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)

This study explored some toxicological aspects of vanadyl sulphate (VOSO4) treatment of rats made diabetic with a single intravenous injection of streptozotocin (60 mg/kg). Administered in drinking water (0.25, 0.5, 0.75 or 1 mg of VOSO4, 5H2O ml) VOSO4 treatment partially or totally corrected some of the alterations associated with the diabetic state (hyperglycaemia, polydipsia, polyphagia, high cholesterol and triglycerides levels) and did not produce any changes in various plasma or blood cell parameters which were not previously altered by diabetes. Measurement of vanadium levels indicated that tissues accumulated vanadium in the following order of concentrations: bone greater than kidney greater than spleen greater than liver greater than lung greater than or equal to muscle greater than blood. Histopathological studies did not reveal any difference in liver, stomach, ileum, spleen, heart and lung from control, non-treated diabetic or VOSO4-treated diabetic animals. Kidney of all non-treated diabetic animals showed an epithelial cellular swelling of distal tubules while only 2 of 6 VOSO4-treated diabetic animals showed this alteration. Cellular degeneration of pancreas B-cells was less marked in VOSO4-treated that in non-treated diabetic animals. The study indicates that VOSO4 may be a potential antidiabetic agent.
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PMID:Toxicological aspects of vanadyl sulphate on diabetic rats: effects on vanadium levels and pancreatic B-cell morphology. 225 74

The pharmacokinetics of oral phenobarbitone was studied in 10 clinically healthy adult dogs. The drug was given once daily in tablet form, at a dose of 5 mg kg-1 of body mass. Serial venous blood samples (n = 9) were collected from each dog on Day 1 (the first day of drug dosing), on Day 22, and on Day 24 after continuous dosing. Trough serum concentrations were determined on Day 7, Day 14 and Day 21. The drug was administered to the dogs on an empty stomach, except on Day 24, when it was given with food, in order to assess the influence of food on its absorption. Drug serum concentrations were described by a one-compartmental open model with first order absorption and elimination. An average steady-state trough serum level of phenobarbitone of 52,96 +/- 8.40 mmol l-1 was achieved after 3 weeks of daily dosing. The mean elimination half-lives for Day 1 and Day 22 were 46.3 +/- 11.3 h and 29.3 +/- 4.6 h respectively. The area under the curve for Day 22 was 1,656.17 +/- 186.45 mumol h-1 l-1 and for Day 24 was 1,493.06 +/- 205.4 mumol h-1 l-1. The mean clearance value for Day 22 was 0.0133 +/- 0.0016 l h-1 kg-1. Side effects of polyphagia, polydipsia, sedation and ataxia were commonly observed in the first 2-9 d, but disappeared thereafter. It was concluded that a dose of 5 mg kg-1 would achieve an average serum concentration of 64.59 mumol l-1 in adult dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pharmacokinetics of phenobarbitone in fasting and non-fasting dogs. 228 6

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).
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PMID:Acromegaly in 14 cats. 240 66

The significance of portal venous drainage after whole-pancreas transplantation both for metabolic control and development of diabetic nephropathy was investigated. Streptozotocin-diabetic inbred LEW rats received a duct-ligated pancreas graft with either systemic or portal venous drainage and were followed for up to one year. Normal and untreated diabetic rats (n=18 in each group) served as controls. Irrespective of the route of venous drainage pancreas transplants normalized the diabetic polyuria, polyphagia, and polydipsia. Growth rates and general health did not differ from normal rats. Pancreas transplantation with portal venous drainage furthermore normalized nonfasting blood glucose and peripheral insulin levels, and intravenous glucose tolerance. Pancreas transplantation with systemic venous drainage, however, was associated with peripheral hyperinsulinemia, slightly elevated nonfasting blood glucose levels, and supranormal K-values in intravenous glucose tolerance tests. Though portal venous drainage was associated with better metabolic control than systemic venous drainage, both techniques of pancreas transplantation proved equally effective to prevent the development of diabetic glomerular membrane thickening determined 6 and 12 months posttransplant.
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PMID:Significance of portal venous drainage after whole-organ pancreas transplantation for endocrine graft function and prevention of diabetic nephropathy. 240 87

