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1

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Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Insulin Secretion: Effects and Mechanisms (1996)

KARLSSON, SVEN ; MOLLER, KRISTIAN ; SUNDLER, FRANK ; [et al.]

Oxford, UK : Blackwell Publishing Ltd

Annals of the New York Academy of Sciences 805 (1996), S. 0

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ISSN: 1749-6632

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Natural Sciences in General

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1111/j.1749-6632.1996.tb17516.x

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2

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Interleukin-6-deficient mice develop mature-onset obesity (2002)

Wallenius, Ville ; Wallenius, Kristina ; Ahrén, Bo ; [et al.]

[s.l.] : Nature Publishing Group

Nature medicine 8 (2002), S. 75-79

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ISSN: 1546-170X

Source: Nature Archives 1869 - 2009

Topics: Biology , Medicine

Notes: [Auszug] The immune-modulating cytokine interleukin-6 (IL-6) is expressed both in adipose tissue and centrally in hypothalamic nuclei that regulate body composition. We investigated the impact of loss of IL-6 on body composition in mice lacking the gene encoding IL-6 (Il6−/− mice) and found that ...

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1038/nm0102-75

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3

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Galanin-immunoreactive nerves in the mouse and rat pancreas (1991)

Lindskog, Stefan ; Ahren, Bo ; Dunning, Beth Elaine ; [et al.]

Springer

Cell & tissue research 264 (1991), S. 363-368

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ISSN: 1432-0878

Keywords: Galanin ; Tyrosine hydroxylase ; Pancreatic nerves ; Neuropeptide immunocytochemistry ; Adrenergic innervation ; 6-Hydroxydopamine ; Mouse (NMRI) ; Rat (Sprague-Dawley)

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine

Notes: Summary Galanin-containing nerve fibers have previously been observed in the human, dog, and pig pancreas. Whether the mouse and rat pancreas also contain galanin nerve fibers has been a matter of debate. Therefore, we examined the distribution of galanin in the mouse and the rat pancreas. Further, the possible localization of galanin to adrenergic nerves was studied using sequential immunostaining for galanin and tyrosine hydroxylase (TH). In the mouse pancreas, numerous galanin-immunoreactive (GIR) nerve fibers occurred around blood vessels. They were less numerous in the exocrine parenchyma and in association with the islets. In contrast, in the rat pancreas, only a few GIR nerves were found. They were located around blood vessels and scattered in the exocrine parenchyma. Occasionally, GIR nerves were also observed in the islets. There was a dense distribution of TH-immunoreactive fibers in both the mouse and the rat pancreas. Sequential immunostaining revealed co-localization of galanin and TH immunoreactivity in nerve fibers in both the mouse and the rat pancreas. Following chemical sympathectomy using 6-hydroxydopamine (6-OHDA), not all GIR nerves disappeared. In the mouse pancreas a remaining population of galanin nerves was found around blood vessels, and occasionally in the islets. In the rat pancreas, a few GIR nerves were seen also after chemical sympathectomy. We conclude that intrapancreatic GIR nerves also occur in the mouse and the rat. These findings suggest that many of the GIR nerves are adrenergic but that non-adrenergic, possibly intrinsic or sensory GIR nerves exist as well in both the mouse and the rat pancreas.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00313975

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4

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Localization of calcitonin gene-related peptide and islet amyloid polypeptide in the rat and mouse pancreas (1992)

Ahrén, Bo ; Sundler, Frank

Springer

Cell & tissue research 269 (1992), S. 315-322

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ISSN: 1432-0878

Keywords: Calcitonin gene-related peptide ; Islet amyloid polypeptide ; Immunocytochemistry ; Pancreas endocrine, exocrine ; Rat (Sprague-Dawley) ; Mouse (NMRI)

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine

Notes: Summary It was previously demonstrated that the two chemically related peptides calcitonin gene-related peptide (CGRP) and islet amyloid polypeptide (IAPP) both occur in the pancreas. We have now examined the cellular localization of CGRP and IAPP in the rat and the mouse pancreas. We found, in both the rat and the mouse pancreas, CGRP-immunoreactive nerve fibers throughout the parenchyma, including the islets, with particular association with blood vessels. CGRP-immunoreactive nerve fibers were regularly seen within the islets. In contrast, no IAPP-immunoreactive nerve fibers were demonstrated in this location. Furthermore, in rat islets, CGRP immunoreactivity was demonstrated in peripherally located cells, constituting a major subpopulation of the somatostatin cells. Such cells were lacking in the mouse islets. IAPP-like immunoreactivity was demonstrated in rat and mouse islet insulin cells, and, in the rat, also in a few non-insulin cells in the islet periphery. These cells seemed to be identical with somatostatin/CGRP-immunoreactive elements. In summary, the study shows (1) that CGRP, but not IAPP, is a pancreati neuropeptide both in the mouse and the rat; (2) that a subpopulation of rat somatostatin cells contain CGRP; (3) that mouse islet endocrine cells do not contain CGRP; (4) that insulin cells in both the rat and the mouse contain IAPP; and (5) that in the rat, a non-insulin cell population apparently composed of somatostatin cells stores immunoreactive IAPP. We conclude that CGRP is a pancreatic neuropeptide and IAPP is an islet endocrine peptide in both the rat and the mouse, whereas CGRP is an islet endocrine peptide in the rat.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00319623

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5

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Galanin is co-localized with noradrenaline and neuropeptide Y in dog pancreas and celiac ganglion (1990)

Ahrén, Bo ; Böttcher, Gerhard ; Kowalyk, Stephan ; [et al.]

