and TQ, the inhibitor of dipeptidyl peptidase 4, sitagliptin and the GLP-1 receptor antagonist exendin 9-39 (Ex 9-39) were separately administered to TQ- or vehicle-treated diabetic rats. Results: TQ treatment attenuated hyperglycemia and reduced hyperphagy and water intake in streptozotocin-induced diabetic rats in a dose-dependent manner. Moreover, TQ treatment elevated plasma GLP-1 levels compared to those in control rats. The effects of TQ were enhanced by treatment with sitagliptin and reduced by the injection of Ex 9-39 into the brain. In contrast, similar treatment with another antioxidant (either ascorbic acid or N-acetylcysteine) produced the same anorexic effect as TQ without changing the plasma GLP-1 levels in diabetic rats. Therefore, TQ attenuated hyperphagy while increasing plasma GLP-1 levels and had antioxidant-like effects. Conclusion: TQ increased endogenous GLP-1 levels to reduce hyperphagy in diabetic rats.
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PMID:GLP-1 mediates the modulating effect of thymoquinone on feeding behaviors in diabetic rats. 3135 23