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)

The ontogeny of oxytocin receptors in rat forebrain was studied using the selective oxytocin receptor antagonist 125I-d(CH2)5[Tyr(Me)2, Thr4, Tyr-NH29]OVT [( 125I]-OTA). With in vitro receptor autoradiography, binding wa noted on the first postnatal day in dorsal subiculum and thalamus. On postnatal days 5-18, intense labeling was evident in posterior cingulate cortex, dorsal subiculum, lateral septum, and the CA1 subfield of hippocampus. Of these regions only the lateral septum expressed oxytocin receptors in adult brain. Competition studies on coronal sections through posterior cingulate, septum, and dorsal subiculum at P10 demonstrated that transient binding sites in these areas were indeed oxytocin selective (OXY greater than AVP greater tha V1 greater than V2). Result of saturation studies on cingulate membranes from 10-day-old pups agreed favorably with previous reports of the kinetics of [125I]-OTA binding to adult oxytocin receptors (Kd = 0.1 nM in P10 cingulate cortex vs. 0.07 nM for adult ventral subiculum). In contrast to these evanescent developmental sites, oxytocin receptors in the bed nucleus of the stria terminalis and the ventromedial nucleus of the hypothalamus only appeared in adulthood, presumably in response to the surge of gonadal steroids at puberty.
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PMID:Ontogeny of oxytocin receptors in rat forebrain: a quantitative study. 255 21

In the present study, we describe the specificity and the autoradiographic distribution of insulin binding sites in the rat central nervous system (CNS) after in vitro incubation of brain sections with [125I]-14A insulin. Increasing concentrations of unlabeled insulin produced a dose-dependent inhibition of [125I]-insulin binding which represented 92 +/- 2% displacement with 3 X 10(-5) M, whatever the brain sections tested. Half-maximum inhibition with native insulin was obtained with 2.2 X 10(-9) M, with 10(-7) M proinsulin whereas glucagon had no effect. Under our experimental conditions, no degradation of [125I]-insulin was observed. Autoradiograms obtained by apposition of LKB 3H-Ultrofilm showed a widespread distribution of [125I]-insulin in rat CNS. However, quantitative analysis of the autoradiograms with 10(-10) M of labeled insulin, showed a high number of [125I]-insulin binding sites in the choroid plexus, olfactory areas, in both cerebral and cerebellar cortices, the amygdaloid complex and in the septum. In the hippocampal formation, the dorsal dentate gyrus and various subfields of CA1, CA2 and CA3 were labeled. Moreover, arcuate, dorso- and ventromedial nuclei of the hypothalamus contained high concentrations of [125I]-insulin whereas a low density was observed in the mesencephalon. The metabolic role of insulin in the CNS is supported by the large distribution of insulin binding sites in the rat brain. However, the presence of high affinity binding sites in selective areas involved in perception and integrative processes as well as in the regulation of both feeding behavior and neuroendocrine functions, suggests a neuromodulatory role of insulin in the brain.
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PMID:[Radioautographic and quantitative study of insulin binding sites in the rat brain]. 309 89

The location of carbonic anhydrase (CA) isoenzymes I, II and VI in normal and neoplastic pancreatic tissue was studied using polyclonal antisera and the immunoperoxidase technique. Samples were obtained from patients with well-differentiated (n = 4), moderately differentiated (n = 1) and poorly differentiated (n = 4) ductal adenocarcinomas, cystadenocarcinoma (n = 2), adenosquamous carcinoma (n = 1), acinar adenocarcinoma (n = 1), gastrinoma (n = 3), insulinoma (n = 3) and glucagonoma (n = 1). The control specimens were from a patient with traumatic laceration of the pancreas. The normal and malignant endocrine tissue showed intense positive staining for CA I localized in the cells expressing glucagon. In the exocrine pancreatic tissue, CA II was detected in the normal and neoplastic ductal epithelium. No specific staining was detected with anti-CA VI serum in either normal or malignant tissue.
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PMID:Immunohistochemical demonstration of the carbonic anhydrase isoenzymes I and II in pancreatic tumours. 777 97

