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)

Diabetes mellitus was tentatively diagnosed in a black-footed ferret with polyuria, polydipsia, polyphagia, dehydration, and weight loss. Laboratory findings (marked hyperglycemia (724 mg/100 ml), glycosuria, and ketonuria) and the subsequent favorable response to insulin therapy confirmed the diagnosis. Although lesions were not observed in the pancreas, gross and histologic findings concomitant with diabetes mellitus included arteriosclerosis, with calcification of the aorta and other major vessels; mild necrotizing hepatitis; and mild proliferative glomerulonephritis. A perineal adenocarcinoma, with metastasis to an internal iliac lymph node, was an incidental finding. Special stains demonstrated adequate numbers of beta cell granules in the islets of Langerhans. Thus, the diabetes was apparently due to a lack of release of the synthesized insulin or to diminished effectiveness of the secreted insulin.
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PMID:Diabetes mellitus in a black-footed ferret. 92 62

In ob/ob mice a 12-wk period of food restriction led to a reduced rate of somatic growth and a decreased lean body mass, along with small but reliable reductions in systemic immunoreactive insulin levels and evidence of increased insulin sensitivity. However, no effects of limited access to food were noted on the basal hyperglycemia, the elevated percent carcass lipid, or on the significantly higher levels of serum corticoids that occur in obese animals. These data indicate that hyperphagia alone is not responsible for the maintenance of many of the commonly reported characteristics of the obese-hyperglycemic syndrome, but do not exclude the contribution of factors secondary to the quantity of ingested food. Additionally, the present data lend support to recent work suggesting that chronic hyperinsulinemia or an elevated set point of total carcass lipid may be instrumental in the development of this syndrome.
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PMID:Effects of limited food intake on the obese-hyperglycemic syndrome. 93 35

Destruction of the ventromedial hypothalamic nuclei (VMN) in the weanling rat without injury to the median eminence results in a series of somatic, endocrine, and metabolic changes that are characterized by normal food and water intake but decreased linear growth, normal body weight but increased carcass fat and reduced carcass protein, lean body mass, and water. The endocrine alterations comprise hyperinsulinemia in the face of normoglycemia, hypertriglyceridemia and hypercholesterolemia and reduced growth hormone levels. The metabolic changes include greater oxidation of glucose and incorporation into lipid and reduced palmitate oxidation but increased incorporation into lipid. Weanling rats with VMN lesions are normophagic in absolute terms, relative to body weight and per metabolic unit, but their nocturnal feeding and weight gain cycles are disrupted and their locomotor activity is reduced. The VMN are involved in the long-term control of feeding - as in the mature rat - as shown by intragastric preloading studies and dietary density manipulation, glucose preference tests and intraperitoneal injections with glucose. Hyperinsulinemia and hypertriglyceridemia are present four days after the VMN operation in the presence of subnormal food intake and plasma glucose levels. Manipulations of the fat content of the diet revealed that the hyperlipidemia is of both endogenous and exogenous origin and that lipoprotein lipase is increased; a 48-hour fast reduced the hyperlipidemia to control levels, however. This suggests that weanling VMN rat tissue may have an impaired ability to take up circulating lipid. An increased incorporation of glycerol into lipid may be due to induction of glycerokinase by hyperinsulinemia. Adipose tissue of weanling VMN rats showed glycerokinase by hyperinsulinemia. Adipose tissue of weanling VMN rats showed neither depressed lipolysis nor diminished lipolytic activity per milligram of tissue protein. Glucose oxidation and incorporation into adipose tissue is increased in several tissues in vitro and there is enhanced glucose disappearance from plasma and incorporation into tissue lipids in vivo. These changes develop within a short time after lesion production and persist at least partially up to six months: glucose utilization in liver increases already four hours after the operation whereas it takes 72 hours to commence in adipose tissue. Insulin resistance is not apparent either in vivo or in vitro. The decreased growth hormone levels are not critical to the metabolic changes, nor is the hyperinsulinemia totally necessary. The metabolic changes also appear on several different types of diet and persist with fasting. The latter does not reduce insulin sensitivity of VMN rat tissues, wheras it does so in normal rats. Mature rats developed the same metabolic changes even in the absence of hyperphagia. The metabolic alterations can be blocked by pharmacologic doses of glucocorticoids, but are enhanced by the administration of estrogen...
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PMID:Origin of endocrine-metabolic changes in the weanling rat ventromedial syndrome. 95 Jun 80

