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PubMed1987

Selected physical and biochemical parameters in the streptozotocin-treated guinea pig: insights into the diabetic guinea pig model.

Since evidence suggests that ascorbic acid deficits may provoke certain diabetic complications, it becomes necessary to develop a diabetic animal model which, like man, is unable to synthesize this vitamin. To this end, the present study monitored the diabetogenic effects of streptozotocin (STZ, 150 mg/kg) in the male guinea pig, a species rarely used in diabetes research. Over a 3-week period, body weight and relative food intake were lower in the STZ group compared to controls. The mean daily water intake and urine volume of the STZ group after 1 week were 175 and 270% of their initial pretreatment values, respectively, while control values were unchanged. The STZ group also exhibited a persistent glycosuria throughout the study. At the end of 3 weeks, aldehyde fuchsin staining of pancreatic beta cell granules (an index of stored insulin) was 58% lower in the STZ group compared to controls. Plasma C-peptide (indicator of insulin secretion) was expressed in human equivalents (mean +/- SEM). C-peptide was reduced in the STZ group (103 +/- 65 pg/ml) compared to controls (549 +/- 96 pg/ml); however, no change in plasma glucose was observed. Plasma ascorbic acid levels also were lower for STZ animals (150 +/- 26 micrograms%) versus controls (410 +/- 28 micrograms%). This study 1) demonstrates a diabetic syndrome in the STZ-treated guinea pig based on a reduced growth rate, beta cell dysfunction, polydipsia, polyuria and glycosuria, and 2) suggests the usefulness of this diabetic model in studies of pathologic mechanisms influenced by ascorbic acid.

Animals↗

PubMed1989

Satellite cells derived from streptozotocin-diabetic rats display altered fusion parameters in vitro.

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.

Animals↗

PubMed1991

Beneficial effects of dietary acarbose in the streptozotocin-induced diabetic rat.

Diabetes is characterized by hyperphagia, polydipsia, polyuria, and elevations in blood and urinary glucose. It has also been documented that beta-adrenergic responsiveness is reduced in diabetes. The intestinal glucosidase inhibitor, acarbose (BAY G 5421), decreases postprandial glycemia by delaying carbohydrate absorption. The purpose of this study was to evaluate the effects of chronic acarbose treatment (20 and 40 mg/100 g of diet) on the metabolic and adrenergic parameters altered in streptozotocin (STZ) (50 mg/kg, intravenously [IV] )-induced diabetes. Metabolic parameters were measured daily for 8 weeks. Diabetic rats were hyperphagic, polydipsic, and polyuric within 1 week of STZ treatment. Acarbose treatment did not consistently effect the food intake but did reduce water intake, urinary output, blood glucose, and the urinary loss of glucose associated with STZ-induced diabetes. Adrenergic responses were assessed by monitoring the increase in tail skin temperature (TST) associated with administration of isoproterenol. Diabetic rats were less responsive than controls and acarbose treatment restored responses toward that of the controls. Additionally, 3H-NE release from the tail artery was elevated in the diabetic rat and restored to normal in the acarbose-treated animals. Collectively these data suggest that acarbose treatment is effective in reducing the severity of metabolic and autonomic complications associated with STZ-induced diabetes.

Acarbose↗

PubMed1991

Early indicators of bladder carcinogenesis produced by non-genotoxic agents.