Glucagon-like polypeptides, GLP-1-(7-36)-amide and GLP-1-(7-37), are important regulators of insulin synthesis and secretion by islet beta-cells. The hypothesis to be tested in this study was that defects in the islet beta-cell GLP-1 receptor gene contribute to the impaired glucose-regulated insulin secretion of non-insulin-dependent diabetes mellitus (NIDDM). Human islet GLP-1 receptor genomic clones were isolated, and two highly polymorphic simple sequence repeat regions (GLP-1R-CA1 and GLP-1R-CA3) were identified. Polymerase chain reaction assays were developed to define alleles. For GLP-1R-CA1, 14 alleles were observed in African-Americans (heterozygosity [het] = 0.78) and 6 alleles in Caucasians (het = 0.67). For GLP-1R-CA3, 16 alleles were observed in African Americans (het = 0.89) and 8 alleles in Caucasians (het = 0.83). By genotyping all members of the 40 reference Centre d'Etude du Polymorphisme Humain pedigrees at GLP-1R-CA3, the human GLP-1 receptor gene was uniquely placed on chromosome 6p between GLO1 and D6S19, 20.4 cM from human leukocyte antigen. To assess the possible role of the GLP-1 receptor gene in determining the genetic susceptibility to NIDDM, allelic frequencies of GLP-1R-CA1 and GLP-1R-CA3 were compared between African-American NIDDM patients (n = 95) and control subjects (n = 93). The frequencies did not differ between the two groups at either GLP-1R-CA1 or GLP-1R-CA3. The GLP-1 receptor gene simple-sequence repeat polymorphisms were used for linkage analysis in Utah Mormon pedigrees (n = 16) with NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human glucagon-like peptide-1 receptor gene in NIDDM. Identification and use of simple sequence repeat polymorphisms in genetic analysis. 819 59

PACAP is a member of the secretin/glucagon/VIP family of peptides and demonstrates neurotrophic and neuroprotective effects at very low concentrations. We have previously shown that PACAP crosses the BBB to a modest degree by way of a saturable transport system. PACAP is transported across the BBB as an intact peptide to enter the parenchymal space of the brain. We tested the possibility that this modest rate of transport would be sufficient to produce the low levels of PACAP needed in the brain to exert a neuroprotective effect against ischemia. We found that PACAP given intravenously could indeed prevent the death of CA1 hippocampal neurons, even if the administration of PACAP was delayed for 24 h after the ischemic event. We suggest that iv PACAP could be neuroprotective after stroke, cardiac arrest, and hypotensive episodes.
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PMID:Transport of pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier and the prevention of ischemia-induced death of hippocampal neurons. 899 9

In order to assess effects of glucagon-like peptide-1 (GLP-1) in the brain excluding the hypothalamus, the effects of GLP-1 (7-36) amide, a naturally produced active fragment, on the electroencephalogram and hippocampal single unit activities of anesthetized male Wistar rats were examined. I.c.v. injection of GLP-1 (7-36) amide decreased the hippocampal theta wave duration. Juxtacellular administration of GLP-1 (7-36) amide first increased and then decreased single unit activities recorded in the hippocampal CA1, which effects were antagonized by exendin (9-39) amide, a GLP-1 receptor antagonist, or 6-cyano-7-nitroquinoxaline-2,3-dione, a non-NMDA type glutamate receptor antagonist. These results indicate that GLP-1 receptors exist in the hippocampus and are involved in modulating hippocampal activity through an increase in the release of excitatory amino acid transmitters.
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PMID:Glucagon-like peptide-1 modulates neuronal activity in the rat's hippocampus. 1050 50

We examined the effects of continuous infusion of exendin (5-39), an antagonist of glucagon-like peptide-1 (GLP-1) receptors, into the rat brain using a mini-osmotic pump on beta-amyloid protein-induced amnesia and apoptosis. Co-infusion of exendin (5-39) with beta-amyloid protein (1-40) prevented the memory impairment and DNA fragmentation in the hippocampal CA1 region observed with infusion of beta-amyloid protein alone. These results indicated a functional role of endogenous GLP-1 in beta-amyloid protein-induced neurotoxicity.
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PMID:Endogenous GLP-1 is involved in beta-amyloid protein-induced memory impairment and hippocampal neuronal death in rats. 1099 51

