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)

Galanin, a 29 amino acid peptide, inhibits insulin and somatostatin secretion from the isolated, perfused dog pancreas. To assess the nature of the influences of galanin on the endocrine pancreas, we examined the effects of porcine galanin and six different galanin analogues at the equimolar concentration of 1 nmol/l on the hormone release from the isolated, perfused dog pancreas. It was found that galanin2-29 (by 75 +/- 4%), like the native galanin1-29 (by 90 +/- 3%) potently inhibited insulin secretion (p less than 0.001). In contrast, galanin3-29 did not significantly affect insulin secretion. This indicates that removal of the two N-terminal amino acids markedly reduces the potency of galanin. Also, the replacement of the amino acid number 2 (Trp) by Tyr or Phe was followed by a loss of the insulin lowering effect of galanin at this dose level. Likewise, galanin10-29 had no significant effect on insulin secretion. In contrast, the C-terminally deleted galanin1-15 significantly inhibited insulin secretion (by 24 +/- 5%; p less than 0.01), though with a lower potency than did native galanin (p less than 0.05). Consequently, the C-terminal end of galanin is also of importance for the effect. Somatostatin secretion was inhibited by galanin (p less than 0.001), but not by any of the other investigated peptides. Glucagon secretion was not affected by galanin. It is concluded that the two N-terminal amino acids of galanin are essential for the inhibitory action on the insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:On the nature of the galanin action on the endocrine pancreas: studies with six galanin fragments in the perfused dog pancreas. 247 81

Intravenous administration of galanin into fasted conscious dogs produced a dose-dependent hyperglycemia accompanied by decreases in plasma insulin levels, but with no elevation of plasma glucagon levels. Galanin infusions produced greater parenteral glucose-induced rises in plasma glucose levels along with markedly blunted insulin responses compared with glucose and insulin responses to control glucose infusions. Immediately after cessation of the galanin infusions, elevation of plasma insulin levels occurred in the basal state and after parenteral glucose loading. These results suggest that galanin's hyperglycemic activity is predominantly mediated by a reversible inhibition of insulin secretion.
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PMID:Galanin inhibits insulin secretion and induces hyperglycemia in dogs. 257 19

Receptors for regulatory peptides (hormones or neurotransmitters) play a pivotal role in the ability of cells to taste the rich neuroendocrine environment of the gut. Recognition of low concentration of peptides with a high specificity and translation of the peptide-receptor interaction into a biological response through different signalling pathways (adenylyl cyclase-cAMP or phospholipase C-phosphatidylinositol) are crucial properties of receptors. While many new receptors have been identified and thereafter characterized functionally during the 1980s, molecular biology now emerges as the privileged way for the structural characterization and discovery of receptors. Different strategies of receptor cloning have been developed which may or may not require prior receptor purification. Among cloning strategies that do not require receptor purification, homology screening of cDNA libraries, expression of receptor cDNA or mRNA in Xenopus laevis oocytes or in COS cells, and the polymerase chain reaction method achieved great success, e.g. cloning of receptors for cholecystokinin, gastrin, glucagon-like peptide 1, gastrin-releasing peptide/bombesin, neuromedin K, neuropeptide Y, neurotensin, opioids, secretin, somatostatin, substance K, substance P and vasoactive intestinal peptide. All these receptors belong to the superfamily of G-protein-coupled receptors which consist of a single polypeptide chain (350-450 amino acids) with seven transmembrane segments, an N-terminal extracellular domain and a C-terminal cytoplasmic domain. In this chapter, we have detailed the properties of three receptors which play an important role in digestive tract physiology and illustrate various signal transduction pathways: pancreatic beta-cell galanin receptors which mediate inhibition of insulin release and intestinal epithelial receptors for vasoactive intestinal peptide and peptide YY, which mediate the stimulation and inhibition of water and electrolyte secretion, respectively.
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PMID:Receptors for gut regulatory peptides. 751 Sep 49

