Sympathetic Nerve Stimulation Versus Pancreatic Norepinephrine Infusion in the Dog: 1) Effects on Basal Release of Insulin and Glucagon
TL;DR: Whether pancreatic norepinephrine infusions could reproduce the inhibition of insulin secretion and the stimulation of glucagon secretion observed during sympathetic nerve stimulation in halothane-anesthetized dogs was investigated.
Abstract: We investigated whether pancreatic norepinephrine (NE) infusions could reproduce the inhibition of insulin secretion and the stimulation of glucagon secretion observed during sympathetic nerve stimulation in halothane-anesthetized dogs. Three minutes of stimulating the sympathetic nerves (8 Hz, 1 msec, 10 mA, n = 6) surrounding the pancreatic artery decreased both the blood flow in the superior pancreatic vein (SPV) (Δ = -1.7 ± 0.6 ml/min, P < 0.05) and the basal pancreatic output of immunoreactive insulin (IRI) (Δ = –79 ± 5%, P < 0.001). SPV levels of NE increased by 683 ± 177 pg/ml (P < 0.02). Infusion of NE into the superior pancreatic artery at the low dose of 12 ng/min (n = 6) reproduced this increase of SPV levels of NE (Δ= +740 ± 130 pg/ml; P < 0.01) and caused a small reduction of SPV blood flow (Δ= -1.0 ± 0.4 ml/min, P < 0.05), but did not change pancreatic IRI (Δ= -26 ± 16%, NS). The medium dose of NE (120 ng/min, n = 6) reproduced the nerve stimulation-induced decrease of SPV blood flow (Δ= -1....
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TL;DR: It is concluded that islet innervation, through the contribution of all branches of the autonomic nerves and several different neurotransmitters is of importance both for the physiology and pathophysiology of the islets.
Abstract: The pancreatic islets are richly innervated by parasympathetic, sympathetic and sensory nerves. Several different neurotransmitters are stored within the terminals of these nerves, both the classical neurotransmitters, acetylcholine and noradrenaline, and several neuropeptides. The neuropeptides, vasoactive intestinal polypeptide, pituitary adenlyate cyclase activating polypeptide and gastrin releasing peptide are constituents of the parasympathetic nerves, whereas the neuropeptides galanin and neuropeptide Y are localised to sympathetic nerve terminals. Furthermore, the neuropeptide calcitonin gene-related peptide is localised to sensory nerves and cholecystokinin is also an islet neuropeptide, although the nature of the cholecystokinin nerves is not established. Stimulation of the autonomic nerves and treatment with neurotransmitters affect islet hormone secretion. Thus, insulin secretion is stimulated by parasympathetic nerves or their neurotransmitters and inhibited by sympathetic nerves or their neurotransmitters. The islet autonomic nerves seem to be of physiological importance in mediating the cephalic phase of insulin secretion, in synchronising the islets to function as a unit allowing oscillations of islet hormone secretion, and in optimising islet hormone secretion during metabolic stress, e.g. hypoglycaemia and neuroglycopenia. The autonomic nerves could also be involved in the islet adaptation to insulin resistance with possible implication for the development of glucose intolerance and Type II (non-insulin-dependent) diabetes mellitus. It is concluded that islet innervation, through the contribution of all branches of the autonomic nerves and several different neurotransmitters is of importance both for the physiology and pathophysiology of the islets.
843 citations
Cites background from "Sympathetic Nerve Stimulation Versu..."
...In contrast, this does not, however, seem to be the case for basal insulin secretion because although sympathetic nerve stimulation clearly inhibits basal insulin secretion, a local infusion of noradrenaline into the pancreatic artery over a wide dose range increased, not reduced, insulin secretion in the dog [58]....
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...Electrical activation of the sympathetic nerves further induces a large release of noradrenaline into the pancreatic veins [58]....
