Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of insulin-dependent diabetes mellitus in the BB rat requires the presence of the class II major histocompatibility complex alleles of the RT1u haplotype and a T cell lymphopenia. The lymphopenia gene (lyp) behaves as an autosomal recessive trait that co-segregates with markers of rat chromosome 4. The current study examines two congenic and four recombinant inbred rat strains derived from BB and Buffalo rat strains using markers for simple-sequence length polymorphisms to confirm the linkage of the lymphopenia gene to chromosome 4. In two of these lines the lymphopenia associates with a recombinant haplotype that is BB-like at the D4Mit6 marker and Buffalo-like at D4Mit7 (neuropeptide Y locus) thus placing the lyp locus between these two closely linked markers.
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PMID:Recombinant haplotype bearing the lymphopenia gene of the BB rat. 771 Jul 64

Central administration of neuropeptide Y (NPY) produces a robust feeding response in the rat. It is still unclear how, and in response to what endogenous stimuli NPY is released. We have developed a radioimmunoassay-linked microdialysis procedure for measuring hypothalamic NPY release in both the anaesthetised and freely moving rat. We have used the procedure to show that anaesthesia dramatically decreased NPY release, while a 48 h period of food deprivation significantly increased extracellular NPY concentrations. Streptozotocin-induced diabetic rats also showed increased hypothalamic NPY release compared to controls. These results provide more evidence that NPY may be involved in mediating the hyperphagia associated with starvation and diabetes mellitus. The development of a sensitive microdialysis procedure to measure NPY will allow further detailed investigation of the hypothalamic NPY system.
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PMID:Effect of food deprivation and streptozotocin-induced diabetes on hypothalamic neuropeptide Y release as measured by a radioimmunoassay-linked microdialysis procedure. 780 26

Signals that regulate long-term energy balance have been difficult to identify. Increasingly strong evidence indicates that insulin, acting on the central nervous system in part through its effect on neuropeptide Y (NPY), inhibits food intake. We hypothesized that corticosteroids and insulin might serve as interacting, reciprocal signals for energy balance, acting on energy acquisition, in part through their effects on hypothalamic NPY, as well as on energy stores. Because glucocorticoids also stimulate insulin secretion, their role is normally obscured. Glucocorticoids and insulin were clamped in adrenalectomized rats with steroid replacement and streptozotocin-induced diabetes. Glucocorticoids stimulated and insulin inhibited NPY mRNA and food intake. Glucocorticoids inhibited and insulin increased energy gain as determined by the change in body weight. When adrenalectomized diabetic rats were treated, corticosterone stimulated and insulin inhibited food intake, and, respectively, inhibited and increased overall energy gain. More than 50% of the variance was explained by regression analysis of the two hormones on food intake and body weight. Thus glucocorticoids and insulin are major, antagonistic, long-term regulators of energy balance. The effects of corticosterone and insulin on food intake may be mediated, in part, through regulation of hypothalamic NPY synthesis and secretion.
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PMID:Glucocorticoids and insulin: reciprocal signals for energy balance. 784 Mar 15

To test the hypothesis that diabetic hyperphagia results from insulin deficiency in the brain, diabetic rats (streptozotocin-induced) were given an intracerebroventricular (ICV) infusion of saline or insulin (at a dose that did not affect plasma glucose levels) for 6 days. Food and water intake were significantly increased in diabetic rats, but only food intake was affected by ICV insulin. Diabetic hyperphagia was reduced 58% by ICV insulin compared with ICV saline (P < 0.05) and was accompanied by a 69% increase in diabetes-induced weight loss (P < 0.05). To evaluate whether central nervous system (CNS) insulin deficiency affects expression of neuropeptides involved in food intake, in situ hybridization was done for neuropeptide Y (NPY), which stimulates feeding, in the hypothalamic arcuate nucleus and for cholecystokinin (CCK) and corticotropin-releasing hormone (CRH), which inhibit feeding, in the hypothalamic paraventricular nucleus. In diabetic rats, NPY mRNA hybridization increased 280% (P < 0.05), an effect reduced 40% by ICV insulin (P < 0.05). CCK mRNA hybridization increased 50% in diabetic rats (P < 0.05), a response reduced slightly by ICV insulin (P < 0.05), whereas CRH mRNA hybridization decreased 33% in diabetic rats (P < 0.05) and was unchanged by ICV insulin. The results demonstrate that CNS infusion of insulin to diabetic rats reduces both hyperphagia and overexpression of hypothalamic NPY mRNA. This observation supports the hypothesis that a deficiency of insulin in the brain is an important cause of diabetic hyperphagia and that increased hypothalamic NPY gene expression contributes to this phenomenon.
Diabetes 1995 Feb
PMID:Effect of intracerebroventricular insulin infusion on diabetic hyperphagia and hypothalamic neuropeptide gene expression. 785 32