There are several early indicators of non-genotoxic bladder tumorigenicity. The non-invasive indications are polydipsia, diuresis, changes in urine pH and urinary cation concentrations, especially Na and Ca. The indicators requiring invasive techniques are increased bladder weight and increased cell replication assessed by DNA labeling or histologically as epithelial hyperplasia. SEM has been used to characterize bladder surface changes, and a reduction of bladder tissue Ca has been implicated in one mechanism leading to bladder cancer. Wherever multiple species have been tested, the non-genotoxic bladder carcinogens have induced bladder responses only in rats. This is true whether the criterion was complete carcinogenesis, promotion or short-term indicators. It is also evident that the response can vary greatly within rat strains and is dependent upon the diet being fed. These variables make the relevance of the results obtained in the rat bladder of questionable significance to man. In relation to chronic studies it is clear that as the male rat ages it loses the capacity to concentrate urine, probably because of the endemic, age-progressive loss of functional renal tissue. It is also clear that the bladder grows to accommodate the increase in urine output. Thus it is likely that any agent or treatment that causes bladder damage may be associated with increased neoplasia expression in aged male rats. No other species shows the degree of spontaneous nephrosis seen in the male rat, a condition which is both rat strain- and diet-dependent. Finally, it should be recognized that while there are some early indicators of bladder tumorigenesis that can be useful as warning signs, each compound is likely to yield unique responses when its mechanism is studied in detail. To facilitate discussion of the parameters that have been identified as early indicators of bladder tumorigenesis associated with non-genotoxic agents, the proposed mechanisms of cancer development, the information which led to these proposals and a critique of the mechanisms have been presented.

Animals↗

PubMed1975

Dental fluorosis associated with hereditary diabetes insipidus.

Among the characteristics of hereditary pituitary diabetes insipidus are polydipsia and polyuria from early infancy. Drinking of large amounts of water, even with lower than accepted fluoride content, can produce fluorosis of the teeth. A mother and her four children affected by this disorder presented different degrees of fluorosis directly related to the stage at which hormonal therapy was introduced.

Adolescent↗

PubMed1975

Renal deficiency associated with diabetes insipidus in the SWR/J mouse.

The age-dependent polydipsia and polyuria observed in SWR/J mice was found to be caused by relative inability of the kidneys to respond to antidiuretic hormone (ADH), resulting in a concentrating defect, which persisted even following Pitressin injection or water deprivation. Posterior pituitaries contained large amounts of ADH, which was also found in the urine and increased in output following water deprivation, indicating normal, or above normal synthesis and release of ADH. Kidneys of polydipsic SWR/J mice weighed more than those of normal strains and sometimes contained a lesion in the medullary area. No clear relationship was found between the size of the lesion and water intake.

Animals↗

PubMed1979

Concurrent drinking by pigeons on fixed-interval reinforcement schedules.

Three experienced pigeons were exposed to at least ten consecutive 100-min sessions on each of three food-reinforced fixed-interval (FI) schedules: FI 50-sec, FI 100-sec and FI 200-sec. Water was freely available. Drinking was largely confined to the first third of each fixed interval, and the mean sessional water intake was directly related to the food-reinforcement rate for each animal. The animals drank very quickly, i.e., 3--4 ml/sec, but the drinking bouts were brief, i.e., 0.8--1.4 sec, and infrequent, i.e., 2--5/hr. The parameters describing concurrent drinking in the pigeon are strikingly different from those describing rats' drinking under similar reinforcement schedules, which may contribute to the difficulty in demonstrating schedule-induced polydipsia in the pigeon.

Animals↗

PubMed1990

Dynamics of plasma catecholamine and corticosterone concentrations during reinforced and extinguished operant behavior in rats.

Plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) concentrations were determined simultaneously in permanently heart-cannulated rats before and during the performance of reinforced and nonreinforced (extinguished) operant behavior. Shortly before the experimental food-reinforced (VI 15-sec schedule) lever-pressing task, anticipatory elevations of plasma NA and CS contents were observed. During reinforced lever responding plasma NA increased, A did not change and CS declined. Extinction was associated with a transient increase in A, decreasing NA and elevated CS concentrations. In addition, a relationship was found between individual lever-pressing rate, neurosympathetic and adrenomedullary reactivity and the degree of schedule-induced polydipsia. The results indicate that presence and absence of expected behavioral consequences (controllability and loss of control, respectively) are attended by selective, but highly dissociated patterns of neurosympathetic, adrenomedullary and adrenocortical output. Collectively, the findings reinforce the concept that distinctive emotional and/or motivational states are associated with different patterns of neuroendocrine responses. The reactivity of the sympathoadrenomedullary component is heavily dependent upon a rat's individual behavioral strategy.