To determine if dog galanin is a potent inhibitor of dog insulin secretion we determined its primary structure from its cloned cDNA, evaluated its expression in celiac ganglia and determined its effect on islet hormone secretion. The predicted amino acid sequence differs from the other known species of galanin by three to six amino acids in the C-terminal half of the molecule. In situ hybridization revealed the presence of dog progalanin mRNA in every neuronal cell body in the dog celiac ganglion. The predicted dog galanin peptide was synthesized and infused i.v. at 0.25, 2.5, 25 or 250 pmol/kg/min. It potently inhibited insulin secretion, less potently inhibited pancreatic somatostatin release and stimulated glucagon secretion, similar to the effects of porcine galanin in the dog. In summary, dog galanin is expressed in the neuronal cell bodies that innervate the pancreas and the sequence of the dog galanin preserves the potent insulin inhibitory part of the galanin molecule. These data support the hypothesis that galanin is a sympathetic neurotransmitter in dog pancreas.
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PMID:Canine galanin: sequence, expression and pancreatic effects. 751 38

Previous studies demonstrated that porcine galanin is a potent inhibitor of insulin secretion in many species but fails to alter human insulin secretion. To resolve whether this discrepancy was due to the use of a heterologous peptide or to a true species response difference, we studied the effect of a synthetic replicate of human galanin on glucose-stimulated insulin secretion in rats, dogs, and humans. On administration into rats, human and rat galanin significantly inhibited glucose-induced insulin responses to a similar degree. Similarly, porcine and human galanin significantly elevated canine plasma glucose and inhibited canine plasma insulin responses. In contrast, plasma glucose and insulin responses to glucose administration in humans were unaltered by the addition of human galanin at or above the maximum effective dose employed in dogs. Possible effects of galanin administration were seen on human glucagon and pancreatic polypeptide responses to glucose at the highest dose of human galanin infused. We conclude that galanin probably does not play a major role in modulating human beta-cell function.
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PMID:Canine, human, and rat plasma insulin responses to galanin administration: species response differences. 751 57

The metabolic response to graded decreases in insulin concentration was evaluated by measuring the concentration, production, and metabolic clearance rate of glucose in response to the infusion of different galanin doses (1-12 micrograms/kg/h) in 18-h fasted dogs. Peripheral and portal concentrations of insulin and glucagon were measured simultaneously before, during, and after galanin infusions. No increases in portal or peripheral glucagon levels were seen at any dose of galanin infused but, in contrast, dose-dependent decreases of insulin levels occurred in both circulations. The metabolic clearance rate of glucose fell by approximately 25-30% at each dose of galanin infused; suggesting that the maximum effect was reached at the lowest dose. The rate of glucose production increased in a dose-dependent manner with integrated responses of 210 +/- 170, 620 +/- 80, 1,330 +/- 440, 1,920 +/- 310, 1,940 +/- 170, and 1,970 +/- 600 mg/kg at galanin doses of 1, 2, 4, 7, 10, and 12 micrograms/kg/h respectively; saturation of this response occurs at the 7 micrograms/kg/h dose of galanin. The changes in glucose production reflect most closely changes in the fractional decrease in insulin levels both in the portal and peripheral circulations. These changes appear to be mediated by insulin acting directly on the liver, because no alterations in the concentrations of the glucogenic substrates, lactate and glycerol, were seen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of a graded selective suppression of insulin secretion with galanin on glucose production and removal in dogs. 752 64

The endocrine pancreas from 2 genera of lacertid lizards (Pedioplanis and Meroles) was investigated immunocytochemically for the presence of immunoreactivity to mammalian antisera to insulin (I), glucagon (G), pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), neuropeptide tyrosine (NPY), somatostatin 14 (SRIF 14) and somatostatin 28 (SRIF 28), pancreastatin (Pst), galanin (Gl), oxytocin (OT). Cells immunoreactive (IR) to all the antisera used, and nerve fibers IR only to anti-galanin were found. Moreover, three types of colocalized immunoreactivities were detected: type 1 (PP/PYY/NPY), type 2 (G/PP/PYY/NPY), and type 3 (G/PYY/NPY/Pst).
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PMID:The endocrine pancreas of lacertids: an immunocytochemical study of the genera Pedioplanis and Meroles. 754 43

