Neither adrenergic nor cholinergic antagonists in the central nervous system affect 2-deoxy-D-glucose(2-DG)-induced hyperglycemia

To investigate whether the brain adrenergic and cholinergic neurotransmitter systems are involved in the regulation of 2-deoxy-D-glucose (2-DG)-induced hyperglycemia, we studied the effects of adrenergic and cholinergic antagonists on 2-DG-induced secretion of epinephrine and glucagon, and hyperglycemia, in anesthetized fed rats. When 2-DG (10 mg/10 microliters) was injected into the third cerebral ventricle, hepatic venous plasma glucose, glucagon, and epinephrine concentrations were significantly increased. Co-administration of phentolamine, propranolol, atropine and hexamethonium (1 X 10(-7) mol) with 2-DG did not modify the hyperglycemia and hormonal responses normally observed after the administration of 2-DG alone. From this evidence we concluded that neither brain adrenoceptive nor cholinoceptive neurons are involved in the regulation of 2-DG-induced hyperglycemia.     

Neither adrenergic nor cholinergic antagonists in the central nervous system affect 2-deoxy-d-glucose(2-DG)-induced hyperglycemia

To investigate whether the brain adrenergic and cholinergic neurotransmitter systems are involved in the regulation of 2-deoxy-d-glucose (2-DG)-induced hyperglycemia, we studied the effects of adrenergic and cholinergic antagonists on 2-DG-induced secretion of epinephrine and glucagon, and hyperglycemia, in anesthetized fed rats. When 2-DG (10 mg/10 μl) was injected into the third cerebral ventricle, hepatic venous plasma glucose, glucagon, and epinephrine concentrations were significantly increased. Co-administration of phentolamine, propranolol, atropine and hexamethonium (1 × 10⁻⁷ mol) with 2-DG did not modify the hyperglycemia responses normally observed after the administration of 2-DG alone. From this evidence we concluded that neither brain adrenoceptive nor cholinoceptive neurons are involved in the regulation of 2-DG-induced hyperglycemia.     

Capsaicin-sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetes

The system that regulates insulin secretion from beta-cells in the islet of Langerhans has a capsaicin-sensitive inhibitory component. As calcitonin gene-related peptide (CGRP)-expressing primary sensory fibers innervate the islets, and a major proportion of the CGRP-containing primary sensory neurons is sensitive to capsaicin, the islet-innervating sensory fibers may represent the capsaicin-sensitive inhibitory component. Here, we examined the expression of the capsaicin receptor, vanilloid type 1 transient receptor potential receptor (TRPV1) in CGRP-expressing fibers in the pancreatic islets, and the effect of selective elimination of capsaicin-sensitive primary afferents on the decline of glucose homeostasis and insulin secretion in Zucker diabetic fatty (ZDF) rats, which are used to study various aspects of human type 2 diabetes mellitus. We found that CGRP-expressing fibers in the pancreatic islets also express TRPV1. Furthermore, we also found that systemic capsaicin application before the development of hyperglycemia prevents the increase of fasting, non-fasting, and mean 24-h plasma glucose levels, and the deterioration of glucose tolerance assessed on the fifth week following the injection. These effects were accompanied by enhanced insulin secretion and a virtually complete loss of CGRP- and TRPV1-coexpressing islet-innervating fibers. These data indicate that CGRP-containing fibers in the islets are capsaicin sensitive, and that elimination of these fibers contributes to the prevention of the deterioration of glucose homeostasis through increased insulin secretion in ZDF rats. Based on these data we propose that the activity of islet-innervating capsaicin-sensitive fibers may have a role in the development of reduced insulin secretion in human type 2 diabetes mellitus.     

Insulin and glucagon secretion in the rat: effects of gastrin releasing peptide

Immunoreactive gastrin releasing peptide (GRP) has been shown to occur in intrapancreatic nerve fibers, and to be released from the perfused porcine pancreas during electrical vagal activation. Hence, it could be anticipated that GRP may be of functional importance for the neural control of islet hormone secretion. Therefore, we investigated the effects of intravenous infusion of GRP on basal and stimulated insulin and glucagon secretion in vivo in the rat. We found that GRP, at 4.3 or 17 pmol/min, increased basal plasma concentrations of both insulin and glucagon and induced hyperglycemia. Furthermore, GRP (1.1 or 4.3 pmol/min) potentiated the plasma insulin response to glucose (7 mg/min). In contrast, the peptide (at 4.3 pmol/min) inhibited the insulin response to arginine (8.5 mg/min). Moreover, GRP increased the plasma glucagon levels during infusion of both arginine and glucose. In summary, in the rat GRP 1) stimulates basal insulin and glucagon secretion, 2) potentiates glucose-stimulated insulin secretion, 3) inhibits arginine-stimulated insulin secretion, 4) potentiates arginine-stimulated glucagon secretion, 5) counteracts the glucose-induced suppression of glucagon secretion, and 6) induces hyperglycemia. Though this study can not establish the mechanisms or physiological importance of these effects, we conclude that the intrapancreatic neuropeptide GRP has the capability to affect both insulin and glucagon secretion in vivo in the rat.     

