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)

A number of regulatory peptides were investigated for their ability to elevate plasma cAMP. Pituitary adenylate cyclase activating peptide (PACAP)-27, PACAP-38, helodermin, helospectin I and II, vasoactive intestinal peptide (VIP), glucagon, parathyroid hormone (PTH), calcitonin and calcitonin gene-related peptide were among the peptides that were highly effective in raising plasma cAMP when given intravenously in equimolar doses to conscious mice. PACAP-27 and -38 were more effective than any of the other peptides. PACAP 16-38, secretin, gastrin-17, galanin, somatostatin, cholecystokinin-8s, pancreatic polypeptide, substance P, peptide YY and neuropeptide Y were inactive and also did not interfere with the PACAP-27-evoked rise in plasma cAMP levels. Repeated injections of PACAP-27 every 30 min caused a progressive reduction in the plasma cAMP response (measured 5 min after each injection). Forskolin, an activator of adenylate cyclase, dose-dependently raised the plasma concentration of cAMP and displayed a synergistic effect when given in a low dose concurrently with PTH or PACAP-38. The phosphodiesterase inhibitor rolipram dose-dependently raised the plasma concentration of cAMP. Combined treatment with PACAP-27 and a threshold dose of rolipram resulted in an exaggerated plasma cAMP response. Kidney hilus ligation suppressed the responses to PACAP-38, PTH, helodermin, helospectin, VIP, glucagon and calcitonin. Hepatectomy suppressed the response to glucagon but was without effect on the response to the other peptides. Pancreatectomy and spleenectomy reduced the response to VIP, but was without effect on the response to the other peptides. PACAP-27 stimulated cAMP efflux from the isolated rat tail vein. Hence, it cannot be excluded that blood vessels contribute to the peptide evoked plasma cAMP response in vivo.
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PMID:Neuropeptides of the vasoactive intestinal peptide/helodermin/pituitary adenylate cyclase activating peptide family elevate plasma cAMP in mice: comparison with a range of other regulatory peptides. 133 41

The neuropeptide hormone galanin, released by sympathetic stimulation of nerve terminals in the endocrine pancreas, inhibits insulin secretion via a receptor-linked pertussis toxin-sensitive (Gi) transmembrane signaling pathway. Glucagon-like peptide-I(7-37) [GLP-I(7-37)] is an intestinal hormone shown to have potent insulin-releasing activities in pancreatic B-cells and is believed to serve a physiological role in the augmentation of nutrient-induced insulin release. GLP-I(7-37) binds to specific Gs- and adenylate cyclase-coupled receptors on pancreatic B-cells and directly stimulates proinsulin gene transcription, thereby increasing cellular levels of proinsulin messenger RNA (mRNA) and proinsulin biosynthesis. This study examines the effects of galanin on GLP-I(7-37)-stimulated proinsulin gene expression in mouse beta TC1 cells. The degree of proinsulin gene transcription was assessed by measuring the activity of chloramphenicol acetyl transferase (CAT) expressed from a CAT reporter plasmid linked to the rat insulin-1 gene promoter transferred to beta TC1 cells and by measuring proinsulin mRNA levels by Northern blot analysis. Galanin inhibited both CAT activity and the rise in proinsulin mRNA levels stimulated by either GLP-I(7-37) or forskolin (0.1 microM). Notably, galanin was without effect on CAT activity induced by the cAMP analog, 8-bromo-cAMP, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, or higher concentrations of forskolin. The inhibitory effects of galanin on GLP-I(7-37) and forskolin-induced CAT activity were reversed by the addition of pertussis toxin, a toxin that inactivates inhibitory G-proteins (Gi). We conclude that galanin inhibits GLP-I(7-37)-stimulated proinsulin gene expression by inhibiting the activation of adenylate cyclase by GLP-I(7-37) and subsequently the production of cAMP in B-cells. Further, our data suggest that these actions of galanin are mediated by a pertussis toxin sensitive pathway involving one or more Gis that inhibit adenylate cyclase. Thus, in addition to its well known inhibitory effects on insulin secretion galanin can inhibit proinsulin gene expression stimulated by GLP-I(7-37) activation of the cAMP signaling pathway. These findings may be a unique demonstration of the inhibition of proinsulin gene expression by a substance (galanin) released endogenously within the pancreas.
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PMID:Galanin inhibits proinsulin gene expression stimulated by the insulinotropic hormone glucagon-like peptide-I(7-37) in mouse insulinoma beta TC-1 cells. 137 16