Springer

Cell & tissue research 261 (1990), S. 49-58

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ISSN: 1432-0878

Keywords: Pancreas, exocrine, endocrine ; Celiac ganglion ; Autonomic innervation ; Galanin ; Neuropeptide Y ; Tyrosine hydroxylase ; Coexpression ; Dog

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine

Notes: Summary To visualize the localization and potential colocalization of noradrenaline and the putative pancreatic sympathetic neurotransmitters, galanin and neuropeptide Y (NPY), immunofluorescent staining for galanin, NPY and tyrosine hydroxylase (TH) was performed on sections of canine pancreas and celiac ganglion. In the pancreas, galanin-immuno-fluorescent nerve fibers were confirmed as densely and preferentially innervating the islets, whereas numerous NPY-positive nerve fibers were found in the exocrine parenchyma, the surrounding of the blood vessels and within the islets. Double-staining for the peptides and TH indicated that most galaninpositive nerve fibers were adrenergic, most NPY-positive nerve fibers were adrenergic, and many islet nerves contained both galanin and NPY, although some galaninpositive nerve fibers appeared to lack NPY. In the celiac ganglion, virtually all cell bodies were positive for both galanin and TH; a large subpopulation of these cells were also positive for NPY. Radioimmunoassay (RIA) of galanin in extracts of dog celiac ganglion revealed a very high content (256±33 pmol/g wet weight) of galanin-like immunoreactivity (GLIR), consistent with the dense staining observed. This GLIR behaved in a similar manner to synthetic porcine galanin in the RIA. In addition, the majority of the GLIR in ganglion extracts coeluted with the synthetic peptide upon gel filtration, although a minor peak of a larger apparent molecular weight was also observed, observations consistent with the presence of a precursor peptide. These findings suggest that galanin is a sympathetic post-ganglionic neurotransmitter in the canine endocrine pancreas and that NPY might serve a similar function.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00329437

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6

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Neuropeptide Y: Intrapancreatic neuronal localization and effects on insulin secretion in the mouse (1987)

Pettersson, Magnus ; Ahrén, Bo ; Lundquist, Ingmar ; [et al.]

Springer

Cell & tissue research 248 (1987), S. 43-48

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ISSN: 1432-0878

Keywords: Neuropeptide Y ; Immunohistochemistry ; Pancreas ; Insulin secretion ; Mouse

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine

Notes: Summary The intrapancreatic localization and the effects on basal and stimulated insulin secretion of neuropeptide Y (NPY) were investigated in the mouse. Immunocyto-chemistry showed NPY to be confined to intrapancreatic nerve fibers mainly associated with blood vessels. Fine varicose NPY fibers were also detected in the exocrine parenchyma and occasionally also within the islets. Double-staining experiments with the use of antisera for both NPY and tyrosine hydroxylase (TH) indicated that most of the NPY fibers were nonadrenergic in nature. Only a population of the NPY fibers occurring around blood vessels showed TH immunoreactivity. Under in vivo conditions, NPY was found to elevate plasma insulin levels slightly when injected intravenously at the high dose level of 8.5 nmol/kg. At lower dose levels, NPY did not affect basal plasma insulin levels, but instead inhibited glucose-induced insulin secretion. Thus, the glucose-induced increment in plasma insulin levels, which was 120±7μU/ml in controls, was reduced to 87 ±5 μU/ml by NPY at 4.25 nmol/kg (p〈0.01) and to 98±6μU/ml by NPY at 1.06 nmol/kg (p〈0.05). In contrast, the insulin secretory response to the cholinergic agonist carbachol was not affected by NPY. We conclude that NPY nerve fibers occur in the mouse pancreas and that most of these NPY nerve fibers are nonadrenergic. Furthermore, in the mouse, NPY enhances basal plasma insulin levels at high dose levels and inhibits glucose-induced, but not cholinergically induced insulin secretion at lower dose levels under in vivo conditions.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF01239960

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7

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Cysteamine and the endocrine pancreas: Immunocytochemical, immunochemical, and functional aspects (1989)

Ahrén, Bo ; Böttcher, Gerhard ; Ekman, Rolf ; [et al.]