Differential neuropathies in hyperglycemic and hypoglycemic diabetic rats

We investigated the effects of hyperglycemia and hypoglycemia on development of peripheral neuropathy in somatic motor and sensory nerves in type 1 diabetic BB/Wor rats. The animals were maintained in a hyper- or hypoglycemic state by treatment with insulin for 3 months. Nondiabetic siblings served as controls. Qualitative analysis of the gastrocnemius and sural nerves by light and electron microscopy revealed signs of Wallerian-type axonal degeneration and regeneration of large myelinated fibers in the hypoglycemic but not the hyperglycemic animals. Degeneration was more common in the gastrocnemius nerve than in the sural nerve. In hypoglycemic rats, myelinated fibers in both the gastrocnemius and sural nerves had significantly shorter internodes and smaller diameters. The decreased fiber diameter was related (r = -0.9) to the duration of severe hypoglycemia (相似文献   

Guanethidine blocks the 2-deoxy-d-glucose-induced hypothalamic noradrenergic drive to hyperglycemia

To determine whether 2-deoxy-D-glucose (2-DG)-induced hyperglycemia is neurally mediated we administered guanethidine, an adrenergic neuron blocker, to 2-DG-treated rats. While 2-DG increased both medial basal hypothalamic noradrenergic neuronal activity (MBH NNA) and serum glucose, the rise in serum glucose was blocked by guanethidine while MBH NNA was even further increased. We conclude that 2-DG-induced hypothalamic noradrenergic drive to hyperglycemia is mediated by direct sympathetic nervous system activation of liver glucose output.     

Insulin and glucagon secretion in swimming mice: effects of adrenalectomy and chemical sympathectomy

Swimming-stress is known to inhibit glucose-stimulated insulin secretion and stimulate glucagon secretion. In the present study, in mice, we investigated the relative contribution of sympathetic nerves and the adrenals to these effects. Mice were pretreated either with adrenalectomy or chemical sympathectomy induced by i.v. injection of 6-hydroxydopamine (6-OHDA), which destroys sympathetic nerve terminals. Two days later, the mice were injected i.v. with either glucose (5.6 mmol/kg) or saline, immediately before being subjected to 2 min swimming-stress or 2 min resting. Directly thereafter, blood was sampled. In normal controls, swimming inhibited glucose-stimulated insulin secretion and elevated plasma glucagon levels (P less than 0.01). Both these responses were absent both in adrenalectomized and in chemically sympathectomized mice. We also found that in resting animals, adrenalectomy reduced plasma levels of glucagon (P less than 0.05) and glucose (P less than 0.01), and that in adrenalectomized mice, swimming lowered basal plasma insulin levels (P less than 0.05). Furthermore, 6-OHDA-treatment elevated basal plasma glucagon levels (P less than 0.01). Thus, we show that, in the mouse, the inhibition of glucose-stimulated insulin secretion and the stimulation of glucagon secretion that occur during swimming-stress are both dependent on mechanisms requiring both the adrenals and intact sympathetic nerve terminals.     

Biochemical, anatomical and functional correlates of postnatal development of the capsaicin-sensitive innervation of the rat urinary bladder

The postnatal development of substance P-like immunoreactivity (SP-LI) in the urinary bladder (assayed by radioimmunoassay and immunohistochemistry) was investigated in rats and compared with changes in the contractile response to acetylcholine, SP or capsaicin. In adult rats, bladder SP-LI was depleted by systemic capsaicin desensitization or extrinsic bladder denervation indicating that it is completely stored in sensory nerves. Bladder SP-LI was not detected in rat fetuses nor in newborn rats until day 3 of postnatal life (P3). SP-LI increased thereafter to reach, at P20, values approaching 60% of the SP-LI observed in the adult rat. By immunohistochemistry, SP-LI positive varicose fibers were not observed until P13. The contractile response to capsaicin was absent at P0, both in vivo (topical application) and in vitro. In adult rats, the capsaicin-induced bladder contraction was abolished by extrinsic denervation and is produced by release of transmitters from sensory nerves. The amplitude of the capsaicin-induced contraction in the postnatal rat bladder was significantly correlated with SP-LI concentration in the organ. Bladders excised from newborn (P0) or adult rats were equally sensitive to exogenous SP which, in both cases, produced a concentration-related contraction. It is concluded that the postnatal development of the 'efferent' function mediated by capsaicin-sensitive nerves of the rat bladder is strictly related to development of peptidergic sensory innervation.     