Neural regulation of islets of Langerhans mediates responses to stress and food ingestion. Transplantation of isolated islets offers hope to patients with insulin dependent diabetes mellitus but denervation of isolated islets may affect the capacity for appropriate metabolic control. Previous examination of the endocrine response to stress in islet autografted dogs revealed differences consistent with loss of neural regulation. Therefore, in the present study, islets grafted in rats were examined for extent and nature of reinnervation. Islets isolated from syngeneic donors were grafted under the kidney capsule of Wistar-Furth rats (n = 7) after 3 wk of streptozotocin induced diabetes. After 4 mo, graft-bearing kidneys were recovered and processed for double immunofluorescence. Antibodies were directed against (a) neuron associated proteins: synapsin (SYN) and L1; (b) neurotransmitters; tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP); and (c) islet hormones: insulin and somatostatin. SYN and L1 immunoreactivities in nerve fibres suggested reinnervation of the grafted islets although fibres were not associated with structures within the transplanted islets as in intact islets. CGRP immunoreactivity was observed in fibres and in a subpopulation of cells within intact islets but only in cells of the grafted islets. VIP, TH, and NPY immunoreactivities were found in nerve fibres of intact islets but only VIP was observed in fibres of grafted islets suggesting an absence of sympathetic reinnervation. In conclusion, transplanted islets of Langerhans become reinnervated but with a distribution and complement of neurotransmitters distinct from intact islets.
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PMID:Reinnervation of isolated islets of Langerhans transplanted beneath the kidney capsule in the rat. 791 58

Obesity is a vast and ever-expanding problem in affluent societies, which we have so far failed to confront. Over 20% of Western European and North American adults are overweight to a degree which may potentially shorten their life expectancy. Obesity has well-known associations with non-insulin-dependent diabetes (NIDDM), hypertension, dyslipidaemia and coronary heart disease, as well as less obvious links with diseases such as osteoarthrosis and various malignancies; it also causes considerable problems through reduced mobility and decreased quality of life. The overall financial burden of obesity is impossible to calculate precisely, but may account for 6-8% of total health-care expenditure in North America [1] (similar estimates probably apply to Western Europe). Obesity is difficult to treat and many patients remain obstinately overweight despite our best efforts. The available options range from behavioural therapy to gastrointestinal surgery and include numerous drugs designed to suppress appetite or increase energy expenditure. As in many other areas of medicine, the length and diversity of this list are reliable signs that effective treatment is still beyond our reach. This article argues that new anti-obesity drugs may emerge from recent advances in understanding the control of energy balance in rodents. The discussion is structured around neuropeptide Y (NPY), a major brain peptide which at present appears to be important in regulating energy balance and seems a promising candidate for therapeutic exploitation.
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PMID:Neuropeptide Y and energy balance: one way ahead for the treatment of obesity? 791 92

Intracerebroventricular injection of neuropeptide Y (NPY) has two effects on energy metabolism in addition to increased feeding: decreased brown fat thermogenesis and increased white fat lipoprotein lipase (LPL) enzymatic activity. We hypothesized that the paraventricular nucleus (PVN) of the hypothalamus is the controlling neural site for these responses. We further hypothesized that NPY stimulation at PVN would reduce gene expression for the critical brown fat thermogenic protein, uncoupling protein (UCP), and increase gene expression for the key white fat storage enzyme, LPL. In the first experiment, three groups of rats received injections every 6 h for 24 h (5 injections total) into the PVN:1) NPY (1 micrograms/1 microliters injection) and ad libitum food; 2) NPY (1 micrograms/1 microliters injection) and food restricted to control intake; 3) saline injection (1 microliter) and ad libitum food. Both NPY-treated groups showed significant reductions (P < 0.05) in brown fat UCP mRNA levels and marked stimulation of LPL mRNA levels relative to controls. In the second experiment, four groups of seven rats had NPY injected into the PVN:0 (vehicle control); 0.1 microgram; 0.5 microgram; and 1 microgram. Injections were made every 6 h for 24 h. There was a dose-related reduction in UCP mRNA produced by the NPY treatment. NPY treatment increased LPL mRNA, but a smooth dosing effect was not evident. The observation that NPY in the PVN can coordinate more than one component of energy metabolism is significant when considered with many reports of responsiveness of NPY activity in the arcuate nucleus-PVN neural circuit to perturbations of energy balance such as fasting and feeding, diabetes, and genetic obesity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptide Y in hypothalamic paraventricular nucleus: a center coordinating energy metabolism. 802 26