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...The result of such stimulation is inhibition of basal and glucose-stimulated insulin secretion as evident both in dogs and calves [57, 58]....
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TL;DR: The mechanisms explaining the glucose dependence of the effects of ACh on insulin release are discussed, which involves a marked, PKC-mediated increase in the efficiency of Ca(2+) on exocytosis of insulin granules.
Abstract: Acetylcholine (ACh), the major parasympathetic neurotransmitter, is released by intrapancreatic nerve endings during the preabsorptive and absorptive phases of feeding. In beta-cells, ACh binds to muscarinic M(3) receptors and exerts complex effects, which culminate in an increase of glucose (nutrient)-induced insulin secretion. Activation of PLC generates diacylglycerol. Activation of PLA(2) produces arachidonic acid and lysophosphatidylcholine. These phospholipid-derived messengers, particularly diacylglycerol, activate PKC, thereby increasing the efficiency of free cytosolic Ca(2+) concentration ([Ca(2+)](c)) on exocytosis of insulin granules. IP3, also produced by PLC, causes a rapid elevation of [Ca(2+)](c) by mobilizing Ca(2+) from the endoplasmic reticulum; the resulting fall in Ca(2+) in the organelle produces a small capacitative Ca(2+) entry. ACh also depolarizes the plasma membrane of beta-cells by a Na(+)- dependent mechanism. When the plasma membrane is already depolarized by secretagogues such as glucose, this additional depolarization induces a sustained increase in [Ca(2+)](c). Surprisingly, ACh can also inhibit voltage-dependent Ca(2+) channels and stimulate Ca(2+) efflux when [Ca(2+)](c) is elevated. However, under physiological conditions, the net effect of ACh on [Ca(2+)](c) is always positive. The insulinotropic effect of ACh results from two mechanisms: one involves a rise in [Ca(2+)](c) and the other involves a marked, PKC-mediated increase in the efficiency of Ca(2+) on exocytosis. The paper also discusses the mechanisms explaining the glucose dependence of the effects of ACh on insulin release.
513 citations
TL;DR: A focus in this review has been the multiple control levels that modulate glucagon secretion from glucose and nutrients to paracrine and neural inputs and the glucagon actions on glycaemia and energy metabolism.
Abstract: The secretion of glucagon by pancreatic a-cells plays a critical role in the regulation of glycaemia. This hormone counteracts hypoglycaemia and opposes insulin actions by stimulating hepatic glucose synthesis and mobilization, thereby increasing blood glucose concentrations. During the last decade, knowledge of a-cell physiology has greatly improved, especially concerning molecular and cellular mechanisms. In this review, we have addressed recent findings on a-cell physiology and the regulation of ion channels, electrical activity, calcium signals and glucagon release. Our focus in this review has been the multiple control levels that modulate glucagon secretion from glucose and nutrients to paracrine and neural inputs. Additionally, we have described the glucagon actions on glycaemia and energy metabolism, and discussed their involvement in the pathophysiology of diabetes. Finally, some of the present approaches for diabetes therapy related to a-cell function are also discussed in this review. A better understanding of the a-cell physiology is necessary for an integral comprehension of the regulation of glucose homeostasis and the development of diabetes.
404 citations
Additional excerpts
...Noradrenaline increases glucagon secretion as well (Ahren et al. 1987)....
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TL;DR: It is demonstrated that the innervation of human islets is different from that of mouse islets and does not conform to existing models of autonomic control of islet function.
297 citations
Cites background from "Sympathetic Nerve Stimulation Versu..."
...Selective stimulation of islet innervation is difficult (Ahrén et al., 1987; Bloom and Edwards, 1984)....
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TL;DR: Augmentation des connaissances sur l'importance du controle nerveux des fonctions des ilots sous certaines conditions physiologiques.
