Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the rat, the glucagon-like peptide 1 (GLP-1)(7-36) amide inhibits neurones in the central nervous system responsible for food and water intake. GLP-1-induced inhibition of food intake may involve the hypothalamic arcuate nucleus, whereas rostral sensory circumventricular organs may be responsible for the inhibitory action of GLP-1 on drinking. To further investigate the role of these blood-brain-barrier-free areas in GLP-1-induced inhibition of ingestive behavior, neonatal Wistar rats were subjected to monosodium glutamate (MSG) treatment, which causes extensive damage to the arcuate nucleus as well as to parts of the sensory circumventricular organs. The inhibitory effect of GLP-1 on feeding induced by food deprivation was completely abolished in MSG-lesioned rats. This effect was not due to either a loss of sensitivity to anorectic agents or a loss of taste aversion because MSG-treated animals displayed normal anorectic responses to central administration of corticotropin-releasing factor and normal aversive responses to peripheral administration of both lithium chloride and D-amphetamine. In non-lesioned rats, neuropeptide Y (NPY)-induced feeding was significantly reduced by concomitant GLP-1 administration. In contrast, GLP-1 had no effect on NPY-induced feeding in MSG-lesioned rats, suggesting that the GLP-1 receptors that mediate inhibition of feeding are localized upstream to the NPY-sensitive neurones inducing feeding behavior. The inhibitory effect of GLP-1 on water intake was tested using an ANG II-elicited drinking paradigm. Central administration of GLP-1 inhibited ANG II drinking in both MSG-treated rats and their nontreated littermates. In contrast, peripheral administration of GLP-1 did not inhibit ANG II-induced drinking behavior in MSG-treated rats. Thus it is evident that centrally acting GLP-1 modulates feeding and drinking behavior via neurones sensitive to MSG lesioning in the arcuate nucleus and circumventricular organs, respectively.
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PMID:Glucagon-like peptide 1(7-36) amide's central inhibition of feeding and peripheral inhibition of drinking are abolished by neonatal monosodium glutamate treatment. 956 83

A new dimension to the regulation of energy balance has come from the identification of the ob (obese) gene and its protein product, leptin. Leptin is produced primarily in white adipose tissue, but synthesis also occurs in brown fat and the placenta. Several physiological functions have been described for leptin the inhibition of food intake, the stimulation/maintenance of energy expenditure, as a signal of energy reserves to the reproductive system, and as a factor in haematopoiesis. The production of leptin by white fat is influenced by a number of factors, including insulin and glucocorticoids (which are stimulatory), and fasting, cold exposure and beta-adrenoceptor agonists (which are inhibitory). A key role in the regulation of leptin production is envisaged for the sympathetic nervous system, operating through beta 3-adrenoceptors. The leptin receptor gene is expressed in a wide range of tissues, and several splice variants are evident. A long form variant (Ob-Rb) with an intracellular signalling domain is found particularly in the hypothalamus. Leptin exerts its central effects through neuropeptide Y, and through the glucagon-like peptide-1 and melanocortin systems, but it may also interact with other neuroendocrine pathways. The role and function of the leptin system in agricultural animals has not been established, but it offers a potential new target for the manipulation of body fat.
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PMID:Hormonal and neuroendocrine regulation of energy balance--the role of leptin. 967 15

Pituitary adenylate cyclase activating polypeptides (PACAP27 and PACAP38) are members of the VIP/secretin/glucagon family of peptides and have diverse neuroregulatory effects in sympathoadrenal cell development and function. PACAP peptides regulate rat superior cervical ganglion (SCG) neuron catecholamine and neuropeptide Y content and secretion, and promote sympathoneuroblast survival through activation of specific PACAP1 receptor isoforms. In examining the potential sources of PACAP regulating the SCG, PACAP expression was identified in rat preganglionic neurons in the intermediolateral cell column (IML) of the thoracic spinal cord which provide primary afferent projections to this sympathetic ganglion. Thoracic spinal cord segments (T1-4) contained approximately 17 pmol PACAP38 immunoreactivity/g tissue wet weight. Reverse-transcription polymerase chain reaction of cDNA from microdissected thoracic spinal cord using primers specific for rat neuronal proPACAP identified proPACAP mRNA expression in the IML; the results correlated with neurons labeled for proPACAP mRNA by in situ hybridization histochemistry and implicated PACAP biosynthesis in IML neurons. To demonstrate directly proPACAP transcript expression in preganglionic projection neurons to the SCG, the ganglion was decentralized and the sympathetic trunk immersed in fluorogold to identify sympathetic preganglionic neurons by retrograde labeling. Cryosections of spinal cord segments containing preganglionic neuron fluorogold labeled neurons were processed subsequently for in situ hybridization histochemical localization of proPACAP mRNA using a digoxigenin-labeled riboprobe; IML neurons were examined for fluorogold and digoxigenin/alkaline phosphatase product dual labeling. More than half of the preganglionic projection neurons to the SCG expressed PACAP mRNA, consistent with the postulate that PACAP peptides released from a subpopulation of thoracic IML preganglionic neurons may be physiological anterograde modulators of sympathetic SCG function.
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PMID:Pituitary adenylate cyclase activating polypeptide (PACAP) expression in sympathetic preganglionic projection neurons to the superior cervical ganglion. 973 69

