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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Untreated insulin-deficient diabetes causes hyperphagia and neuroendocrine disturbances that may be partly mediated by increased hypothalamic activity of neuropeptide Y (NPY), a potent central appetite stimulant. The metabolic signal that stimulates hypothalamic NPY is unknown. This study aimed to determine whether insulin deficiency or hyperglycemia was responsible. Regional hypothalamic NPY concentrations were compared in streptozocin-diabetic (STZ-D) rats rendered nearly normoglycemic by either insulin replacement or food restriction. Untreated STZ-D rats were hyperphagic and showed significantly increased (p less than 0.01) hypothalamic NPY concentrations in the arcuate nucleus and lateral hypothalamic area. Once-daily ultralente insulin injections corrected hypoinsulinemia and hyperglycemia, abolished hyperphagia, and normalized NPY concentrations in all hypothalamic regions. By contrast, food restriction effectively lowered glycemia without raising insulin levels. In these underfed diabetic rats, NPY concentrations rose further and were significantly higher than nondiabetic and untreated diabetic levels in most hypothalamic regions. We conclude that insulin deficiency is a major stimulus to hypothalamic NPY in STZ-D, whereas hyperglycemia may exert an inhibitory influence. These findings support the hypothesis that hypothalamic NPY responds to specific metabolic cues and is involved in regulating energy balance and conserving body weight.
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PMID:Insulin deficiency is a specific stimulus to hypothalamic neuropeptide Y: a comparison of the effects of insulin replacement and food restriction in streptozocin-diabetic rats. 143 14

Experimental diabetes adversely affects hypothalamic control of gonadotropin secretion and sex behavior and induces hyperphagia accompanied by severe body weight loss. Neuropeptide-Y (NPY) stimulates pituitary gonadotropin release, inhibits sexual behavior, and stimulates robust feeding in rats by acting at different sites in the hypothalamus. Therefore, we tested the hypothesis that altered hypothalamic NPY neurosecretion may mediate the constellation of effects observed in streptozotocin-induced diabetic (STZ-D) rats. Adult male rats were made diabetic by a single injection of STZ (50 mg/kg). Five months later, in vitro NPY release from the hypothalamic fragment encompassing the medial basal hypothalamus and preoptic area and NPY concentrations in seven hypothalamic sites were assessed. Basal NPY release was not significantly changed after STZ treatment. However, in response to a 30-min pulse of KCl (45 mM), NPY release from the medial basal hypothalamus-preoptic area of STZ-D rats was significantly increased compared to that in age-matched controls. In the STZ-D rats, NPY concentrations in six of the seven microdissected nuclei, including those mediating control of pituitary gonadotropin, sexual, and feeding behaviors, were increased compared to control values. In an additional study similar increments in NPY concentrations in the hypothalamic sites were observed 6 months after STZ treatment. The effects of insulin on NPY levels in microdissected hypothalamic sites in STZ-treated and BB diabetic rats was next assessed. One group of rats was treated with STZ, and the other group of rats was additionally treated with insulin (6 U/kg.day) for 3 months after development of diabetes with STZ. Again, STZ treatment alone, even for 3 months, increased NPY levels in all seven nuclei, including the suprachiasmatic nuclei. Insulin therapy completely prevented the STZ-induced increments in NPY levels in all hypothalamic sites, and the blood glucose level was 233 +/- 22 mg/dl in insulin-treated STZ-D rats and 496 +/- 6 mg/dl in untreated STZ-D rats. Similarly, NPY concentrations in five of the seven nuclei were unchanged in spontaneously diabetic BB rats (blood glucose, 435 +/- 67 mg/dl) maintained on insulin (5-8 U/kg.day). These results demonstrate that STZ-D rats have a widespread increase in NPY levels in hypothalamic sites, and there is an increase in the evoked release of NPY from the hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuropeptide-Y concentration in microdissected hypothalamic regions and in vitro release from the medial basal hypothalamus-preoptic area of streptozotocin-diabetic rats with and without insulin substitution therapy. 213 23

Central and lateral hypothalamic concentrations of 10 regulatory peptides were measured by radioimmunoassay in streptozocin-induced diabetic (STZ-D) and matched control rats between 1 day and 14 wk after diabetes induction. After 2 wk, both central and lateral hypothalamic neuropeptide Y (NPY) concentrations in STZ-D rats were consistently higher than those found in control rats, with significant 30-50% increases at 4 wk in the central hypothalamus, and at 6 and 14 wk in both central and lateral hypothalamus. Immunocytochemical studies in 4- and 6-wk STZ-D animals showed the appearance of intensely NPY-positive swollen cell bodies in the supraoptic nucleus and a subjective increase in NPY staining of medial hypothalamic nerve fibers. Central hypothalamic concentrations of three other peptides were significantly greater in STZ-D animals than those in control animals at single points (neurotensin, 1 day; calcitonin gene-related peptide, 2 wk; neurokinin, 4 wk). Hypothalamic concentrations of the other six peptides examined (bombesin, galanin, neuromedin B, substance P, somatostatin, and vasoactive intestinal peptide) did not differ significantly between STZ-D and control groups at any time. However, galanin immunostaining in the supraoptic and magnocellular paraventricular nuclei was strikingly concentrated in a reduced number of distended cell bodies. Hypothalamic peptide changes in STZ-D could be related to metabolic disturbance, changes in energy and water balance, altered pituitary function, or other factors. Persistently elevated concentrations of NPY, a very potent central stimulant of eating and drinking, may mediate the hyperphagia and polydipsia characteristic of STZ-D.
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PMID:Increased hypothalamic neuropeptide Y concentrations in diabetic rat. 328 97