Adrenal Medulla↗

PubMed1992

Food granules elicit heavy drinking in polydipsic rats independently of meal duration.

Excessive drinking, in rats made polydipsic on intermittent delivery of food pellets, is inversely related to the time the rat spends with its head in the feeder, early in the interfood interval. In a sensitization model, this explains why food textures that induce more oral activity, e.g., powder, do not elicit drinking. This hypothesis was examined by coding the behavior of polydipsic rats and varying the duration of the meal delivered in each interval, while holding texture constant. Polydipsic rats were presented with pellets, food granules, or food powder. The food granules were dispensed over periods lasting 1, 14, 21, and 28 s. All food deliveries were of the same mass. The food was delivered periodically at 60-s intervals in each condition. The 14 rats in the experiment served as their own controls by experiencing every condition. The food granule conditions induced the expected increases in feeding early in the interval. However, instead of progressively reducing drinking, the excessive drinking simply occurred later in the interval. By contrast, the powder condition resulted in the immediate elimination of polydipsia. The results suggest that food texture elicits excessive drinking independently of temporal factors and that elicitation of the sensitized drinking response must depend on other factors.

Animals↗

PubMed1993

Circadian rhythms of food and water intake and urine excretion in diabetic rats.

The light/dark (L/D) rhythms of food and water intake and urine output were studied in normal and diabetic rats for 7 consecutive days at 4-h intervals. The control rats showed the highest values of these parameters during the dark phase (83.68% food, 68.71% water, and 67.44% urine). The diabetic rats also maintained this nocturnal predominance, although the values were less marked (59.55% food, 55% water, and 56% urine). A circadian rhythm of food (phi = 3.31 h) and water (phi = 3.54 h) intake as well as of the volume of urine excreted (phi = 1.10) was detected in the control animals. The diabetic rats, inspite of presenting polyphagia, maintain the circadian rhythm of food intake, whereas a loss of the normal circadian variation of drinking intake was observed as well as the absence of circadian rhythm in urinary excretion. It was concluded that in streptozotocin-diabetic rats we have observed a loss of the normal patterns of water intake and urinary excretion, perhaps masked by the polydipsia and polyuria, whereas the circadian rhythm of food intake remains.

Animals↗

PubMed1993

Effects of phenylpropanolamine on regulatory and nonregulatory ingestion in adult rats.

This experiment examined the effects of phenylpropanolamine (0.0, 5.0, 10.0, 20.0 mg/kg PPA) on regulatory (RG) and nonregulatory (NRG) eating and drinking in rats using a within-subjects design. Administration of PPA produced dose-dependent reductions in eating in animals deprived to 80-85% of baseline weight, and reduced drinking after 23.5-h of water deprivation. Nonregulatory eating, elicited by tail pinch in nondeprived animals, was similarly inhibited. Nonregulatory drinking was elicited in the schedule-induced polydipsia (SIP) paradigm. Water consumption, locomotion, licking, lick efficiency (licks/ml water), and entries into the food magazine were simultaneously measured. At the lowest dose, only locomotion was significantly reduced. At 10.0 mg/kg, lick efficiency and entries into the food magazine were also significantly reduced, while all measured behaviors, including licking and water consumption, were decreased by the highest dose of PPA. The reduction in lick efficiency suggested a PPA-induced motor impairment in the capacity for licking. Considered together, these results indicated that the observed decreases in regulatory and nonregulatory eating and drinking could be at least partially accounted for by the drug's effects on behaviors contributing to ingestion, as well as apparent motor impairments in ingestive behavior at higher doses.

Animals↗

PubMed1994

The abnormal quinine drinking aversion in the Brattleboro rat with diabetes insipidus is reversed by the vasopressin agonist DDAVP: a possible role for vasopressin in the motivation to drink.