Insulin resistance of diaphragms of ob/ob mice has been repeatedly demonstrated previously both in vitro and in vivo. In the present study, transport and metabolism of glucose with and without insulin stimulation were compared in a skeletal muscle more likely than diaphragm or heart to be representative of the overall striated muscle mass, i.e. isolated soleus muscle. Compared with soleus muscle from lean controls, unstimulated lactate release in the presence of exogenous glucose was depressed from 16.2 to 12.3 nmol/60 min per mg wet wt in soleus from ob/ob mutants; glycolysis was decreased from 6.6 to 3.7 and [14C]glucose oxidation to 14CO2 from 0.90 to 0.33 nmol glucose/60 min per mg wet wt. Uptake of 2-deoxyglucose (2-DOG), both with and without insulin, was very much less for soleus from ob/ob than from lean mice, at 2-DOG concentrations ranging from 0.1 to 10 mM, and in mice of 6-15 wk. When 2-DOG concentration was 1 mM, its basal uptake was 0.53 nmol/30 min per mg wet wt for soleus of ob/ob as against 0.96 for soleus of lean mice. The absolute increment due to 1 mU/ml insulin was 0.49 in muscle of ob/ob as against 1.21 in that of lean mice. When the resistance to insulin action was decreased by pretreatment in vivo by either streptozotocin injection or fasting, the decreased basal 2-DOG uptake of subsequently isolated soleus muscle was not improved. Inhibition of endogenous oxidation of fatty acids by 2-bromostearate, while greatly increasing 14CO2 production from [14C]glucose, did not affect basal [5-3H]glucose metabolism or 2-DOG uptake. It is suggested that transport and/or phosphorylation of glucose under basal, unstimulated conditions are depressed in soleus muscle of ob/ob mice, whether or not resistance to insulin and hyperinsulinemia are also present. Although the origin of the decreased basal glucose uptake remains unknown it might be related to a similar decrease in basal glucose uptake by ventromedial hypothalamic cells, an event presumably resulting in a tendency to hyperphagia. Decreased basal glucose uptake by soleus muscle of ob/ob mice might explain the hyperglycemia, and hence partly the hyperinsulinemia and excessive fat deposition of those animals.
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PMID:Decreased basal, noninsulin-stimulated glucose uptake and metabolism by skeletal soleus muscle isolated from obese-hyperglycemic (ob/ob) mice. 99 31

The effects of bilateral lesions of the ventral noradrenergic bundle (VNA) were studied in male rats. In contrast to data reported by others, hyperphagia and obesity were not observed following VNA lesions. Indeed, except for a depression during the first three postoperative days, food intake (FI) of the VNA lesioned animals (VNAL) was normal. Interestingly, the body weight (BW) of the VNAL was significantly reduced compared to the controls, and a pair feeding study indicated that this depression of BW was not due to their FI. Computation of FI per metabolic size showed that the VNAL actually had a significantly increased FI compared to the controls. After a two day fast the VNAL lost more metabolic size than controls and upon refeeding they defended their pre-fast BW. The VNAL rats showed normal body composition and circulating glucose, insulin and prolactin. They had reduced free fatty acids, triglycerides, growth hormone and body length. The data suggest that the mesencephalon influences BW set point, some metabolites and possibly overall metabolism.
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PMID:Mesencephalic lesions resulting in normophagia, reduced weight and altered metabolism. 99 50

The metabolic effect of ventromedial hypothalamic (VMH) lesions, which are known to cause hyperphagia and obesity, has been studied in rats kept on a controlled light and food regimen. The animals were sacrificed at 4 different times during the second postoperative day. A feeding-induced hypersecretion of insulin was found to the VMH-lesioned animals. It was accompanied by a marked hypoglycemia as compared to the control groups during the feeding period. The glycogen content of liver and diaphragm in the lesioned groups is increased as compared to the controls during the same period. The VMH-lesioned animals showed hypertriglyceridemia both in the fed and fasted state, whereas the postabsorptive plasma levels of free fatty acids and glycerol were decreased. An increased level of urea was observed in all lesioned groups. This is in accordance with the demonstrated protein catabolism which follows VMH lesions.
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PMID:The effect of ventromedial hypothalamic lesions on metabolism and insulin secretion in rats on a controlled feeding regimen. 102 15

Young, adult, female Sprague-Dawley rats were fasted for 18 h and then given a single s.c. injection of alloxan (10 mg/100 g body weight) which promptly induced a severe state of diabetes. The animals were killed at frequent time intervals during the 7-day study period in order to record the dynamic changes in their capacity for adrenal steroidogenesis and secretion as measured by fluorometric determination of their circulating corticosterone (Cmpd B) levels as well as by thin layer chromatographic identification of cortical lipid moieties used for steroidogenesis. In addition to severe polydypsia, polyuria and polyphagia, these animals manifested super-normal glucose, triglycerides, free fatty acids and cholesterol in their blood, severe hepatic steatosis, adrenal hyperplasia with lipid depletion from the mineralocorticoid producing z. glomerulosa, thymus gland involution and complete degranulation of their insulin producing islet beta cells. Despite an initial high output of Cmpd B and despite progressive cortical hyperplasia, the serum Cmpd B levels became reduced and many of the animals succumbed suddenly, due most likely to inadequate adrenocortical steroidogenesis. Adrenocortical lipids showed a progressive accumulation of free fatty acids, di- and triglycerides, suggesting that some lipid enzymatic defect could be responsible for the lack of conversion of these lipid entities essential for proper steroidogenesis.
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PMID:Adrenal glandular lipids and circulating corticosterone in severely diabetic rats. 117 54