The initial effect of streptozotocin diabetes is not hyperphagia, but reduced food intake. Diabetic hyperphagia reaches maximum only after many days. Utilization of body fat may account for the delayed appearance of diabetic hyperphagia; this effect may be mediated by plasma fat metabolites. Plasma levels of free fatty acids (FFAs), ketone bodies, and glycerol are greatly elevated following STZ treatment, but return nearly to normal as diabetic hyperphagia appears.
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PMID:Early streptozotocin diabetes and hunger. 657 72

Effects of salt loading by drinking 0.9% NaCl solution on the myocardial performance in nondiabetic and diabetic Wistar rats were studied using the isolated working heart apparatus. Body weight and fluid and food intakes of these animals were monitored. Blood pressure and plasma levels of glucose, insulin, cholesterol, and triglycerides were also measured. Diabetes was induced by intravenous injection of streptozotocin (60 mg/kg). Diabetic rats were found to develop myocardial dysfunction at 8 weeks after STZ injection, accompanied by significant increases in food and fluid intakes, slowed body weight gain, hyperglycemia, hypoinsulinemia, and hyperlipidemia but without significant changes in blood pressure. Salt loading did not cause significant changes in any of the parameters studied in nondiabetic rats. However, in streptozotocin-diabetic rats given saline to drink, the impaired myocardial function was significantly improved and was associated with a significant reduction in hyperphagia and hyperlipidemia. Plasma glucose levels significantly decreased at weeks 1-3 but increased to the levels of untreated diabetic animals at weeks 4-7. There was an increase in fluid intake, but neither blood pressure nor plasma insulin levels were significantly affected. It is suggested that the improvements in cardiac function and hyperlipidemia in diabetic rats by salt loading may be related to each other; however, the mechanisms for these effects are not clear but are unlikely to be due to changes in glycemic control.
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PMID:Improvement in cardiac function in streptozotocin-diabetic rats by salt loading. 776 68

In this paper, the experimental diabetic rats induced by streptozotocin (STZ, i.p. 50 mg/kg) were divided into three groups, electro-acupuncture (EA group, n = 8), transcutaneous electric nerve stimulation (TENS group, n = 8), at bilateral Shenshu and Zusanli points for 20 minutes once every 2-3 days for five weeks, and without any treatment (DM group, n = 6) respectively. As compared with the DM group, the increased plasma glucose levels was lowered significantly in EA group (P < 0.05) and slightly in TENS group (P > 0.05) by the end of the sixth week. And the symtoms of polyphagia, polydipsia and polyuria were attenuated in EA group. The motor nerve conduction velocity slowing was prevented or corrected after a course of four and six weeks treatment in EA and TENS group respectively. In the DM and TENS groups the pain threshold was lowered at 6-20 days after injection of STZ, but elevated in EA group, their differences were of significance (P < 0.05). In general, the efficiency of EA treatment on experimental diabetes and its neuropathy was better than that of TENS therapy.
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PMID:[Effect of electro-acupuncture and transcutaneous electric nerve stimulation on experimental diabetes and its neuropathy]. 938 43

We have evaluated the suitability of different rat models for the study of effects of antihypertensives on cardiovascular and metabolic complications of diabetes mellitus and hypertension. IDDM was induced in Wistar and spontaneously hypertensive (SH) rats by single tail vein injection of STZ (45 mg/kg, i.v.). Neonatal STZ-diabetes (nSTZ) was induced by administering STZ, 70 mg/kg (i.p.) to 5 day old Wistar rat pups. DOCA-hypertension was induced in Wistar and STZ-diabetic rats using deoxycorticosterone acetate (DOCA, 5 mg/kg, s.c.) and NaCl (2%) in drinking water. Intravenous injection of STZ produced cardinal signs of diabetes mellitus including hyperglycemia, loss of body weight, polyphagia and polydipsia. STZ-diabetic rats also showed hyperlipidemia and hypoinsulinemia. STZ-treated rats developed hypertension and bradycardia. nSTZ rats were found to have mild hyperglycemia and were hypertensive and hyperinsulinemic. The OGTT and ITT revealed that nSTZ rats are insulin resistant. SH rats were also found to be hyperinsulinemic and hypertensive. Although, these rats were found to be insulin resistant, they did not demonstrate hyperglycemia. DOCA-treated STZ-diabetic rats were found to have milder hyperglycemia when compared to STZ-diabetic rats not treated with DOCA. Although, DOCA treatment was not found to alter serum levels of glucose and insulin, results of OGTT revealed enhanced glucose disposal in DOCA-treated Wistar rats, suggesting that DOCA probably produces some effect on glucose homeostasis in rats. The present data also suggest that STZ-diabetic rat may be considered a suitable model for IDDM. On the other hand, nSTZ and SH rats were hyperinsulinemic and insulin resistant and may be used as models to study insulin sensitivity. DOCA-hypertensive rat may not be a suitable model for studying the effects of various drug interventions on glucose homeostasis and insulin sensitivity as DOCA itself appears to influence these factors.
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PMID:Comparative evaluation of different rat models with co-existing diabetes-mellitus and hypertension. 1084 25