Pituitary adenylate cyclase-activating polypeptide (PACAP-38) is a member of the vasointestinal polypeptide (VIP)/secretin/glucagon family of neuropeptides for which neuroregulatory functions have been postulated. PACAP-38 receptors are expressed in different brain regions, including hippocampus. In this study, we examined the dose-dependent effects of PACAP-38 on the excitatory postsynaptic field potential (fEPSP) evoked at the Schaffer collateral-CA1 synapse in rat hippocampal slices. Bath application of low dose (0.05 nM) of PACAP-38 induced long-lasting facilitation of the fEPSP. This enhancement was blocked by the cholinergic receptor antagonist atropine and partially by the NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV) and therefore, shares a common mechanism with LTP. In contrast, a high dose (1 microM) of PACAP-38 induced a persistent depression of the fEPSP that was not blocked by antagonists of cholinergic receptors (i.e., atropine and mecamylamine), adenosine receptors (i.e., DCPCX), or glutamatergic NMDA receptors (APV). Intermediate doses (0.1-0.5 microM) of PACAP-38 produced an initial decrease of the fEPSP followed by an enhancement. This decrease was not blocked by atropine whereas the facilitation was. These results show that PACAP-38 modulates CA1 synaptic transmission in a dose-dependent manner and that the peptide interacts with cholinergic and glutamatergic systems.
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PMID:Differential effects of PACAP-38 on synaptic responses in rat hippocampal CA1 region. 1158 73

Previous studies in children with diabetes found that hyperglycemia induces memory dysfunction. In this study, we investigated memory and synaptic plasticity in streptozotocine (STZ)-induced diabetic rats during the juvenile period. We further investigated the effects of glucagon-like peptide-1 (GLP-1) on the diabetes-induced profiles. STZ (85 mg/kg, i.p.) was administered to 17-day-old Wistar rats to induce type-1 juvenile diabetes mellitus (JDM). In the Y-maze test, JDM rats showed significant impairment of learning and memory, which were improved by GLP-1 (7-36) amide (1 microg/5 microl/rat, i.c.v.). Extracellular recording at Schaffer collateral synapses in the CA1 region of hippocampal slices showed that long-term potentiation and paired-pulse facilitation in JDM rats were similar to age-matched control rats. However, the input-output relation was strengthened, and long-term depression (LTD) and responses of N-methyl d-aspartic acid through NR2B subunits were weakened in the JDM rats. GLP-1 (7-36) amide (100 nM) increased the magnitude of LTD and the responses through NR2B in the JDM rats. These results indicate that the lack of LTD and NR2B responses may contribute to impairment of memory associated with JDM, suggesting the potential usefulness of GLP-1 in the treatment of memory dysfunction in JDM.
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PMID:The influences of juvenile diabetes on memory and hippocampal plasticity in rats: improving effects of glucagon-like peptide-1. 1932 Nov 33

Type 2 diabetes has been identified as a risk factor for Alzheimer disease (AD). Insulin signalling is often impaired in AD, contributing to the neurodegeneration seen in AD. Previous studies have shown that the incretin glucagon-like peptide 1 (GLP-1) helps to normalise insulin signalling in type 2 diabetes. GLP-1 also plays important roles in neuronal activity and brain functions. We tested the specific role of GLP-1 receptors in synaptic plasticity and cognitive processes in a GLP-1 receptor knockout (Glp1r(-/-)) mouse model. In an open field assessment, no general difference in exploratory and anxiety was found except for a small decrease in running speed was found (p<0.05). In an object recognition task, Glp1r(-/-) mice explored objects in a similar way to WT controls but did not learn to differentiate between novel and familiar objects (p<0.05) while in an object relocation task, no impairment was observed. In a water maze task, Glp1r(-/-) mice were impaired in the acquisition phase (p<0.001), and also in the probe recall task (p<0.05). LTP in area CA1 of the hippocampus was severely impaired in Glp1r(-/-) mice (p<0.0001). Paired-pulse facilitation was also impaired at 25ms interstimulus interval (p<0.05) but not at longer intervals. The results demonstrate that the murine GLP-1R plays an important role in the control of synaptic plasticity and in some forms of memory formation. The results shed light on the molecular processes that underlie the neuroprotective properties of GLP-1 analogues in animal models of Alzheimer's disease.
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PMID:Impairment of synaptic plasticity and memory formation in GLP-1 receptor KO mice: Interaction between type 2 diabetes and Alzheimer's disease. 1957 62


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