Glucagon and peptide of the neuropeptide Y (NPY) family immunoreactivities were studied in the gut of sea bass (Dicentrarchus labrax) using antisera against bovine/porcine glucagon, porcine glucagon, glicentin (10-30), bovine pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), salmon PYY (sPYY), and NPY. Glucagon-, glicentin-, PYY-, and NPY-immunoreactive (ir) cells were detected in the stomach, and glucagon-, PP-, PYY-, sPYY-, and NPY-ir cells in the intestine. PP, PYY, and NPY immunoreactivities coexisted in intestinal endocrine cells (NPY-like peptide containing cells), in some of which there was also glucagon immunoreactivity. Preabsorption tests indicated that different products of the glucagon gene(s) are probably expressed in the stomach and intestine of sea bass and that the peptides belonging to the NPY family in the endocrine cells of the intestine are more similar to NPY than to other peptides of this family. Glucagon-ir cells in the stomach, and glucagon/NPY-like containing cells in the intestine, were characterized by conventional and immunogold electron-microscopic techniques. The glucagon cells had secretory granules with a clotted content, the gold particles being observed in both the core and the halo. Glucagon/NPY-like cells showed two types of secretory granules differing in size, both of which were immunogold labeled with anti-NPY and anti-sPYY; the smaller granules were weakly immunogold labeled with anti-glucagon.
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PMID:Glucagon- and NPY-related peptide-immunoreactive cells in the gut of sea bass (Dicentrarchus labrax L.): a light and electron microscopic study. 974

A growing body of evidence indicates that a number of peptides expressed in the mammalian hypothalamus are involved in the regulation of food intake and energy balance. Among these, melanin-concentrating hormone (MCH) and neuropeptide Y (NPY) are potent appetite stimulants, whereas alpha-melanocyte-stimulating hormone (alpha-MSH), neurotensin, and glucagon-like peptide (GLP)-1(7-36) amide have appetite-suppressing properties. However, the functional interactions between pathways involving these neuropeptides remain incompletely understood. In the current study, we describe the functional interactions between orexigenic (appetite-stimulating: MCH and NPY) and anorectic (appetite-suppressing: alpha-MSH, neurotensin, and GLP-1) peptides after intracerebroventricular (i.c.v.) administration in the rat. The i.c.v. administration of GLP-1 completely prevents the orexigenic effects of both MCH and NPY. However, i.c.v. administration of alpha-MSH prevents only the orexigenic effect of MCH, as we have previously shown, but does not prevent the effect of NPY on food intake. Similarly, i.c.v. administration of neurotensin prevents only the orexigenic effect of MCH, but does not prevent the appetite-stimulating effect of NPY. Thus, our study suggests that the functional interactions between these neuropeptides are specific, although the underlying mechanisms are as yet unexplored.
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PMID:Functional interactions between melanin-concentrating hormone, neuropeptide Y, and anorectic neuropeptides in the rat hypothalamus. 979 36

Appetite-related neuropeptide systems have not been studied extensively in the ruminant, although there have been a number of recent studies of the hypothalamus. Since some leptin signaling is integrated in the rodent brainstem, and leptin modulates neuropeptidergic activity, we now describe leptin receptor (long splice variant, OB-Rb), neuropeptide Y (NPY) and glucagon-like peptide-1 (GLP-1) gene expression in the ovine brainstem. Leptin receptor mRNA was localized to the spinal trigeminal tract and nucleus, nucleus of the solitary tract (NTS), area postrema and dorsal motor nucleus of the vagus. NPY gene expression was abundant in the ovine medulla, occurring in two bilateral 'bands' that encompassed the NTS region and ran ventrolaterally. GLP-1 mRNA was confined largely to the NTS. The distribution of OB-Rb mRNA overlapped with that of NPY and GLP-1 gene expression, suggesting the possibility of interaction between leptin and these brainstem neuropeptide systems. However, in an extension of earlier work, co-expression studies in the murine brainstem revealed only a small number of neurons that expressed both NPY and leptin receptor mRNA, despite the widespread and abundant expression of the former. Thus the majority of NPY synthesis in the brainstem may not be directly regulated by leptin. The sheep brainstem had similar anatomical distribution of OB-Rb, NPY and GLP-1 gene expression to the rodent, consistent with a role for this region in peripheral leptin feedback signaling and brainstem-hypothalamo communication.
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PMID:Association of leptin receptor (OB-Rb), NPY and GLP-1 gene expression in the ovine and murine brainstem. 980 19

