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)

Dexfenfluramine has been shown to lower blood glucose concentrations independently of its effects in reducing food intake and body weight, in human and animal syndromes of non-insulin dependent diabetes. This study aimed to determine whether dexfenfluramine could also reduce glycaemia in rats with severe insulin-deficient diabetes induced by the beta-cell toxin, streptozotocin (55 mg kg-1). Three weeks after diabetes induction, nine groups (each n = 10) of diabetic and non-diabetic rats underwent oral glucose tolerance tests (1 g kg-1, by gavage). These tests were preceded by 12-18 h of fasting to remove the confounding effects of hyperphagia in diabetic rats, and to stabilize glycaemia. Dexfenfluramine (1.0 mg kg-1), given 2 h before the glucose challenge, significantly reduced basal glycaemia and decreased the post-challenge glycaemic rise (P < 0.01 vs. untreated diabetics). Dexfenfluramine dosages of 2.5 and 5.0 mg kg-1 both further flattened the post-challenge glycaemic profiles (both P < 0.01 vs. untreated diabetics) and achieved levels that did not differ significantly from those in non-diabetics (both P > 0.05). Subsequently, the studies using dexfenfluramine dosages of 2.5 and 5.0 mg kg-1 were repeated to determine whether the drug affected plasma insulin levels 2 h after dosing. In diabetic rats, plasma insulin concentrations were reduced to 10-20% of non-diabetic values, and were not significantly altered by dexfenfluramine. Acute dexfenfluramine administration therefore improves and (at dosages of 2.5 and 5.0 mg kg-1) essentially normalizes glucose tolerance in rats with severe insulin-deficient diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute dexfenfluramine administration normalizes glucose tolerance in rats with insulin-deficient diabetes. 803 52

The adipocyte hormone leptin reduces food intake in normal animals. During uncontrolled type 1 diabetes, plasma leptin levels fall, whereas food intake increases. To test the hypothesis that low leptin levels contribute to diabetic hyperphagia, we investigated the effect on food intake of replacement of leptin at basal plasma concentrations for 7 days in Long-Evans rats with uncontrolled diabetes induced by streptozotocin (STZ). One group of STZ diabetic rats received saline (STZ + Sal) (n = 11), while the other group (STZ + Lep) (n = 15) received a subcutaneous infusion of recombinant rat leptin (100 microg x kg(-1) x day(-1)) via osmotic minipumps. A nondiabetic control group (Con) (n = 11) received saline only. In the STZ + Sal group, plasma leptin levels decreased by 75% (P < 0.05) from 2.4+/-0.5 on the day before STZ/citrate buffer vehicle (Veh) injection (day 0) to 0.6+/-0.2 ng/ml on day 7. In contrast, plasma leptin levels on days 3-7 were comparable to pretreatment values in both the STZ + Lep group (day 0: 2.6+/-0.4 vs. day 7: 2.5+/-0.3 ng/ml, NS) and the Con group (day 0: 3.8+/-0.4 vs. day 7: 2.9+/-1.0 ng/ml, NS). In the STZ + Sal group, daily food intake increased gradually to values 43% above basal by day 7 (day 0: 24+/-2 to day 7: 33+/-3 g, P < 0.05), whereas food intake did not increase in either the STZ + Lep group (day 0: 24+/-1 vs. day 7: 21+/-2 g, NS), or the Con group (day 0: 23+/-1 vs. day 7: 23+/-2 g). Plasma glucose levels exceeded nondiabetic control values (7.7+/-0.2 mmol/l) in both diabetic groups, but were lower in the STZ + Lep group (17.2+/-1.8 mmol/l) than in the STZ + Sal group (24.3+/-1.1 mmol/l, P < 0.05). To determine if sensitivity to leptin-induced anorexia was affected by STZ treatment, a second experiment was performed in which the effect of intracerebroventricular leptin injection (at doses of 0.35, 1.0, or 3.5 microg) on food intake was measured 10 days after STZ or Veh treatment. Leptin suppressed both 4- and 24-h food intake in the two groups to an equal extent at every dose (by 15, 22, and 35%, respectively). These findings support the hypothesis that the effect of uncontrolled diabetes to lower leptin levels contributes to diabetic hyperphagia and that this effect is not due to altered leptin sensitivity.
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PMID:Low plasma leptin levels contribute to diabetic hyperphagia in rats. 1034 16