Parasagittal knife cuts through the perifornical hypothalamus either medial or lateral to the fornix produced hyperphagia and obesity and altered the rat's ingestive responses to dilute glucose solutions. The lateral knife cut rats drank less dilute glucose solution under both nondeprived and food deprived conditions and displayed less of a feeding suppressive response to glucose ingestion compared to controls. The lateral cut rats were also deficient in their feeding response to insulin-induced hypoglycemia, although their altered sensitivity to glucose and insulin did not appear to be causally related. The medial knife cuts decreased the responsivity to glucose, but less so than the lateral cuts, and did not alter the ingestive response to insulin. Both the medial and lateral knife cuts did not appear to change the rat's responsivity to concentrated blucose solutions. The neuroanatomical and functional nature of the disorder responsible for these effects and its relationship to the hyper-phagia-obesity syndrome are discussed.
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PMID:Effects of hypothalamic knife cuts on the ingestive responses to glucose and insulin. 119

The Obese Zucker rat is a model of genetic obesity characterized by hyperphagia, hyperinsulinemia and other endocrine abnormalities. In order to elucidate pathogenetic mechanisms contributing to disturbed feeding behavior in these animals, the effect of food restriction on three hypothalamic neuropeptides involved in the control of food intake was studied. Eighteen male obese and 18 lean Zucker rats were randomly divided into two groups: half of the animals were food-restricted for 2 weeks, while the other half served as controls and were fed ad libitum. The levels of preproneuropeptide Y (preproNPY), preprocorticotropin releasing factor (preproCRF) and preprosomatostatin (preproSOM) mRNAs were determined using in situ hybridization technique. In addition, plasma insulin and corticosterone concentrations were analyzed. Food restriction significantly increased the expression of preproNPY mRNA in the arcuate nucleus in both Zucker phenotypes, while the expressions of preproCRF mRNA in the paraventricular nucleus (PVN) and preproSOM mRNA in the periventricular nucleus (PeV) were not altered. The expression of preproNPY mRNA was significantly greater in control obese animals compared to control lean animals. Food restriction lowered plasma insulin levels, but did not change plasma corticosterone levels. It is concluded that food restriction specifically activates NPY gene transcription in the arcuate nucleus the response being similar in both Zucker phenotypes. The results suggest that orexigenic NPY plays a role in the adaptation to altered feeding status.
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PMID:Hypothalamic neuropeptide expression after food restriction in Zucker rats: evidence of persistent neuropeptide Y gene activation. 136 27

Neuropeptide Y (NPY) is a major hypothalamic peptide which is implicated in the regulation of energy balance and in the activation of the hypothalamo-pituitary adrenal axis. This study aimed primarily to determine the effects on regional hypothalamic NPY levels, of catabolism and weight loss induced in rats by the synthetic glucocorticoid, dexamethasone, injected daily at a dose of 0.4 mg/kg for 7 days. NPY concentrations were significantly raised in the paraventricular nucleus (PVN) of male Wistar rats (45%, p = 0.009; n = 10) compared with saline-injected controls (n = 10). Body weight (p less than 0.001) and food intake (p less than 0.001) were significantly reduced, plasma insulin concentrations were increased (p less than 0.001), but there was no change in glucose concentrations. Chronic dexamethasone treatment did not cause the marked NPY increases in the arcuate nucleus (ARC) and other hypothalamic regions which have been observed in other catabolic states causing weight loss. One possible explanation is the high insulin levels induced by dexamethasone, which may have prevented compensatory hyperphagia by suppressing an increase in hypothalamic NPYergic activity. We also examined the acute effects of a single dexamethasone injection on regional hypothalamic levels, to determine whether the drug had a direct action separate from that due to sustained weight loss. In the acute study, groups of rats (n = 7) were examined at 4 h after a single injection of dexamethasone or saline. NPY concentrations were significantly increased in the lateral hypothalamic area (LHA), (60%, p = 0.008) when compared with saline-injected controls, but there was no change in body weight or glucose or insulin concentrations during the 4h interval. Altered transport or release of NPY in the lateral hypothalamic area may be a result of acute feedback regulation by glucocorticoids on the hypothalamus.
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PMID:The effect of dexamethasone on neuropeptide Y concentrations in specific hypothalamic regions. 140 50


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