The Brattleboro rat with hypothalamic diabetes insipidus (BDI) has an abnormal aversion to drinking quinine-adulterated water compared with normal rats of the parent Long Evans (LE) strain. This BDI animal tolerates marked hypovolemia and decreased body weight in preference to drinking the quinine-adulterated fluid, indicative of a reduced motivation to drink. Acute or chronic treatment of BDI rats with desamino-8D arginine vasopressin (DDAVP) restored to normal their drinking response to quinine solution. Partial restoration of fluid turnover in BDI rats with hydrochlorothiazide, which has an antidiuretic effect in diabetes insipidus (when vasopressin is absent), failed to abolish the abnormal drinking response to quinine-adulterated solution in 8 out of 12 animals. In contrast, induction of diabetes mellitus in LE rats, which resulted in a marked polydipsia and polyuria even though vasopressin was still present, did not impair the drinking response to quinine solutions. These results suggest that the abnormal drinking response to quinine-adulterated fluid in BDI rats is reversed by treatment with the vasopressin V2-receptor agonist DDAVP but is unlikely to be a consequence of the restoration of fluid turnover to normal levels by a renal action. A possible central action involving vasopressin and the motivation to drink is discussed.

Animals↗

PubMed1995

An analysis of excessive running in the development of activity anorexia.

Food restriction combined with activity wheel access produces activity anorexia: a combination of excessive running, reduced food intake and rapid weight loss. Temporal distributions of running in activity anorexia were examined in a reversal design with one of 2 x 2 x 2 factorial combinations (pelleted-vs-powdered food x deprivation x wheel access) as the treatment condition. Wheel revolutions were recorded in 30 min intervals; body weights, food and water intakes were measured daily. Only wheel access combined with food deprivation reliably produced activity anorexia. Excessive running occurred in the absence of schedule-induced polydipsia, was unaffected by food form, and showed distributional characteristics of facultative behavior. These results are inconsistent with schedule-induced behavior explanations. Running distributions appeared consistent with chronobiological models with light/dark onset and feeding serving as zeitgebers.

Animals↗

PubMed1986

Diurnal patterns in homecage behavior of rats after acute exposure to triethyltin.

Diurnal patterns of eating, drinking, locomotor activity, and rearing in male Fischer-344 rats were examined for 11 days after a single oral dose of triethyltin bromide (TET) at 0, 1.5, 3, or 5 mg/kg. The 5 mg/kg group exhibited a time-related drop in food consumption and body weight until 3 of 10 rats were sacrificed moribund 11 days after dosing. Doses of 1.5 and 3 mg/kg TET did not reduce body weight or consumption of food and water. In contrast, food consumption was significantly increased 7 and 11 days after 3 mg/kg TET, and diurnal patterns of eating and drinking were disrupted 7 days after 3 and 5 mg/kg TET. A phase shift in licking patterns was induced by the high dose. Unlike trimethyltin (TMT), TET did not affect efficiency of eating. Diurnal patterns of both horizontal and vertical activity were disrupted at all dose levels on Day 2 after dosing; by 16 days after dosing, recovery was evident in all rats including those surviving 5 mg/kg TET. These results show that a near-lethal dose of TET produced a reversible syndrome of hypoactivity, aphagia, and weight loss similar to that seen after acute TMT; in the absence of the above signs, diurnal patterns of behavior revealed effects of TET at doses as low as 1.5 mg/kg; the magnitude of the effect depended on the time of day at which the response was measured; and TET did not produce the same effects on ingestive behaviors (polydipsia and reduced feeding efficiency) that were previously observed after acute TMT.

Animals↗

PubMed1986

The progression of adriamycin-induced nephrotic syndrome in rats and the effect of captopril.