Several gastrointestinal peptides inhibit pancreatic secretion in intact animals, but fail to do so in isolated pancreas preparations. Using isolated perfused porcine pancreas with intact innervation, we studied the influence of such peptides (somatostatin, peptide YY, glucagon-like peptide-1, oxyntomodulin, neuropeptide Y, galanin, and calcitonin gene-related peptide) on vagally induced secretion and on release of vasoactive intestinal polypeptide (VIP), a neuropeptide involved in fluid and bicarbonate secretion. In control experiments electrical vagus stimulation increased flow of juice from 0.9 +/- 0.1 to 37.3 +/- 5.6 ml/h and protein output from 43 +/- 5 to 1,244 +/- 336 mg/h (mean +/- SD). With somatostatin-14 at 10(-10) mol/L, the fluid response was reduced to 64 +/- 11% of controls, protein concentration to 78 +/- 3.8%, and protein output to 50 +/- 5% (p < 0.05). At 10(-8) M the response was almost abolished. VIP release, which in control experiments increased from 0.2 +/- 0.05 to 2.1 +/- 0.4 pmol/min, was similarly reduced (p < 0.01). Galanin at 10(-8) M inhibited the fluid response to 54 +/- 7% of controls, protein output to 51.7 +/- 11%, and VIP release to 54 +/- 6% (p < 0.01). None of the other inhibitory peptides affected vagus responses. It is concluded that somatostatin and galanin inhibit pancreatic secretion through interaction with intrapancreatic ganglia. The other peptides act on extrapancreatic, possibly central sites.
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PMID:Effect of intestinal inhibitory peptides on vagally induced secretion from isolated perfused porcine pancreas. 767 28

Human galanin was recently isolated and sequenced and was found to differ from porcine galanin, hitherto used for studies in humans, in several important respects. We therefore synthesized and purified human galanin and infused it i.v. at a rate of 74 pmol.kg-1.min-1 into six healthy volunteers for 60 min during a hyperglycaemic clamp. The clamp was achieved by i.v. infusion of glucose at a rate which in a control experiment had been demonstrated to maintain the plasma glucose level at 12-13 mmol/l for 90 min. Galanin concentrations reached a plateau of approximately 1500 pmol/l throughout the infusion as opposed to pre-infusion and control levels of 20-30 pmol/l. The glucose levels obtained in the two experiments were indistinguishable. Plasma levels of C-peptide and insulin increased significantly in both experiments and the dynamic concentration curves were almost identical. Glucagon concentrations in plasma decreased significantly and similarly. Growth hormone levels, however, increased eight-fold during galanin infusions. Galanin was eliminated from plasma with a half-life of 3.7 +/- 0.4 min, similar to that of porcine galanin. It is concluded that human galanin powerfully stimulates growth hormone secretion in man, but has no effect on pancreatic endocrine secretion or glucose metabolism in the concentrations obtained in this study.
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PMID:On the effects of human galanin in man. 768 99

Histologically normal liver biopsy specimens from patients with Hodgkin's lymphoma were investigated with three immunohistochemical methods for the occurrence of peptidergic nerve fibers and endocrine cells. Numerous immunoreactive nerve fibers were seen with antisera against peripheral nerves markers (neuron-specific enolase, neurofilament protein, and S-100). These nerve fibers were localized in the tunica media of branches of both the hepatic artery and portal vein, around the bile ducts, and in the connective tissue of the interlobular septa. In the liver, 10 types of peptidergic nerve fibers were detected: glucagon-, glucagon-like peptide- (GLP), somatostatin-, neuropeptide Y- (NPY), vasoactive intestinal polypeptide-, neurotensin-, gastrin/cholecystokinin C-terminus-, substance P-, serotonin-, and galanin-immunoreactive nerve fibers. GLP-, somatostatin-, NPY-, neurotensin-, substance P-, and galanin-immunoreactive nerve fibers were abundant; the other nerve fibers were scarce. The nerve fibers showed two distinct patterns of distribution: they occurred in the blood vessel wall and in connective tissue of the interlobular septum. Pancreatic polypeptide- and NPY-immunoreactive cells were found among the lining epithelial cells of the bile ducts in the interlobular septum.
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PMID:Peptidergic innervation and endocrine cells in the human liver. 769 56


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