Neuropeptides are ubiquitous in the sympathetic system and modulate transmission at the levels of the intermediolateral cell column, sympathetic ganglia, and neuroeffector junctions. Several neuropeptide-containing pathways from the hypothalamus and medulla modulate excitability of preganglionic neurons. Neuropeptides coexist with norepinephrine or acetylcholine in subpopulations of chemically coded, target-specific sympathetic ganglion neurons. Neuropeptide Y is colocalized in adrenergic vasoconstrictor neurons, whereas vasoactive intestinal polypeptide is colocalized in cholinergic sudomotor neurons. Neuropeptide expression is plastic; during development, neurons that switch from a noradrenergic to a cholinergic phenotype increase expression of vasoactive intestinal polypeptide, somatostatin, and substance P. Preganglionic inputs increase neuropeptide Y and inhibit substance P expression. Sympathetic denervation produces sprouting of sensory fibers containing substance P and calcitonin gene-related peptide in target tissues. Neuropeptides from preganglionic fibers (e.g., enkephalin) and primary afferents (e.g., substance P, vasoactive intestinal polypeptide) modulate transmission in sympathetic ganglia. Neuropeptide Y produces vasoconstriction, prejunctional inhibition of norepinephrine release, and postjunctional potentiation of norepinephrine effects. Plasma neuropeptide Y increases during intense sympathoexcitation, hypertension, and pheochromocytoma. Dystrophic neurites containing neuropeptide Y occur in human sympathetic ganglia during aging, diabetes, and dysautonomia. Sympathetic neuropeptides may thus have important clinical implications.
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PMID:Neuropeptides in the sympathetic system: presence, plasticity, modulation, and implications. 802 63

Given that several genetically obese rodents characterized by hyperphagia, hyperinsulinemia, and insulin resistance have increased hypothalamic neuropeptide Y (NPY) mRNA and peptide content, the impact of NPY administered intracerebroventricularly (i.c.v.) for 7 days to normal, awake rats was investigated. NPY produced marked hyperphagia, increased body weight gain, increased basal insulinemia, and, more importantly, a much greater insulin response to meal feeding than that of saline-infused controls. NPY administration also resulted in a pronounced increase in the in vivo insulin-stimulated glucose uptake by adipose tissue but in a marked decrease in uptake by eight different muscle types. Increased insulin responsiveness of the glucose transport process by adipose tissue was accompanied by increases in both GLUT4 mRNA and protein levels. In contrast, the decreased insulin responsiveness of glucose uptake in muscles from NPY-administered rats was not related to GLUT4 expression. We conclude that i.c.v. NPY administration to normal rats produces a hormonal-metabolic situation that is similar to that reported in the dynamic phase of the genetic obesity of the fa/fa strain. Thus, NPY could be of primary importance in the establishment of obesity syndromes with incipient insulin resistance.
Diabetes 1994 Jun
PMID:Intracerebroventricular administration of neuropeptide Y to normal rats has divergent effects on glucose utilization by adipose tissue and skeletal muscle. 819 61

Vanadate treatment can lower glycemia in diabetic rats. This action is generally attributed to vanadate's insulinomimetic properties, but vanadate also inhibits feeding, which could lower blood glucose. We therefore assessed the contribution of hypophagia to vanadate's antihyperglycemic action in a 3-week study of streptozocin-induced (STZ) diabetic rats. Untreated diabetic rats (n = 8) ate 54% more food than nondiabetic control rats (P < 0.001). Diabetic rats given sodium metavanadate (0.5 mg in 0.5 ml of water by gavage twice daily; n = 8) had significantly lower food intakes (P < 0.001) than untreated diabetic rats. In vanadate-treated diabetic rats, blood glucose levels were significantly lower than in untreated diabetic rats (P < 0.001). Untreated diabetic rats pair-fed to the food intake of the vanadate-treated diabetic rats (n = 8) showed virtually identical blood glucose falls (P > 0.05 vs. vanadate-treated diabetic rats). Vanadate treatment did not affect plasma insulin concentrations in diabetic rats. In nondiabetic rats (n = 8), vanadate treatment significantly reduced food intake (P < 0.05) and also lowered plasma insulin concentrations (P < 0.05) without significantly affecting glycemia. To investigate the mechanism of vanadate's hypophagic effect, we also measured regional hypothalamic levels of neuropeptide Y (NPY), a potent central appetite stimulant that is thought to drive hyperphagia in STZ-induced diabetes. Hypothalamic NPY concentrations rise markedly in diabetes and are normalized by insulin replacement. Unlike insulin, vanadate treatment did not normalize regional hypothalamic NPY concentrations in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1994 Jan
PMID:Effects of chronic vanadate administration in the STZ-induced diabetic rat. The antihyperglycemic action of vanadate is attributable entirely to its suppression of feeding. 792 99


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