The progression of adriamycin-induced nephrotic syndrome in rats was studied over a 3-month period. The effect of an angiotensin-converting enzyme inhibitor, captopril, on this model of renal disease, was also studied. Two weeks following a single iv injection of adriamycin, rats were divided into two treatment groups: one received a daily po dose of captopril and the other received a placebo. Measurements of renal function were performed at 4, 8, and 11 weeks following the initiation of therapy. Necropsies and light microscopic evaluation of the kidneys were performed at the end of the treatment period. Functional and morphologic alterations in both groups of rats were compared to each other and to normal age/weight-matched control rats studied over the same time period. At 13 weeks following the administration of adriamycin, both treatment groups had significant renal dysfunction when compared to normal controls. In addition to severe proteinuria, rats receiving adriamycin exhibited polyuria, polydipsia, increased plasma urea nitrogen and plasma creatinine, and decreased endogenous creatinine clearance. They had severe generalized kidney lesions characterized by tubular dilation and atrophy, cast formation, interstitial fibrosis and lymphocytic infiltration, and focal, global glomerulosclerosis. The histopathologic ranking of the kidneys was correlated with some antemortem laboratory parameters but not with the degree of proteinuria. Captopril had no ameliorating effects on the progression of renal disease. Certain findings indicate that captopril may actually have promoted the deterioration of renal function. We conclude that adriamycin-induced nephrotic syndrome in the rat is a progressive disease resulting in generalized renal dysfunction, and that captopril, at the dose given in this experiment, is unable to slow the progression of the disease.

Animals↗

PubMed1991

Crisis in sickle cell trait.

A 34-year-old black male with hemoglobin AS was admitted for renal failure, polydipsia, hypertension, schizophrenia, mental confusion, and visual hallucinations. Abnormal electrolytes were corrected by dialysis, but blood specimens were reported as hemolyzed with hyperkalemia. Peaked T waves on electrocardiographic analysis were followed by cardiac arrest. An autopsy revealed sickled cells in the visual cortex and other symptomatic organs, but normal erythrocytes in most of the vascular tree. These findings suggest true progressive sickle cell crisis in a hemoglobin AS patient.

Adult↗

PubMed1977

Some current aspects of environmental fluoride.

This review presents a Total Environment evaluation of current inorganic fluoride intake by human populations. Inorganic fluoride is a persistant bioaccumulator, and the ever-increasing use (and release) of fluoride compounds in the environment should be of long-term concern in population sub-groups who are most susceptible, and therefore, most "at risk". One of these sub-groups consists of people with impaired kidney function, including subjects with nephorphatic diabetes. The diabetes factor is of particular relevance, not only because the incidence of diabetes has increased by 6%/yr during the period 1965-1975, but also because subjects with nephropathic diabetes can exhibit a polydipsia-polyurea syndrome that results in increased intake of fluoride, along with greater-than-normal retention of a given fluoride dosage. People with inadequate dietary intakes (particularly of Ca and/or Vitamin C) are also likely to be more "at risk" as a consequence of low-dose long-term fluoride ingestion. Evidence is presented, showing that there has been an escalation in dialy fluoride intake via the total human food-and-beverage chain, with the likelihood that this escalation will continue in the future. Recent observations, relating to an increasing incidence of chronic fluoride intoxication among humans, is also emphasized.

Ascorbic Acid Deficiency↗

PubMedDate not supplied

Pattern of daily blood ethanol elevation and the development of physical dependence.

Schedule-induced ethanol polydipsia regimens were used which produced either one or two daily peaks in blood ethanol levels. After 3 months on these regimens, rats were withdrawn from ethanol and tested for the presence of abstinence signs. No evidence of physical dependence was found, a result which contrasted with the previous finding of a severe withdrawal syndrome when blood ethanol was maintained at a more continuously elevated level prior to withdrawal. It was concluded that, as in the case of barbiturates, the development of physical dependence on ethanol requires more than an episodic peaking of the blood ethanol level once or twice per day.

Alcohol Drinking↗