Springer

Cell & tissue research 256 (1989), S. 159-166

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ISSN: 1432-0878

Keywords: Pancreas, endocrine ; Cysteamine ; Somatostatin ; Insulin secretion ; Glucose ; Immunocytochemistry ; Mouse (NMRI)

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine

Notes: Summary To evaluate the previously reported depletion of pancreatic somatostatin by cysteamine (β-mercaptoethylamine), mice were injected subcutaneously with the drug at 300 mg/kg. Immunocytochemical analysis performed on sections from tissue taken at 4 h after the injection revealed an elimination of somatostatin-14-like immunoreactivity without alterations in the somatostatin-28(1 – 12)-like immunoreactivity. In sections from tissues taken at 24 h after injection, no differences between cysteamine-injected animals and controls were observed. Immunochemical analysis of somatostatin-14-like immunoreactivity in pancreatic extracts showed a significant reduction of the concentration (P〈 0.001). In contrast, no change in the insulin concentration was observed. Functionally, cysteamine lowered the plasma glucose levels at l h after injection; this effect persisted for 6 h. Plasma insulin levels were likewise reduced transiently by cysteamine. Concomitant administration of somatostatin did not influence these effects of cysteamine. The plasma glucose-lowering effect of cysteamine was seen also in alloxan-diabetic mice. We conclude that cysteamine alters the immunoreactive characteristics of pancreatic somatostatin without affecting the immunoreactivity of insulin, and that cysteamine transiently reduces plasma glucose and insulin levels

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00224730

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Presence of galanin in human pancreatic nerves and inhibition of insulin secretion from isolated human islets (1991)

Ahrén, Bo ; Ar'Rajab, Aamer ; Böttcher, Gerhard ; [et al.]

Springer

Cell & tissue research 264 (1991), S. 263-267

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ISSN: 1432-0878

Keywords: Galanin ; Autonomic innervation ; Autonomic ganglia ; Pancreas, endocrine ; Insulin secretion ; Man

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine

Notes: Summary In several animal species, galanin occurs in pancreatic nerves and inhibits insulin secretion. However, the presence and action of galanin in the human pancreas have not been established. Therefore, we examined the presence and nature of human pancreatic galanin-like immunoreactive material (GLIR) and the effects of galanin on glucose-stimulated insulin secretion from isolated human islets. Immunofluorescent staining of human pancreas revealed GLIR in fine varicose fibers in both islets and exocrine parenchyma. Furthermore, acid extracts of pancreas (n=3) and isolated islets (n=3) contained 0.17±0.06 and 0.23±0.11 pmol GLIR/mg protein. Human pancreatic GLIR coeluted with synthetic porcine galanin from Sephadex G-50. Moreover, synthetic porcine galanin inhibited glucose-stimulated insulin secretion from collagenase-isolated human islets at dose rates 〉10-8 M. Thus, (1) human pancreas is innervated by galanin-containing nerves, (2) human pancreatic GLIR is of similar size as synthetic porcine galanin, and (3) porcine galanin inhibits glucose-stimulated insulin secretion from human islets. Therefore, galanin could be an important local regulator of insulin secretion in man.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00313963

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9

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Pituitary adenylate cyclase-activating polypeptide (PACAP): occurrence in rodent pancreas and effects on insulin and glucagon secretion in the mouse (1992)

Fridolf, Tord ; Sundler, Frank ; Ahrén, Bo

Springer

Cell & tissue research 269 (1992), S. 275-279

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ISSN: 1432-0878

Keywords: Pituitary adenylate cyclase-activating peptide (PACAP) ; Immunocytochemistry ; Pancreas, endocrine, exocrine ; Insulin secretion ; Glucagon secretion ; Mouse (NMRI) ; Rat (Sprague-Dawley)

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine

Notes: Summary Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that occurs in several tissues, e.g., in the gut. We have studied PACAP-like immunoreactivity in the pancreas of rat and mouse, and the effects of PACAP-38 on basal and stimulated insulin and glucagon secretion in the mouse. Immunofluorescence staining demonstrated the presence of PACAP-like immunoreactivity in nerve fibers in both the rat and mouse pancreas. The nerve fibers were seen in the exocrine pancreas and surrounding the islets. Occasionally, the nerve fibers occurred within the islets. Most PACAP-positive nerve fibers innervated the intrapancreatic ganglia, although no nerve cell bodies contained PACAP-like immunoreactivity. In-vivo experiments in mice revealed that basal plasma glucagon levels were increased by PACAP-39 injected intravenously at dose levels exceeding 1.8 nmol/kg. Furthermore, PACAP-38 (7 nmol/kg) potentiated the plasma glucagon response to the cholinergic agonist carbachol (0.16 μmol/kg). This potentiation was reduced to simple addition by pretreatment with a combined α- and β-adrenergic blockade by phentolamine (35 μmol/kg) and propranolol (8.5 μmol/kg). Moreover, PACAP-38 inhibited a carbachol-induced increase in the level of plasma insulin in the absence but not in the presence of adrenergic blockade. PACAP-38 increased basal plasma insulin levels and increased basal plasma glucose levels 6 min and 10 min, respectively, after injection of the peptide. We conclude that PACAP-like immunoreactivity exists in nerve fibers innervating the mouse and rat pancreas, particularly the intrapancreatic ganglia, and that PACAP-38 augments both basal and carbachol-stimulated glucagon secretion in the mouse.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00319618

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