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

ATP-sensitive potassium channels (KATP) are the ion channels which are closely associated with cellular metabolism. A number of chemical compounds which block KATP facilitate the release of hormones or neuropeptides. For example, KATP-blocking agents such as antidiabetic sulfonylureas and imidazolines stimulate insulin secretion from pancreatic beta-cells by decreasing KATP activity. On the other hand, so-called potassium channel openers, KATP-activating drugs which constitute a chemically diverse group of compounds, inhibit growth hormone secretion from anterior pituitary cells and release of gamma-aminobutylic acid from substantia nigra. Several endogenous substances also modulate release of hormone or neuropeptide by affecting KATP activity. Acetylcholine and histamine stimulate the release of endothelium-derived hyperpolarizing factor, which activates KATP in the plasma membrane of vascular smooth muscle cells. Both galanin and somatostatin inhibit insulin release from pancreatic beta-cells by opening KATP through the activation of G-protein. Glucagon-like peptide-1[7-36], which stimulates insulin secretion by indirectly blocking KATP in beta-cells, shows antidiabetic effects in patients with non-insulin-dependent diabetes mellitus. Endosulphine, an endogenous inhibitor of KATP, stimulates insulin secretion from pancreatic beta-cells. Accumulating knowledge of the modulation and function of KATP would help our understanding of the regulation and physiological role of hormones and neuropeptides.
 ...
PMID:[ATP-sensitive potassium channel and hormone/neuropeptide]. 779 22

The neurohormonal structures of two human intestines removed due to rejection 22 months and eight months after intestinal transplantation were studied by an indirect immunohistochemical method and compared with normal ileum. The distribution and density of neurons immunoreactive for tyrosine hydroxylase, substance P, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal peptide, galanin, gastrin-releasing peptide, L-enkephalin, and somatostatin were examined. Mucosal endocrine cells immunoreactive for somatostatin, peptide YY, and glucagon were also examined. Extrinsic adrenergic fibers and perivascular fibers were absent in all intestinal layers of the failed grafts. The distribution of intrinsic neurons was unchanged; however, the density was decreased by one rank. Distribution of endocrine cells of the first graft was similar to the normal. Extrinsic fibers were not detected by immunohistochemistry in human small intestinal grafts following long-term survival and eventual rejection, while the immunohistochemical expression of intrinsic neural and endocrine transmitters were well preserved.
 ...
PMID:Immunohistochemical study of enteric nervous system after small bowel transplantation in humans. 795 15

Because of the enormous growth over the last three decades of research on the role of peptides in the brain, the need became apparent to determine the status of these compounds in terms of their current research interest. Since 1965, over a quarter of a million research papers have been published on peptides that have since been classified as neuroactive. The present study was undertaken to analyze systematically the yearly trends of research emphasis in neuroactive peptides as reflected by their individual frequency of publication by year, beginning in 1966. A computer analysis of the publication characteristics was carried out using the Medline data base in which the citation search was limited to the topic brain crossed with the topic mammal. One criterion for the inclusion of a given peptide in the analysis was a frequency of 25 or more citations following its discovery, as related to the mammalian brain. The 42 peptides that met this criterion were: adrenocorticotropic hormone, angiotensin II, atrial natriuretic factor, bombesin, bradykinin, calcitonin, calcitonin gene-related peptide, carnosine, beta-casomorphin, cholecystokinin, corticotropin-releasing factor, delta sleep-inducing peptide, dynorphin, beta-endorphin, Leu-enkephalin, Met-enkephalin, galanin, gastrin, glucagon, growth hormone, growth hormone-releasing factor, insulin, kyotorphin, beta-lipotropin, luteinizing hormone-releasing factor, melanocyte-stimulating hormone release inhibitory factor-1, alpha-melanocyte-stimulating hormone, motilin, neurokinin A, neurokinin B, neuropeptide Y, neurotensin, oxytocin, pituitary adenylate cyclase activating polypeptide, peptide HI, prolactin, secretin, somatostatin, substance P, thyroid-releasing hormone, vasopressin, and vasoactive intestinal peptide. An overall analysis of the 298,105 papers published on these 42 peptides since 1965 revealed that the research activity of 24,742, or 8.30%, of the studies, focused on their neuroactive properties. Taken as a whole, the research on neuroactive peptides reached a peak in 1986, as reflected by the total of 1793 papers published during that year. Although the level of publication has fluctuated between 1548 and 1774 research papers over the last 6 years, it is now clear that the trend in research on neuroactive peptides has reached an asymptote today that shows no sign of deviation. A temporal analysis year by year of individual publication profiles revealed three distinct trends: 1) peptides showed a slow development in research interest and did not exceed more than 15-30 publications per year; 2) peptides exhibited a steady increase in research activity over the years that continues today; and 3) peptides displayed an initial, often intense, research emphasis that inexplicably declined, in some cases precipitously, in the mid 1980s.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Neuroactive peptides: unique phases in research on mammalian brain over three decades. 800 41