In an attempt to elucidate the effect of vanadium compounds on the gene expression of neuropeptide Y (NPY), vanadyl sulfate (VOSO4) was orally administrated at the dose of 1 mg/kg body weight into streptozotocin-induced diabetic rats (STZ-diabetic rats) three times daily for 1 week. We found a marked lowering of plasma glucose with a significant decrease of food and water intake in these STZ-diabetic rats treated with VOSO4, although the weight gain was unaffected. The increase of hypothalamic NPY, both the mRNA level and peptide concentration, in STZ-diabetic rats was also reduced by this oral treatment of VOSO4. However, similar treatment of VOSO4 in normal rats failed to modify the feeding behavior and hypothalamic NPY gene expression. These data suggest that decrease of hypothalamic NPY gene expression by VOSO4 is related to the recovery of hyperphagia in diabetic rats lacking insulin.
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PMID:Decrease of hypothalamic neuropeptide Y gene expression by vanadyl sulfate in streptozotocin-induced diabetic rats. 1129

Plasma levels of the orexigenic hormone, ghrelin, decrease rapidly on nutrient ingestion and yet are paradoxically elevated in rats with hyperphagia induced by streptozotocin-induced diabetes (STZ-DM). In the current work, we investigated the mechanisms underlying the relationships among uncontrolled diabetes, food intake, and plasma ghrelin concentrations in an effort to clarify whether increased ghrelin signaling contributes to diabetic hyperphagia. Whereas food intake did not increase until d 3 after STZ administration, plasma ghrelin levels were increased by more than 2-fold (P < 0.05) on d 1. As hyperphagia developed, however, plasma ghrelin levels declined steadily. Because this reduction of plasma ghrelin levels was reversed by matching food intake of STZ-DM rats to that of nondiabetic controls, our results demonstrated that the effect of uncontrolled diabetes to increase plasma ghrelin levels is partially offset by hyperphagic feeding. In addition, we found that although intragastric nutrient infusion rapidly and comparably decreased plasma ghrelin levels in both groups (by 46-49%; P < 0.05), this effect was short lived in STZ-DM rats relative to nondiabetic controls (60 min vs. 120 min; P < 0.05). We further demonstrated that in rats with STZ-DM, food intake increased by 357% (P < 0.05) in response to intracerebroventricular administration of ghrelin at a dose that was subthreshold for feeding effects in nondiabetic controls. Collectively, these findings demonstrate that uncontrolled diabetes increases both circulating ghrelin levels and behavioral sensitivity to ghrelin. Although plasma ghrelin levels fall in response to hyperphagic feeding, these findings support the hypothesis that increased ghrelin signaling contributes to the pathogenesis of diabetic hyperphagia.
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PMID:Effect of uncontrolled diabetes on plasma ghrelin concentrations and ghrelin-induced feeding. 1525 89

We have evaluated the influence of oligofructose (OFS), a fermentable dietary fibre, on glucose homeostasis, insulin production and intestinal glucagon-like peptide-1 (GLP-1) in streptozotocin-treated diabetic rats. Male Wistar rats received either i.v. streptozotocin (STZ; 40 mg/kg) or vehicle (CT); one week later, they were fed for 6 weeks with either the standard diet (STZ-CT), or with a diet containing 10% oligofructose (STZ-OFS); both diets were available ad libitum. In a second set of experiments (duration 4 weeks), a supplemental group of food-restricted rats (STZ-Res) receiving a similar intake as CT rats, was added. OFS improved glucose tolerance and reduced food intake as compared with STZ-CT rats in both the post-prandial state and after an oral glucose tolerance test. After 6 weeks, portal and pancreatic insulin concentrations were doubled in STZ-OFS rats. Food restriction improved these parameters when compared with STZ-CT rats, but to a lesser extent than in the STZ-OFS group. We have shown that OFS treatment increased portal and colonic GLP-1(7-36) amide levels and doubled colonic proglucagon and prohormone convertase 1 mRNA levels; both OFS and food restriction lowered ileal GLP-1(7-36) amide levels as compared with levels in STZ-CT rats. We propose that OFS, through its fermentation in the colon, promotes the expression and secretion of colonic peptides, namely GLP-1(7-36) amide, with beneficial consequences on glycaemia, insulin secretion and hyperphagia in diabetic rats.
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PMID:Involvement of endogenous glucagon-like peptide-1(7-36) amide on glycaemia-lowering effect of oligofructose in streptozotocin-treated rats. 1593 Jan 72


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