To understand latent autoimmune diabetes mellitus in adults (LADA), we compared the clinical characteristics, fasting plasma glucose and C-peptide level, genetic frequency of HLA-DQA1, -DQB1 chain in 25 patients with LADA, 57 patients with insulin-dependent diabetes mellitus (IDDM, 21 patients with children-onset IDDM, 36 patients with adult-onset IDDM with ketosis), 38 patients with NIDDM (mild and moderate 30 patients and severe 8) and 42 normal persons. The onset of age was 20-48 years old associated with obvious polyphagia, and weight loss. Body mass index (BMI) was < or = 25 and fasting plasma glucose was > or = 16.5 mmol/L (297 mg/dl). Fasting and 1, 2 hour post prandial C-peptide level showed low and flatter curve (0.4, 0.8 and 0.8 nmol/L respectively). Glutamate decarboxylase (GAD) antibody was positive. HLA-DQ beta chain substitution of aspartate molecule was at position 57 (susceptic gene). LADA could be diagnosed if a patient has the first point and any point of the second to the fourth point. Patients with LADA should take diet, exercises, especially insulin as early as possible in order to control fasting and post prandial plasma glucose, and prevent from further destroy of residue islet B cells and reduce diabetic complications of eye, kidney and nerve.
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PMID:[Clinical characteristics and main diagnostic points of latent autoimmune diabetes mellitus in adults]. 1037 7

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

We report a 43-year-old man who presented diabetic ketoacidosis 1 year after receiving kidney transplantation. He was a recipient of renal transplantation treated with metyl-prednisolone and tacrolimus regimen. The serum level of tacrolimus was 12.4 ng/ml, and he showed hyperphagia before a month of admission. A week before admission, he was aware of polydipsia, polyuria, and general fatigue. He visited our hospital and was found to have severe hyperglycemia (925 mg/dl), significant ketosis and mild metabolic acidosis (pH 7.341), although he had not been diagnosed as diabetes mellitus. He administrated in our hospital, and was treated with insulin for 5 weeks. He was not obese (BMI = 18.2 kg/m(2)) and had no family history of type 2 diabetes. He was finally treated with diet therapy alone. The 24 h urine C-peptide secretion on the third hospital day was low (8.4 microg per day). However, no autoantibodies against pancreatic islets were positive, and his insulin secretion was recovered at discharge suggesting that he was not type 1 diabetes. Although, tacrolimus has been reported to cause or worsen diabetes mellitus, the present case suggests that it could cause severe decrease in insulin secretion which leading to diabetic ketoacidosis in lean subject without previous history of diabetes mellitus.
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PMID:Sudden onset of diabetes with ketoacidosis in a patient treated with FK506/tacrolimus. 1187 16

Patients with type 1 diabetes are identified after the onset of the disease, when beta cell destruction is almost complete. beta cell regeneration from islet cell precursors might reverse this disease, but factors that can induce beta cell neogenesis and replication and prevent a new round of autoimmune destruction remain to be identified. Here we show that expression of IGF-I in beta cells of transgenic mice (in both C57BL/6-SJL and CD-1 genetic backgrounds) counteracts cytotoxicity and insulitis after treatment with multiple low doses of streptozotocin (STZ). STZ-treated nontransgenic mice developed high hyperglycemia and hypoinsulinemia, lost body weight, and died. In contrast, STZ-treated C57BL/6-SJL transgenic mice showed mild hyperglycemia for about 1 month, after which they normalized glycemia and survived. After STZ treatment, all CD-1 mice developed high hyperglycemia, hypoinsulinemia, polydipsia, and polyphagia. However, STZ-treated CD-1 transgenic mice gradually normalized all metabolic parameters and survived. beta cell mass increased in parallel as a result of neogenesis and beta cell replication. Thus, our results indicate that local expression of IGF-I in beta cells regenerates pancreatic islets and counteracts type 1 diabetes, suggesting that IGF-I gene transfer to the pancreas might be a suitable therapy for this disease.
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PMID:Beta cell expression of IGF-I leads to recovery from type 1 diabetes. 1199 4

Maturity-onset diabetes of the young (MODY) is a rare form of juvenile diabetes mellitus, defined by early onset, absence of ketosis, non-insulin-dependent diabetes and autosomal dominant inheritance. Advances in molecular genetic analysis have identified mutations accounting for different MODY subtypes, all of them associated with defects of insulin secretion. We present a case of a nine year-old boy, admitted to our outpatient clinic because of mild and intermittent osmotic symptoms (polyuria, polyphagia and polydipsia) and persistently high values of fasting blood glucose in the last year. He had a family history of diabetes in three consecutive generations compatible with autossomal dominant inheritance. His height was 138.5 cm (90th centile) and his weight was 33.5 Kg (90th centile). General examination was unremarkable, in a prepubertal boy. A standard oral glucose tolerance test was performed. The fasting blood glucose was 118 mg/dl with a two hour value of 160 mg/dl. ICA, IAA and GAD autoantibodies were undetectable. He started on diet therapy, keeping his fasting blood glucose measurements on the upper limits of normal and HbA1c in the normal range. He was diagnosed as having MODY 2 on a clinical basis, as it is not possible to perform molecular analysis of this pathology in Portugal. As MODY is recently thought to account for 2-5% of all cases of type 2 Diabetes Mellitus it is important to consider it as a possible diagnosis in children who present with incidental hyperglycaemia. Molecular genetic testing is very important as it enables us to make a firm diagnosis of MODY, to define a follow up plan and to reassure patients families, once the prognosis is significantly different among the different sub-types of MODY. We emphathize the need of creating national and international reference centres where such testing can be done.
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PMID:[Mature onset diabetes of the young (MODY)]. 1268 Feb 90