Food intake can be increased or decreased after either central or peripheral administration of peptides. Galanin, neuropeptide Y, opioid peptides, growth hormone releasing hormone and desacetyl-MSH increase food intake whereas insulin, glucagon, cholecystokinin, anorectin, corticotropin releasing hormone, neurotensin, bombesin, enterostatin, cyclo-his-pro and thyrotropin-releasing hormone reduce food intake. A number of these peptides also affect the activity of the sympathetic nervous system. The peptides which have been tested have a reciprocal effect on food intake and sympathetic activity. Opioids, NPY and GHRH, which increase food intake, decrease sympathetic activity. Conversely, peptides which reduce food intake, increase sympathetic activity, with glucagon, cholecystokinin, corticotropin releasing hormone, calcitonin, neurotensin and bombesin being examples, Several of these peptides also affect the intake of specific nutrients. Insulin reduces food intake in animals fed a high carbohydrate diet, but not when fed a high fat diet. Neuropeptide Y increases carbohydrate intake. Galanin and opioid peptides increase fat intake. Enterostatin and cyclo-His-Pro, on the other hand reduce fat intake. Glucagon decreases protein intake. The effect of peptides on the intake of specific nutrients suggests that peptides may work in part by modulating basic feeding mechanisms to lead to the selection of specific nutrients from the diet. This hypothesis might be called a nutrient specific model of peptide-induced food intake.
 ...
PMID:The nutrient balance hypothesis: peptides, sympathetic activity, and food intake. 848 34

The interaction of glucagon-like peptide-I (GLP-I) and galanin in clonal endocrine pancreatic cells was characterized. By Northern blot analysis the presence of GLP-I receptor mRNA was shown in B (beta TC-1 cells) and D (RIN 1048-38) cells but not in A (INR1 G9) cells, thus confirming functional data demonstrating the absence of active GLP-I receptors on glucagon-producing cells. Galanin receptors were detected on B and D cells but not on A cells. In B and D cells galanin inhibited the GLP-I stimulated adenylate cyclase activity. Treatment of insulin- and somatostatin-producing cells with GLP-I increased intracellular cAMP levels, and this was dampened by galanin, GLP-I stimulated the activity of protein kinase A in B and D cells, which was also inhibited by galanin. Galanin alone did not influence B- and D-cell function. These data show that in the endocrine pancreas B and D cells but not A cells express GLP-I and galanin receptors. The interaction of GLP-I and galanin might act in the endocrine pancreas as a physiological inhibitor of the potent incretin hormone GLP-I. Therefore, we suggest galanin is a 'decretin'.
 ...
PMID:Interaction of glucagon-like peptide-I (GLP-I) and galanin in insulin (beta TC-1)- and somatostatin (RIN T3)-secreting cells and evidence that both peptides have no receptors on glucagon (INR1G9)-secreting cells. 859 Jul 87

The insulinotropic glucagon-like peptide 1 (GLP-1) originates from the lower intestines. Surprisingly, food ingestion induces a rapid increase of GLP-1 plasma levels. Therefore, a complex regulation for postprandial GLP-1 secretion must exist, which cannot be solely explained by direct contact of nutrients in the gut lumen with the GLP-1-releasing L cells. This was addressed in the present study utilizing an isolated vascularly perfused rat ileum preparation. Cholinergic (methacholine) as well as peptidergic stimulation by glucose-dependent insulin-releasing polypeptide (synonym: gastric inhibitory polypeptide) (GIP) strongly enhanced GLP-1 secretion from the rat ileum. The stimulation of GLP-1 secretion by methacholine was abolished by addition of atropine and partly reduced by galanin. Galanin dose-dependently antagonized the stimulatory effect of GIP on GLP-1 release. Atropine was without effect. Furthermore, employing double immunohistochemistry labeling techniques galanin-immunoreactive nerves were detected in the vicinity of GLP-1-immunostained cells. Our data indicate that stimulatory and inhibitory mediators regulate GLP-1 secretion and that galanin is a likely inhibitor.
 ...
PMID:Galanin is a potent inhibitor of glucagon-like peptide-1 secretion from rat ileum. 880 63