Understanding of islet embryogenesis may prove to be key in the design of future therapies for diabetes directed at re-initiating islet growth, with the goal to replace and/or replenish the impaired beta-cell mass in the disease. In this context, studies of islet neurohormonal peptides, known to play a role in the local regulation of islet function, and their expression during islet embryogenesis are important. Here we review our studies on the embryonic islet expression of islet amyloid polypeptide (IAPP) and the PP-fold peptides pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY). IAPP, which is constitutively expressed in beta- and delta-cells in the adult rat, was found to occur in the assumed pluripotent islet progenitor cell, together with PYY, glucagon, and to a lesser extent with insulin. As development proceeds, the insulin/IAPP phenotype is segregated from that of PYY/glucagon; with the formation of islet-like structures, insulin/IAPP-expressing cells primarily occupy their central portions, while PYY/glucagon-expressing cells are found in their periphery. At the time of formation of islet-like structures, expression of NPY is induced in the insulin/IAPP-containing cells. Whereas NPY-expression ceases at birth, PYY is constitutively expressed in non-beta-cells in the mature rat. Expression of PP is induced just prior to birth in a separate population of islet cells, occasionally co-expressed with PYY. Although a clear role for these peptides during embryogenesis has not been identified, they conceivably could play a role in the control of insulin secretion, islet growth and islet blood flow.
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PMID:Expression of non-classical islet hormone-like peptides during the embryonic development of the pancreas. 984 72

Central nervous system glucagon-like peptide-1-(7-36) amide (GLP-1) administration has been reported to acutely reduce food intake in the rat. We here report that repeated intracerebroventricular (i.c.v.) injection of GLP-1 or the GLP-1 receptor antagonist, exendin-(9-39), affects food intake and body weight. Daily i.c.v. injection of 3 nmol GLP-1 to schedule-fed rats for 6 days caused a reduction in food intake and a decrease in body weight of 16 +/- 5 g (P < 0.02 compared with saline-injected controls). Daily i.c.v. administration of 30 nmol exendin-(9-39) to schedule-fed rats for 3 days caused an increase in food intake and increased body weight by 7 +/- 2 g (P < 0.02 compared with saline-injected controls). Twice daily i.c.v. injections of 30 nmol exendin-(9-39) with 2.4 nmol neuropeptide Y to ad libitum-fed rats for 8 days increased food intake and increased body weight by 28 +/- 4 g compared with 14 +/- 3 g in neuropeptide Y-injected controls (P < 0.02). There was no evidence of tachyphylaxis in response to i.c.v. GLP-1 or exendin-(9-39). GLP-1 may thus be involved in the regulation of body weight in the rat.
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PMID:Repeated intracerebroventricular administration of glucagon-like peptide-1-(7-36) amide or exendin-(9-39) alters body weight in the rat. 988 31

We investigated the effect of various neuropeptides present in the prostate, including calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP), substance P (SP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin (CT), leucine-enkephalin (L-ENK), glucagon and parathyroid hormone-related protein (PTH-rP), on the invasion of PC-3 prostate cancer cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. Both CGRP and GRP increased the invasive capacity of tumor cells, whereas SP inhibited it. On the other hand, VIP, CT, L-ENK, NPY, glucagon and PTH-rP had no significant effect. Both CGRP and GRP also increased the haptotactic migration of tumor cells to fibronectin, but SP inhibited it. These three neuropeptides had no effect on either adhesion to fibronectin and laminin or on the gelatinolytic activities of MMP-9 in gelatin zymography, nor did they affect the growth of tumor cells at concentrations used in this study. These results indicate that both GRP and CGRP increased the invasive potential of PC-3 cells probably through enhancement of cell motility, while SP inhibited the invasiveness through suppression of motile response.
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PMID:Effect of prostatic neuropeptides on invasion and migration of PC-3 prostate cancer cells. 992 57

Neuropeptides are essential for the regulation of appetite and body weight within the hypothalamus. The understanding of the neuropeptide regulation of energy homeostasis has been greatly advanced by the recent discovery of leptin, the protein product of the obese gene (ob). Significant new insights into the relationship between peripheral adiposity signals and their impact on the hypothalamic neuropeptide signaling circuitry have provided some crucial missing links in the negative-feedback regulation of appetite and body weight. The neuropeptide Y orexigenic network is a final common pathway for this signaling cascade and, along with feeding-inhibitory neuropeptides such as melanocortin, corticotropin-releasing factor and glucagon-like peptide 1, it is a major target through which leptin exerts a regulatory tonic restraint on body adiposity.
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PMID:Feeding and body-weight regulation by hypothalamic neuropeptides--mediation of the actions of leptin. 1009 45


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