Abstract: Augmentation des connaissances sur l'importance du controle nerveux des fonctions des ilots sous certaines conditions physiologiques: le systeme cholinergique est implique avant et pendant l'alimentation et peut-etre aussi dans l'insulino-secretion de l'obesite; le systeme nerveux sympathique controle les ilots pendant le stress; quant aux neuropeptides, leur etude vient a peine de commencer
259 citations
References
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TL;DR: A two antibody system of insulin assay for immunoassay of insulin induces the production of specific nonprecipitating antibodies, both in experimental animals and in humans.
Abstract: It has been demonstrated that insulin induces the production of specific nonprecipitating antibodies, both in experimental animals and in humans.\" Lysis of sensitized red blood cells, paper electrophoresis,\" and salt precipitation have been used in methods of immunoassay of insulin. In a preliminary report the authors described a two antibody system of insulin assay. The present paper describes the method in greater detail and presents results of assays of rat plasma.
2,590 citations
TL;DR: The anatomy of the islet in relation to its vascular supply and both motor and sensory autonomic nerves, which may play a role in altering the secretion rate of islet hormones are described.
Abstract: The islets of Langerhans are richly vascularized and both the islet cells and blood vessels are intimately associated with a variety of autonomic nerves. Direct electrical stimulation of the nerves in vivo or pharmacological stimulation of the islets with neurotransmitters in vitro results in changes in the rate of release of islet hormones. The purpose of this paper is to describe the anatomy of the islet in relation to its vascular supply and both motor and sensory autonomic nerves, which may play a role in altering the secretion rate of islet hormones. Evidence for catecholaminergic, cholinergic, and peptidergic nerves as well as possible peptide neurotransmitters in the pancreas is examined. Secondly, physiological and pharmacological studies are reviewed that reveal how efferent autonomic neural activity leads to altered islet secretion rates. Third, because the complex structure of the islet is supplied with a variety of autonomic nerves, the evidence for excitation of these nerves via reflex activa...
323 citations
TL;DR: Augmentation des connaissances sur l'importance du controle nerveux des fonctions des ilots sous certaines conditions physiologiques.
Abstract: Augmentation des connaissances sur l'importance du controle nerveux des fonctions des ilots sous certaines conditions physiologiques: le systeme cholinergique est implique avant et pendant l'alimentation et peut-etre aussi dans l'insulino-secretion de l'obesite; le systeme nerveux sympathique controle les ilots pendant le stress; quant aux neuropeptides, leur etude vient a peine de commencer
259 citations
TL;DR: Normal subjects were given glucose or tolbutamide alone and during intravenous infusions of norepi-nephrine, and it was concluded that norepinephrine inhibits the release of insulin from pancreatic beta cells.
Abstract: Normal subjects were given glucose (300 mg/ min) or tolbutamide (1 g, intravenously), alone and during intravenous infusions of norepi-nephrine (6 lg/ min). Immunoreactive insulin concentration was less than expected during the infusions of norepinephrine, but returned to higher values after the norepinephrine infusions. From these data it is concluded that norepinephrine inhibits the release of insulin from pancreatic beta cells.
246 citations
TL;DR: In this article, immunoreactive neuropeptide Y (NPY) was demonstrated in neuronal elements in the gut and pancreas of the rat and was demonstrated to play a role in the regulation of intramural neuronal activities, smooth muscle tone, and local blood flow.
Abstract: Immunoreactive neuropeptide Y (NPY) was demonstrated in neuronal elements in the gut and pancreas of the rat. Immunoreactive endocrine cells could not be detected. The occurrence of NPY containing nerve-cell bodies in the submucosal and myenteric ganglia indicates an intrinsic origin of the NPY fibers. However, an additional extrinsic supply of NPY fibers is suggested by the finding that abdominal sympathectomy caused the disappearance of some NPY fibers, notably those around blood vessels. The distribution of NPY fibers in all layers of the gut wall suggests multiple functions of NPY, including a role in the regulation of intramural neuronal activities, smooth muscle tone, and local blood flow.
222 citations