The first aim of the study was to investigate the possibility that a defect on the islet adenosine 3',5'-cyclic monophosphate (cAMP) production could be involved in the failure of the glucose-induced insulin secretion in the neonatal streptozotocin diabetic rats. Exposure to glucose concentration that induced a rise of the cAMP content in the control islets did not elicit any significant increase in cAMP in diabetic islets. Forskolin, isobutyl methylxanthine (IBMX), glucagon, or pertussis toxin amplified the cAMP accumulation and the insulin release to the same extent in both types of islets. Somatostatin, prostaglandin E2, UK-14304, or galanin inhibited cAMP accumulation and insulin release to the same extent in both types of islets. Our second purpose was to investigate whether the use of activators of adenylate cyclase could restore the beta-cell competence to glucose in diabetic rats. The addition of IBMX, glucagon, or gastric inhibitory polypeptide (GIP) to perifused islets of diabetic rats amplified their insulin response to glucose, and a clear biphasic pattern of the release was regained. In conclusion, although there is no major alteration of the functionality of the adenylate cyclase in the beta-cells of the diabetic rats, we have identified a defective glucose-induced cAMP generation that could be explained by a block in the step(s) linking glucose metabolism and activation of adenylate cyclase.
 ...
PMID:Decreased glucose-induced cAMP and insulin release in islets of diabetic rats: reversal by IBMX, glucagon, GIP. 889 61

betaHC-9 is a pancreatic beta-cell line that is derived from the hyperplastic islets of transgenic mice that express the simian virus 40 tumor antigen gene in the islets. This cell secretes insulin in response to glucose in a concentration-dependent manner. Maximal and half-maximal concentrations were approximately 20 and approximately 10 mmol/l, respectively, with a maximal fractional release that averaged 3.7% of the total cellular insulin content per 60 min. The cellular insulin content was 3-9% of the content of mouse islet cells. Under perifusion conditions, high glucose concentrations induced a sharp first phase that lasted approximately 10 min and a succeeding second phase of sustained release, as exhibited by mouse islets. The cells did not show a rising second phase as seen with rat islets. This biphasic response was obtained without the need for activators of protein kinase A such as forskolin or 3-isobutyl-1-methylxanthine. The dose-dependency and the phasic response to glucose were essentially invariable up to passage 38 but thereafter declined. The cells respond to various well-known stimulators of insulin secretion, including leucine and arginine; to modulators such as carbachol, glucagon-like peptide I, and pituitary adenylyl cyclase activating polypeptide; and to the inhibitors norepinephrine, somatostatin, and galanin. The pharmacological agents glibenclamide, 12-O-tetradecanoylphorbol-13-acetate, and KCl stimulate and forskolin potentiates insulin release. Mannoheptulose, 2-deoxyglucose, and nitrendipine inhibit glucose-stimulated insulin release from the cells. The intracellular Ca2+ concentration was raised by high glucose and by glibenclamide. In conclusion, this cell line preserves the fundamental characteristics of the progenitor normal mouse islets very well. Although several cell lines have been reported to have glucose-responsive insulin secretion, few demonstrate clear biphasic secretion as this cell line displays. In this context, this cell line should serve as a potent tool for studying the mechanisms of insulin secretion, especially the important phasic secretion.
 ...
PMID:The betaHC-9 pancreatic beta-cell line preserves the characteristics of progenitor mouse islets. 892 64