Quantitative cytophotometry and ocular filar micrometry were used to monitor T-2 toxin induced alterations in chromatin and neuronal nuclear volume in supraoptic-magnocellular neurons of rat hypo-thalami. Thirty male Sprague-Dawley rats (200-220g) were given a single i.p. injection of T-2 toxin (0.5, 0.75, 1.0 and 1.5 X LD50), a trichothecene mycotoxin; rats were decapitated 8 hours post-dosing. After stoichiometric Feulgen-DNA staining of brain sections, scanning-integrating microdensitometry was used to quantify changes in the susceptibility of chromatin to Feulgen acid hydrolysis. Changes in neuronal nuclear volumes were also determined histometrically. Within the magnocellular neurons of the supraoptic nuclei, significant reductions in F-DNA reactivity were observed in the 0.5, 0.75, and 1.0 X LD50 groups (i.e. 3.7%, 4.4% and 2.5%, respectively); however, rats receiving 1.5 X LD50 T-2 toxin showed no difference in F-DNA reactivity compared to controls. In addition, ocular filar micrometry demonstrated increased neuronal nuclear volumes in all groups receiving T-2 toxin, and following an inverse trend to that seen with F-DNA stainability. Additional observations included pronounced polydipsia, polyphagia and horripilation in the experimental groups, independent of the dosages employed; these changes were evident within 1 hour post-injection. It is postulated that the T-2 toxin induced reduction in the susceptibility of chromatin to Feulgen acid hydrolysis and concomitant increases in neuronal nuclear volumes represent an early indication of impaired metabolic activity. Since these neurons are important sites of vasopressin (antidiuretic hormone) synthesis, these data suggest an impaired osmoregulatory ability. The pronounced polydipsia which occurred shortly after intoxication is further evidence of this impairment. Although these findings do not provide insight relating to the mechanism of osmoregulatory disruption, it is evident that an impaired ability to osmoregulate is among the earliest indications of acute T-2 toxin mycotoxicosis.
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PMID:Cytophotometric analysis of T-2 toxin induced alterations in chromatin condensation and neuronal nuclear volume of rat supraoptic-magnocellular neurons. 247 68

Myogenic satellite cells were isolated from nondiabetic and streptozotocin-diabetic rats and studied in vitro. Streptozotocin (STZ) administration produced both hyperglycemia and glucosuria in adult rats when compared to controls. (P less than 0.01), with 12.5% mortality in untreated animals. Insulin therapy diminished blood glucose levels to those found in nondiabetic animals. Only STZ-diabetic rats displayed symptoms of Type I diabetes, including polydipsia, polyuria, and hyperphagia. STZ-treated rats possessed less leg muscle mass and less subcutaneous, intermuscular, and intramuscular fat. Conversely, nondiabetic rats had a greater mean body weight (P less than 0.01) at the end of the experiment than did diabetic rats. Primary cultures of diabetic-derived satellite cells displayed decreased overall ability (P less than 0.01) to fuse to form multinucleated myotubes in vitro than controls. In addition, secondary cultures of diabetic-derived satellite cells achieved maximal fusion one day later than secondary cultures of control-derived cells. Collectively, these data provide preliminary evidence to suggest that untreated insulin-dependent diabetes results in altered fusion characteristics of myogenic satellite cells. Additional studies utilizing satellite cells from diabetic animals will provide valuable definition of the satellite cell involvement in skeletal muscle autophagy which is a symptom of type I diabetes.
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PMID:Satellite cells derived from streptozotocin-diabetic rats display altered fusion parameters in vitro. 252 36

The effects of streptozotocin-induced diabetes on weight gain, bone growth and GH secretion have been studied in conscious chronically cannulated male rats. In addition to the classic diabetic symptoms (hyperphagia, polydipsia, polyuria, glycosuria and hyperglycaemia), the slow body weight gain (0.95 +/- 0.5 compared with 2.63 +/- 0.5 g/day in non-diabetic controls) was associated with a reduction in bone growth (from 162 +/- 9 to 48 +/- 4 microns/day) and a reduced pituitary GH content (from 1.5 +/- 0.2 to 0.6 +/- 0.06 mg/gland). Serial blood sampling during the day or overnight showed that the normal male episodic GH secretory pattern was obliterated in the diabetic animals. The constant osmotic stimulation of hyperglycaemia and high fluid turnover was reflected in a significant reduction in pituitary oxytocin and arginine vasopressin (AVP) stores. Intravenous insulin infusions (67-1340 pmol/h for 4 or 7 days) caused a large initial weight gain (greater than 20 g in 2 days) followed by a slower increase, and stimulated tibial bone growth (to 100 +/- 16 and 126 +/- 8 microns/day after 4 or 7 days respectively). Insulin infusion for 7 days also increased pituitary GH content (to 1 +/- 0.15 mg/gland), and the normal episodic GH secretory pattern returned. Intravenous infusions of insulin which reduced, but did not completely normalize, blood glucose levels, allowed the resumption of growth and pulsatile GH secretion. Continuous infusion of recombinant human insulin-like growth factor-I (hIGF-I) at 1110 pmol/h for 54 h also caused a large initial rise in body weight in diabetic rats (17.1 +/- 1.6 compared with 7.5 +/- 2.8 g in saline-infused controls) due primarily to increased fluid retention. This effect of hIGF-I occurred without any significant changes in pituitary GH, AVP, oxytocin, blood glucose or bone growth over this short-term infusion, nor was there any obvious effect on spontaneous GH secretion, monitored over the entire infusion period. We conclude that the diabetic rat is not a good model to study growth stimulation by short-term insulin or IGF-I treatments because the insulin-like effects of these peptides obscure their specific growth-promoting activities in this model.
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PMID:Growth hormone and growth in diabetic rats: effects of insulin and insulin-like growth factor-I infusions. 268