It is not known whether sensory nerves are involved in the insulin, glucagon or glucose responses to autonomic nerve activation induced by 2-deoxy-D-glucose (2-DG). We therefore treated mice neonatally with capsaicin which permanently destroys sensory afferent nerve fibers. Immunohistochemistry of the pancreas at 13-14 weeks of age revealed a substantial reduction of calcitonin gene-related peptide (CGRP)-immunoreactive nerves and a partial reduction of substance P-immunoreactive nerves. In contrast, no effect was observed on galanin-immunoreactive nerves. At age 10-12 weeks, the mice were injected intravenously with 2-DG (500 mg/kg). In controls, 2-DG stimulated insulin and glucagon secretion and induced hyperglycemia (P less than 0.01). Capsaicin treatment partially reduced the glucose and glucagon responses to 2-DG (P less than 0.01). In contrast, the insulin response to 2-DG was not affected by capsaicin. It is concluded that the mouse pancreas contains capsaicin-sensitive sensory CGRP- and substance P-immunoreactive nerve fibers, whereas the galanin-immunoreactive nerve fibers are not sensitive to capsaicin. Furthermore, capsaicin-sensitive sensory nerve fibers are partially involved in 2-DG-induced glucagon secretion and hyperglycemia, whereas sensory nerves are not involved in 2-DG-induced insulin secretion.
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PMID:Neonatal capsaicin-treatment in mice: effects on pancreatic peptidergic nerves and 2-deoxy-D-glucose-induced insulin and glucagon secretion. 137 63

To determine whether norepinephrine (NE) and galanin are coreleased during reflex activation of the sympathetic nervous system by hypoglycemia, we administered insulin to halothane-anesthetized (0.8%) dogs and measured the spillover of NE and galanin-like immunoreactivity (GLIR) into pancreatic venous plasma. Insulin injection produced hypoglycemia [plasma glucose (PG) = 34 +/- 3 mg/dl] but did not activate pancreatic noradrenergic (delta pancreatic NE output = +20 +/- 130 pg/min) or galaninergic nerves (delta GLIR output = +40 +/- 50 fmol/min). To determine whether more severe hypoglycemia would activate these nerves, insulin was administered to dogs infused with somatostatin (SS; 2.5 micrograms/min) to block the counterregulatory increase of glucagon secretion. SS reduced the glucagon response to hypoglycemia by greater than 90%, which allowed PG to decrease to 14 +/- 1 mg/dl. Pancreatic NE output increased by 470 +/- 140 pg/min (P less than 0.005); however, pancreatic GLIR output did not increase significantly (delta = +70 +/- 50 fmol/min). When SS was discontinued, pancreatic NE output increased by 490 +/- 200 pg/min (P less than 0.025), and GLIR output increased by an additional +160 +/- 70 fmol/min (P less than 0.025; total delta from baseline = +230 +/- 90 fmol/min, P less than 0.025), suggesting that SS may restrain pancreatic NE and galanin release. Pancreatic NE and GLIR spillover were also increased during severe hypoglycemia when ganglionic neurotransmission was partially impaired with hexamethonium but not when the neural pathway was interrupted by spinal cord transection. We conclude that NE and galanin are coreleased from pancreatic sympathetic nerves when these nerves are centrally activated during severe hypoglycemia in halothane-anesthetized dogs.
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PMID:Corelease of galanin and NE from pancreatic sympathetic nerves during severe hypoglycemia in dogs. 137

