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)

Glucagon injected subcutaneously or intramuscularly may take up to 30 min to reverse hypoglycaemia. We investigated whether glucagon absorption could be accelerated by two manoeuvres known to enhance insulin absorption: addition of a powerful local hyperaemic agent (10 nmole alpha-calcitonin gene-related peptide; CGRP), and injection using a multihole 'sprinkler' needle. Glucagon (1 mg) given by conventional injection to six normal subjects produced peak plasma glucagon concentrations of 1.48 +/- 0.23 (SEM) ng ml-1 after 20 min and a peak glycaemic response of 7.8 +/- 0.8 mmol l-1 at 25 min. Glucagon injected with CGRP or using the sprinkler needle did not produce any significant differences in plasma glucagon or glycaemia profiles, compared with conventional injection. Further studies demonstrated that glucagon is itself a powerful vasodilator, causing a 300-500% increase in local blood flow, comparable to that induced by CGRP. Because of its intense local hyperaemic action, the absorption of subcutaneously-injected glucagon may be optimal and seems unlikely to be accelerated by pharmacological or other means.
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PMID:Attempts to accelerate glucagon absorption: effects of adding a vasodilator and of injection using a 'sprinkler' needle. 163 39

To study the influence of the pancreatic neuropeptides, galanin and calcitonin gene-related peptide, on insulin and glucagon secretion in man, synthetic porcine galanin (80 pmol.kg-1.min-1; N = 6) or synthetic human calcitonin gen-related peptide (10 pmol.kg-1.min-1; N = 5) was infused intravenously in human volunteers. Following 5 min of infusion, arginine (5 g bolus + 10 mg.kg-1.min-1) was given. Galanin did not affect basal or arginine-stimulated insulin secretion judged from determinations of plasma insulin and C-peptide. Similarly, galanin did not affect arginine-stimulated glucagon secretion. Calcitonin gene-related peptide did not affect basal or arginine-stimulated insulin or glucagon secretion. However, calcitonin gene-related peptide slightly potentiated the arginine-induced hyperglycemia (p less than 0.01). Thus, in man, galanin has no influence on insulin or glucagon secretion when infused at 80 pmol.kg-1.min-1, whereas CGRP at 10 pmol.kg-1.min-1 induces slight hyperglycemia.
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PMID:Effects of galanin and calcitonin gene-related peptide on insulin and glucagon secretion in man. 170 74

Culturing sympathetic ganglion neurons in vitro may modify phenotypic expression of some neurotransmitters. For dorsal root ganglia (DRG), contradictory results have been reported; most studies have used immature material. We have therefore performed a detailed immunocytochemical analysis of the transmitter content of cultured adult rat DRG neurons. To demonstrate possible modifications of neurotransmitter phenotypes, we have compared the results obtained with the same techniques on neurons cultured for 3 days and on freshly dissociated DRG cells. Also, the transmitter profile of cultured neurons was compared with that known from in situ studies. Out of 22 antigens studied, 20 were detected in cultured DRG neurons. All of them were expressed in small and/or intermediate-sized cells. Large neurons only contained CGRP, VIP, NPY, beta-END, ENK, and GABA. The percentage of immunostained neurons varied for the various antisera: less than 10% of cultured neurons were positive for ENK, beta-LPH, beta-END, DYN, VASO, and OXY; 10-30% for SOM, CCK, CAT, and SP; and greater than 30% for NPY, CRF, GLU, NT, VIP, GABA, GRP, CGRP, 5-HT, and TRH. In the latter two groups of transmitters (except CGRP), the proportion of immunoreactive neurons was by far larger in cultured than in freshly dissociated DRG. The most pronounced (greater than 25%) increase in the proportion of positively stained neurons after culturing was observed for the GRP, CRF, TRH, and 5-HT antisera. Serotonin was the only transmitter identified in cultured but not in freshly dissociated cells. These data indicate, on one hand, that various antigens, for example, CAT, GABA, NT, TRH, NPY, beta-LPH, and beta-END, which up to now have not been described in DRG in situ, can be detected immunocytochemically a few hours after dissociation of adult rat DRG. On the other hand, several transmitters, for example, VIP, NPY, SP, GABA, GLU, NT, GRP, CRF, TRH, and 5-HT, are expressed in a significantly higher proportion of cells in cultured than in freshly dissociated preparations. This might reflect a change in the phenotypic expression of transmitters due to the new environment generated by the culture conditions, a hypothesis that can be tested by measuring specific mRNA levels. Moreover, considering the plasticity and multipotentiality of their transmitter phenotype, cultured adult DRG neurons might represent an interesting material for autografts into the injured central nervous system.
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PMID:Neurotransmitter phenotype plasticity in cultured dissociated adult rat dorsal root ganglia: an immunocytochemical study. 256 40

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional, and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-alpha were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3-30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.
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PMID:Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects. 283 87

Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.
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PMID:Endocrine cells producing regulatory peptides. 329 70

Both substance P (SP) and calcitonin gene-related peptide (CGRP; 0.13 micrograms.min-1.kg-1 for 10 min) produced a significant rise in arterial plasma pancreatic polypeptide (PP) concentration, and additive responses were obtained when both peptides were infused simultaneously and/or with acetylcholine (0.7 micrograms.min-1.kg-1 ia). The PP response to SP was abolished by intravenous infusions of glucose, whereas those to CGRP and acetylcholine were not significantly affected. Neither SP nor CGRP had any effect on plasma insulin concentration, either in the presence or absence of exogenous glucose, whether infused singly or together, or in the presence of acetylcholine. SP, but not CGRP, produced a small but statistically significant rise in mean plasma glucagon concentration when infused together with acetylcholine. These results suggest that SP and CGRP may modulate the secretion of PP and glucagon in the normal conscious calf but not that of insulin. It is also possible that SP modulates secretion of pancreatic glucagon in these animals.
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PMID:Pancreatic endocrine responses to substance P and calcitonin gene-related peptide in conscious calves. 752 77