Accumulating evidence indicates that ghrelin plays a role in regulating food intake and energy homeostasis. In normal subjects, circulating ghrelin concentrations decrease after meal ingestion and increase progressively before meals. At present, it is not clear whether nutrients suppress the plasma ghrelin concentration directly or indirectly by stimulating insulin secretion. To test the hypothesis that insulin regulates postprandial plasma ghrelin concentrations in humans, we compared the effects of meal ingestion on plasma ghrelin levels in six C-peptide-negative subjects with type 1 diabetes and in six healthy subjects matched for age, sex, and BMI. Diabetic subjects were studied during absence of insulin (insulin withdrawal study), with intravenous infusion of basal insulin (basal insulin study) and subcutaneous administration of a prandial insulin dose (prandial insulin study). Meal intake suppressed plasma ghrelin concentrations (nadir at 105 min) by 32 +/- 4% in normal control subjects, 57 +/- 3% in diabetic patients during the prandial insulin study (P < 0.002 vs. control subjects), and 38 +/- 8% during basal insulin study (P = 0.0016 vs. hyperinsulinemia; P = NS vs. control subjects) but did not have any effect in the insulin withdrawal study (P < 0.001 vs. other studies). In conclusion, 1). insulin is essential for meal-induced plasma ghrelin suppression, 2). basal insulin availability is sufficient for postprandial ghrelin suppression in type 1 diabetic subjects, and 3). lack of meal-induced ghrelin suppression caused by severe insulin deficiency may explain hyperphagia of uncontrolled type 1 diabetic subjects.
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PMID:Insulin is required for prandial ghrelin suppression in humans. 1463 52

Noradrenaline and neuropeptide Y (NPY) in the hypothalamus regulate a number of important endocrine and autonomic functions. Alterations in brain neurotransmitter content have been described in type 1 diabetes but there is little understanding of whether these changes affect neurotransmitter release. This study examined for the first time, region-specific co-release of NPY and noradrenaline from the hypothalamus of male Sprague-Dawley rats treated intravenously with 48 mg/kg streptozotocin (STZ) or vehicle. Five weeks later, the release of endogenous noradrenaline and NPY was monitored by in vitro superfusion of ventral and dorsal hypothalamus slices under basal and potassium-stimulated conditions. STZ-diabetes induced significant increases in basal noradrenaline and NPY overflow from the ventral hypothalamus (P<0.05); only NPY overflow was increased in the dorsal hypothalamus (P<0.05). Noradrenaline overflow increased similarly to potassium depolarisation in vehicle and STZ-diabetic rats, whereas diabetic rats showed a significantly increased NPY overflow response to potassium depolarisation compared to vehicle rats. These region-specific increases in endogenous noradrenaline and NPY overflow from the hypothalamus in diabetes suggest increased neuronal activity at rest and enhanced responses under some conditions. Increased hypothalamic NPY and noradrenaline overflow most likely contributes to diabetic hyperphagia.
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PMID:Increased endogenous noradrenaline and neuropeptide Y release from the hypothalamus of streptozotocin diabetic rats. 1504 28

One of the most common symptoms of diabetes is extreme hunger, but the brain mechanism underlying this hyperphagia is unknown. The endocannabinoid system has emerged as one of the main food intake regulators in the brain. However, the effects of type 1 diabetes on the endocannabinoid system are not completely known. Thus, the aim of the present work is to establish the possible alterations induced by type 1 diabetes on the brain endocannabinoid system in rats. Western blot and immunocytochemistry were used to measure CB1 and phosphorylated CB1 receptor expression in several prosencephalic regions in streptozotocin-induced type 1 diabetic rats. Serum leptin levels were measured by ELISA. CB1 receptor expression was increased in striatum and hypothalamus of diabetic animals, with no changes in other brain areas studied. CB1 receptor phosphorylation was also increased in the same brain areas. Type 1 diabetes induced significant weight loss, and serum leptin levels were severely decreased. These results reinforce the possible role of the CB1 receptor as a pharmacological target for the clinical management of appetite in diabetic patients.
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PMID:Type 1 diabetes alters brain cannabinoid receptor expression and phosphorylation status in rats. 1840 37


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