Glucose homeostasis is maintained by complex neuroendocrine control mechanisms, involving three peripheral organs: the liver, pancreas, and adrenal gland, all of which are under control of the autonomic nervous system. During the past decade, abundant results from various studies on neuroendocrine control of glucose have been accumulated. The principal objective of this review is to provide overviews of basic adrenergic mechanisms closely related to glucose control in the three peripheral organs, and then to discuss the integrated glucoregulatory mechanisms in hemorrhage-induced hypotension and insulin-induced hypoglycemia with special reference to sympathoadrenal control mechanisms. The liver is richly innervated by sympathetic and parasympathetic nerves. The functional implication in glucoregulation of sympathetic nerves has been well-documented, while that of parasympathetic nerves remains less understood. More recently, hepatic glucoreceptors have been postulated to be coupled with capsaicin-sensitive afferent nerves, conveying sensory signals of blood glucose concentration to the central nervous system. The pancreas is also richly supplied by the autonomic nervous system. Besides the well documented adrenergic and cholinergic mechanisms, the potential implication of peptidergic neurotransmission by neuropeptide Y and neuromodulation by galanin has recently been postulated in the endocrine secretory function. Presynaptic interactions of these putative peptidergic neurotransmitters with the classic transmitters, noradrenaline and acetylcholine, in the pancreas remain to be clarified. It may be of particular interest that it was vagus nerve stimulation that caused a dominant release of neuropeptide Y over that caused by sympathetic nerve stimulation in the pig pancreas. The adrenal medulla receives its main nerve supply from the greater and lesser splanchnic nerves. Adrenal medullary catecholamine secretion appears to be regulated by three distinct local mechanisms: adrenoceptor-mediated, dihydropyridine-sensitive Ca2+ channel-mediated, and capsaicin-sensitive sensory nerve-mediated mechanisms. In response to hemorrhagic hypotension and insulin-induced hypoglycemia, the sympathoadrenal system is activated resulting in increases of adrenal catecholamine and pancreatic glucagon secretions, both of which are significantly implicated in glucoregulatory mechanisms. An increase in sympathetic nerve activity occurs in the liver during hemorrhagic hypotension and is also likely to occur in the pancreas in response to insulin-induced hypoglycemia. The functional implication of hepatic and central glucoreceptors has been suggested in the increased secretion of glucose counterregulatory hormones, particularly catecholamines and glucagon.
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PMID:Sympathoadrenal system in neuroendocrine control of glucose: mechanisms involved in the liver, pancreas, and adrenal gland under hemorrhagic and hypoglycemic stress. 152 Nov 77

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a new member of the secretin/glucagon peptides family, being most homologous to vasoactive intestinal peptide (VIP). The present study was designed to investigate a possible effect of PACAP on the rat gastrointestinal smooth muscle in vitro. We demonstrated that 1) PACAP reduced basal smooth-muscle contractions in all portions of the gastrointestinal tract, but the effect of VIP was region-specific. The inhibitory effect of PACAP in midcolon was approximately 100 times greater than that of VIP. 2) PACAP significantly inhibited smooth-muscle contractions induced by acetylcholine or carbachol. The inhibitory effect of PACAP was not affected by hexamethonium and was additive to the inhibitory effect of atropine and pirenzepine. 3) PACAP inhibited smooth-muscle contractions induced by substance P, cholecystokinin, and galanin, even after atropine treatment. Although the exact mechanism of the inhibitory action of PACAP remains to be clarified, PACAP appears to exert its effect in the rat at a site other than muscarinic receptors, probably through a direct effect on gastrointestinal smooth muscle in vitro.
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PMID:Pituitary adenylate cyclase-activating polypeptide relaxes rat gastrointestinal smooth muscle. 152 72

The effect of galanin on pancreatic hormone release was studied using isolated perifused rat pancreatic islets. In the presence of 100 mg/dl glucose, 10(-8) mol/L galanin significantly inhibited the basal somatostatin release compared with the perifusion without galanin, whereas there was no significant change in the basal insulin and glucagon release. However, under stimulation of 20 mmol/L arginine, 10(-8) mol/L galanin significantly enhanced glucagon release and suppressed insulin and somatostatin release. These effects disappeared immediately after cessation of galanin infusion. Additionally, 10(-8) mol/L galanin significantly enhanced the first and second phase of glucagon release stimulated by arginine, whereas arginine-stimulated insulin and somatostatin releases were significantly inhibited in both phases. In the cysteamine-treated rat islets, neither enhancement of glucagon release nor suppression of insulin release by galanin was reproducible. These findings indicate two possible explanations. First, it is suggested that the effects of galanin on insulin and glucagon release may be direct and reversed by non-specific effect of cycteamine. Secondly, it seems likely that galanin-enhanced glucagon release may be indirect and in part due to the concomitant somatostatin suppression. Galanin may have an important regulatory function on endocrine pancreas.
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PMID:Effect of galanin on arginine-stimulated pancreatic hormone release from isolated perifused rat islets. 168 87