To determine whether galanin is a pancreatic sympathetic neurotransmitter regulating insulin secretion in the baboon, as it is in the dog, we evaluated galanin for inhibitory effects on insulin secretion in conscious baboons, determined if baboon pancreatic islets are innervated by galaninergic fibers using immunohistochemistry, and measured galanin content in the major sympathetic ganglion supplying the pancreas. Surprisingly, infusion of galanin (1 microgram/kg per min) had no effect on arginine-stimulated secretion of either insulin (71 +/- 14 vs. 88 +/- 17 microU/ml; P = NS) or glucagon (104 +/- 12 vs. 94 +/- 9 pg/ml; P = NS). By contrast, growth hormone secretion was markedly increased during galanin infusion. In the baboon celiac ganglion, no galanin immunoreactivity was detectable in sympathetic neuronal cell bodies by immunostaining and their content of galanin-like immunoreactivity, determined by radioimmunoassay, was only 3% of that in dog celiac ganglion (5.2 +/- 0.8 vs. 158 +/- 13 pmol/g; P < 0.001). By contrast, galanin immunoreactivity was observed in many nerve fibers in the baboon exocrine pancreas and occasionally in baboon pancreatic islets. Moreover, galanin content of the baboon pancreas was similar to that of dog (8.7 +/- 1.5 vs. 5.5 +/- 1.2 pmol/g; P = NS). The finding of galanin immunoreactivity in many neuronal cell bodies in baboon intrapancreatic ganglia suggests a parasympathetic source for these galaninergic fibers in the baboon. Together these data demonstrate that galanin is likely to be a parasympathetic neurotransmitter in the baboon pancreas, without major effects on insulin or glucagon secretion.
 ...
PMID:Evidence that galanin is a parasympathetic, rather than a sympathetic, neurotransmitter in the baboon pancreas. 895 79

To study islet function following reduced insulin sensitivity, we examined mice of the C57BL/6J strain, the genotype of which carries an increased propensity to develop insulin resistance when metabolically challenged. The mice received either a high-fat diet (58% fat on an energy basis) or a control diet (11% fat) for 12 weeks. The body weight of mice on the high-fat diet increased significantly more than that of mice on the control diet (25.8 +/- 0.4 v 21.3 +/- 0.2 g, P < .001). Already after 1 week on the high-fat diet, a significant hyperglycemia accompanied by hyperinsulinemia had evolved, indicative of insulin resistance. After 12 weeks, plasma glucose levels for high-fat diet-treated mice were 7.5 +/- 0.1 mmol/L, versus 6.5 +/- 0.1 mmol/L in controls (P < .001); corresponding values for plasma insulin were 248 +/- 17 and 104 +/- 7 pmol/L, respectively (P < .001). Mice given a high-fat diet also had elevated levels of total cholesterol, triglycerides, and free fatty acids (FFAs) compared with controls. After 4, 8, and 12 weeks, glucose (2.8, 8.3, or 16.7 mmol/kg) or the cholinergic agonist carbachol (0.16 or 0.53 micromol/kg) was injected intraperitoneally. The insulinotropic response to glucose was not different between the two groups after 4 or 8 weeks, whereas after 12 weeks, glucose-induced insulin secretion was markedly impaired in high-fat diet-treated mice (P < .001). In contrast, after 8 and 12 weeks on a high-fat diet, carbachol-stimulated insulin secretion was potentiated (P < .01), whereas carbachol-stimulated glucagon secretion was not significantly altered. Furthermore, after 12 weeks on the high-fat diet, insulin secretion from isolated islets was impaired at glucose levels of 8.3, 11.1, and 16.7 mmol/L (P < or = .05). Moreover, islet morphology as examined by immunocytochemistry using insulin antibodies and islet innervation, as revealed by immunostaining of tyrosine hydroxylase (TH), neuropeptide Y (NPY), galanin, vasoactive intestinal polypeptide (VIP), and substance P (SP) were unaffected by the high-fat diet for 12 weeks. However, quantitative in situ hybridization showed a 3.5-fold upregulation of insulin gene expression in response to the high-fat diet (P < .001) despite unaltered B-cell mass and pancreatic insulin content. We conclude that as little as 1 week of treatment with a high-fat diet induces insulin resistance in C57BL/6J mice. This is accompanied later by hyperlipemia, potentiated carbachol-stimulated insulin secretion, and increased insulin gene expression but impaired glucose-stimulated insulin secretion. We suggest that after several weeks' duration, insulin resistance is accompanied by enhanced islet sensitivity to cholinergic activation and exaggerated insulin gene expression, whereas the failing islet sensitivity to glucose represents decompensation.
 ...
PMID:Dissociated insulinotropic sensitivity to glucose and carbachol in high-fat diet-induced insulin resistance in C57BL/6J mice. 900 77


<< Previous 1 2 3 4 5 6 7 8 9 Next >>