Histological, immunocytochemical and immunofluorescence methods were employed to study the oesophagus and stomach of the elephant. The histological findings were in line with the situation in monogastric species like swine and man. In the mucosa of the stomach, endocrine cells were immunoreactive to gastrin, somatostatin, chromogranin A and serotonin. Nerve cells immunoreactive to somatostatin, bombesin, VIP, PHI and CGRP were detected in the submucosal and myenteric plexus of the stomach. In the stomach, the absence of glucagon cells and the presence of endocrine cells immunoreactive to PYY, are in contrast to the situation in mammals and need further investigation. Small gastric ulcers were observed in some of the specimens.
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PMID:The oesophagus and stomach of the African elephant: a histological, immunocytochemical and immunofluorescence study. 759 75

Challenge of intact hepatocytes with amylin only succeeded in elevating intracellular cyclic AMP levels and activating phosphorylase in the presence of the cAMP phosphodiesterase inhibitor IBMX. Both amylin and CGRP similarly activated adenylate cyclase, around 5-fold, although approximately 400-fold higher levels of amylin were required to elicit half maximal activation. Amylin activated adenylate cyclase though apparently simple Michaelien kinetics whereas CGRP elicited activation by kinetics indicative of apparent negative co-operativity. Use of the antagonist CGPP(8-37) showed that both CGRP and amylin activated hepatocyte adenylate cyclase through a common receptor by a mnemonical mechanism where it was proposed that the receptor co-existed in interconvertible high and low affinity states for CGRP. It is suggested that this model may serve as a paradigm for G-protein linked receptors in general. Amylin failed to both stimulate inositol phospholipid metabolism in hepatocytes and to elicit the desensitization of glucagon-stimulated adenylate cyclase. Amylin did, however, elicit the phosphorylation of the inhibitory guanine nucleotide regulatory protein Gi-2 in hepatocytes and prevented the action of insulin in reducing the level of phosphorylation of this G-protein.
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PMID:Regulation of hepatocyte adenylate cyclase by amylin and CGRP: a single receptor displaying apparent negative cooperatively towards CGRP and simple saturation kinetics for amylin, a requirement for phosphodiesterase inhibition to observe elevated hepatocyte cyclic AMP levels and the phosphorylation of Gi-2. 792 19

The GI tract is one of nature's great pharmacies. Most, if not all, biologically active peptides can be found there, and it is quite likely that others remain to be discovered. Our ability to exploit this resource has expanded considerably over the past two decades. Advances in analytical techniques have allowed investigators to rapidly isolate and purify new compounds from tissue extracts. Sequencing and de novo synthesis of newly discovered peptides are now routine, and the structural modifications required to alter activity and tailor a compound to a particular use are easily made. A number of gastrointestinal peptides or their analogues for use in clinical studies are available from commercial sources (see Table 7). Somatostatin is the first gut peptide to successfully complete development and yield a pharmaceutical compound with a broad range of action. Several of the peptides discussed in this article have similar potential. TRH stands out as a candidate because of its effectiveness in the treatment of experimental spinal cord injury and a variety of shock states. Such a broad range of action in critical fields may justify the intensive development required to yield potent, long-acting, and highly specific analogues. Similarly, the antimetastatic and immunostimulant properties of the enkephalins offer promise for new therapies in the treatment of AIDS, ARC, and cancer. Studies with amylin may lead to new and more precise regimens of blood sugar control in insulin-dependent diabetics and could in turn, prevent some of the worst long-term effects of the disease. The development of effective intranasal forms of GHRH could spare children with GH-GHRH deficiency the distress of repeated injections and help to prevent excessive GH blood levels. Secretin, glucagon, or CGRP might be used one day in cardiovascular emergencies, and VIP or its analogues could prove effective in the treatment of asthma. Although preliminary results with many of these peptides are encouraging, further progress will require the development of standardized experimental models and a more rigorous approach to experimental design. Many of the studies reported here suffered from small patient numbers, a narrow or nonexistent range of doses, or the use of only one or two dosing regimens. Lack of objective criteria for determining the level of response, e.g., in studies of mental illness or degenerative diseases, and the ethical problems of withholding treatment from some patients to establish proper controls further hamper research in this area. If the questions of efficacy and safety are to be resolved, thorough, well-planned trials will be required.
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PMID:Therapeutic uses of gastrointestinal peptides. 812 75

Amylin is a recently discovered 37 amino acid peptide secreted into the bloodstream, along with insulin, from pancreatic beta-cells. It is about 50% identical to calcitonin gene-related peptides (CGRP alpha and CGRP beta) and structurally related to the calcitonins. Amylin can elicit the vasodilator effects of CGRP and the hypocalcaemic actions of calcitonin, while these peptides can mimic newly discovered actions of amylin on carbohydrate metabolism. The different relative potencies of these peptides suggest that they act with different selectivities at a family of receptors. Amylin is deficient in insulin-dependent diabetes mellitus, while plasma levels are elevated in insulin-resistant conditions such as obesity and impaired glucose tolerance. In this Viewpoint article, Tim Rink and colleagues propose that amylin is an endocrine partner to insulin and glucagon; deficiency or excess of amylin may therefore contribute to important metabolic diseases.
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PMID:Structure and biology of amylin. 851 54


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