Galanin, a 29 amino acid neuropeptide, was recently isolated from pig intestine. We studied the localization, nature and effect of galanin in pig pancreas. Galanin immunoreactive nerve fibers were regularly found in the pancreas. A peptide chromatographically similar to synthetic galanin was identified in pancreas extracts. The effect of galanin on the endocrine and exocrine secretion was studied in isolated pancreases, perfused with a synthetic medium containing 3.5, 5 or 8 mmol/l glucose and synthetic galanin (10(-10)-10(-8) mol/l). There was no effect on the basal exocrine secretion. The output of insulin, glucagon, somatostatin and pancreatic polypeptide (PP) was measured in the effluent. There was no effect on PP secretion. At a perfusate glucose concentration of 5 mmol/l, galanin at 10(-9) mol/l increased insulin secretion by 55 +/- 14% (mean +/- S.E.M., n = 5) of basal secretion, and at 10(-8) mol/l by 58 +/- 27% (n = 6). At 8 mmol/l glucose, insulin secretion increased by 25 +/- 10% (n = 6) and 62 +/- 17% (n = 8). At 5 mmol/l glucose glucagon secretion was increased by 15 +/- 3% (n = 5) by galanin at 10(-9) mol/l and by 29 +/- 11% (n = 5) by galanin at 10(-8) mol/l, and at 8 mmol/l glucose by 66 +/- 27% and 41 +/- 25%. Somatostatin secretion was inhibited to 72 +/- 2% (n = 5) of basal secretion by galanin at 10(-9) mol/l and to 65 +/- 7% (n = 7) at galanin at 10(-8) mol/l, both at 5 mmol/l glucose. At 8 mmol/l the figures were 83 +/- 6% and 70 +/- 10%. Insulin secretion in response to square wave increases in glucose concentration from 3.5 to 11 mmol/l (n = 5) increased 2-fold during simultaneous perfusion with galanin (10(-8) mol/l).
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PMID:Galanin in the porcine pancreas. 169 4

Results of studies on the effects of exogenous galanin on islet cell secretion are controversial. Until recently, only pig galanin has been available, and structural dissimilarities among the galanin molecules of different species might have contributed to discrepancies among the study results. Thus, we investigated the influence of synthetic rat galanin (50 nM) on unstimulated insulin, glucagon, and somatostatin release and on the responses of these hormones to arginine (10 mM), glucose (16.6 mM), and vasoactive intestinal polypeptide (VIP; 1 nM) in a homologous animal model, the perfused rat pancreas. In addition, the effect of an equimolar concentration of pig galanin on arginine-induced islet cell secretion was examined. Infusion of rat galanin reduced unstimulated insulin release (approximately 60%, P less than 0.01) and the insulin responses to arginine (approximately 30%, P less than 0.025), glucose (100%, P less than 0.01), and VIP (approximately 80%, P less than 0.025). Galanin also inhibited unstimulated somatostatin secretion (approximately 15%, P less than 0.05) and virtually abolished the somatostatin output evoked by arginine, glucose, and VIP. Conversely, rat galanin increased unstimulated glucagon output (approximately 20%, P less than 0.05), potentiated the glucagon response to arginine (approximately 50%, P less than 0.05) and VIP (approximately 90%, P less than 0.05), and counteracted the suppressor effect of glucose on alpha-cell secretion. Pig galanin inhibited the insulin output elicited by arginine (approximately 45%, P less than 0.05) but did not affect the somatostatin and glucagon responses to the aminogenic stimulus. In conclusion, the opposite effects of galanin on insulin and glucagon secretion favor the concept of galanin as a diabetogenic agent. Galanin also behaves as a potent inhibitor of somatostatin release. Finally, the importance of using homologous galanin to study the biological activity of this peptide must be emphasized.
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PMID:Inhibition of insulin and somatostatin secretion and stimulation of glucagon release by homologous galanin in perfused rat pancreas. 169 89

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


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