Twelve plants used for the traditional treatment of diabetes mellitus in northern Europe were studied using normal and streptozotocin diabetic mice to evaluate effects on glucose homeostasis. The plants were administered in the diet (6.25% by weight) and/or as decoctions or infusions in place of drinking water, to coincide with the traditional method of preparation. Treatment for 28 days with preparations of burdock (Arctium lappa), cashew (Anacardium occidentale), dandelion (Taraxacum officinale), elder (Sambucus nigra), fenugreek (Trigonella foenum-graecum), guayusa (Ilex guayusa), hop (Humulus lupulus), nettle (Urtica dioica), cultivated mushroom (Agaricus bisporus), periwinkle (Catharanthus roseus), sage (Salvia officinale), and wild carrot (Daucus carrota) did not affect the parameters of glucose homeostasis examined in normal mice (basal plasma glucose and insulin, glucose tolerance, insulin-induced hypoglycaemia and glycated haemoglobin). After administration of streptozotocin (200 mg/kg) burdock and nettle aggravated the diabetic condition, while cashew, dandelion, elder, fenugreek, hop, periwinkle, sage and wild carrot did not significantly affect the parameters of glucose homeostasis studied (basal glucose and insulin, insulin-induced hypoglycaemia, glycated haemoglobin and pancreatic insulin concentration). Guayusa and mushroom retarded the development of hyperglycaemia in streptozotocin diabetes and reduced the hyperphagia, polydipsia, body weight loss, and glycated haemoglobin. Mushroom also countered the initial reduction in plasma insulin and the reduction in pancreatic insulin concentration, and improved the hypoglycaemic effect of exogenous insulin. These studies suggest the presence of potentially useful antidiabetic agents in guayusa and mushroom.
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PMID:Glycaemic effects of traditional European plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. 274 11

Seven plants and a herbal mixture used for traditional treatment of diabetes were studied in streptozotocin diabetic mice. The treatments were supplied as 6.25% by weight of the diet for 9 days. Consumption of diets containing bearberry (Arctostaphylos uva-ursi), golden seal (Hydrastis canadensis), mistletoe (Viscum album) and tarragon (Artemisia dracunculus) significantly reduced the hyperphagia and polydipsia associated with streptozotocin diabetes, but bayberry (Cinnamomum tamala), meadowsweet (Filipendula ulmaria), senna (Cassia occidentalis) and the herbal mixture did not alter these parameters. Bearberry, mistletoe and tarragon retarded the body weight loss but none of the eight treatments significantly altered plasma glucose or insulin concentrations. These studies suggest that bearberry, golden seal, mistletoe and tarragon may counter some of the symptoms of streptozotocin diabetes without, however, affecting glycemic control.
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PMID:Evaluation of traditional plant treatments for diabetes: studies in streptozotocin diabetic mice. 275 Apr 45

Hepatic clearance and biliary excretion of model substrates for each of four carrier-mediated transport systems were studied in male Sprague-Dawley rats treated 28 days earlier with 45 mg/kg streptozotocin iv to induce uncontrolled insulin-deficient diabetes. Diabetic rats exhibited hyperglycemia (560 mg/dl), polyuria (160 ml/24 hr), polyphagia, polydipsia, and generalized myopathy. The plasma disappearance, biliary excretion, and elimination half-life of the anionic dye phenol red was unchanged in diabetic rats, but total clearance of phenol red was increased. Conjugation of phenol red with glucuronic acid appeared to be increased in diabetic rats, whereas acetylation of procainamide ethobromide was decreased. Plasma elimination and total clearance of cationic procainamide ethobromide, uncharged ouabain, and the bile acid taurocholate were significantly increased in diabetic animals. Biliary excretion of these three compounds was only slightly elevated in the first 15 min after administration and was decreased after 1 hr. Biliary and total systemic clearance were also increased from 2-3-fold for procainamide ethobromide, ouabain, and taurocholate. These changes in clearance are predominantly due to the 2-5-fold increase in steady state volume of distribution. Basal bile flow rates were increased by 62% after the induction of diabetes to 88 microliter/min/kg. Diabetic rats secreted higher levels of bile acids, cholesterol, and phospholipids into bile. These data indicate that long term insulin-dependent diabetes does alter hepatic excretory function.
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PMID:Alterations in biliary excretory function by streptozotocin-induced diabetes. 288 74


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