Effects of afferent and efferent denervation of vagal nerve on endotoxin-induced oxidative stress in rats

This study investigated the role of vagal innervation in oxidative stress after systemic administration of lipopolysaccharide (LPS) endotoxin. Control rats and rats subjected to bilateral subdiaphragmatic vagotomy, perivagal capsaicin application (5 mg/ml) or cholinergic receptor blockade with subcutaneous atropine (1 mg/kg), were intraperitoneally injected with 300 μg/kg of LPS and euthanized 4 h later. Results indicated that; (1) surgical vagotomy and sensory denervation by perivagal capsaicin increased brain oxidative stress and decreased reduced glutathione in basal condition (saline-treated rats) and following endotoxin challenge; (2) oxidative stress decreased after cholinergic blockade with atropine in endotoxemic rats; (3) nitric oxide decreased by abdominal vagotomy, sensory deafferentation and cholinergic blockade after endotoxin injection; (4) liver lipid peroxidation decreased after surgical vagotomy and cholinergic blockade but increased after sensory deafferentation; (5) liver reduced glutathione decreased following vagotomy and sensory denervation in basal state and by cholinergic blockade in basal state and during endotoxemia; (6) nitric oxide increased by vagotomy in basal state and by sensory denervation and cholinergic blockade in basal state and during endotoxemia; (7) liver histological damage increased by subdiaphragmatic vagotomy, sensory denervation or cholinergic blockade. These findings suggest that: (1) sensory fibers (signals from the periphery) running in the vagus nerves are important in maintaining the redox status of the brain; (2) capsaicin vagal sensory nerves are likely to maintain nitric oxide tone in basal conditions; (3) the vagus nerve modulates liver redox status and nitric oxide release, (4) the vagus nerve mediates protective role in the liver with both cholinergic and capsaicin-sensitive mechanisms being involved.     

The effects of neonatal capsaicin administration on trigeminal nerve chemoreceptors in the rat nasal cavity.

Trigeminal nerve fibers in the nasal cavity respond to a variety of volatile chemical stimuli. Some of these trigeminal nerve fibers have been suggested to be capsaicin-sensitive and thus belong to a class of pain receptor rather than constituting a separate class of chemoreceptor. Our current results confirm this suggestion. Trigeminal nerve responses to volatile chemical stimuli were eliminated in rats which were injected with capsaicin on the second day of life. Animals whose nerves were unresponsive to chemical stimuli also exhibited a loss of intraepithelial peptide-immunoreactive fibers in their nasal cavities. The results of this study suggest that trigeminal nerve fibers in the nasal cavity which respond to chemical stimuli may be polymodal nociceptors which contain substance P, calcitonin gene-related peptide, or perhaps other neuropeptides.     

The contribution of capsaicin-sensitive innervation to activation of the spinal vesico-vesical reflex in rats: relationship between substance P levels in the urinary bladder and the sensory-efferent function of capsaicin-sensitive sensory neurons

In acute spinal rats (C2-C3) the transvesical infusion of saline activates a vesico-vesical excitatory reflex (Brain Res., 380 (1986) 83-93). In bladders containing a subthreshold amount of fluid the topical application of capsaicin on the outer surface of the bladder dome activated this spinal reflex and also produced a transient rise in blood pressure and heart rate. The effects of systemic capsaicin desensitization (50 mg/kg s.c. 5 min, 60 days before) on the sensory (activation of the spinal vesico-vesical reflex) and 'efferent' (tetrodotoxin-insensitive capsaicin-induced contraction) functions mediated by the capsaicin-sensitive sensory fibers were correlated to changes in substance P-like immunoreactivity (SP-LI) content of the urinary bladder in adult rats. Blockade of both sensory and efferent functions was observed at a time (60 min from capsaicin administration) when the SP-LI content of the urinary bladder was unaffected. Four days after capsaicin desensitization the SP-LI levels of the bladder are almost depleted indicating that the neuropeptide(s) are entirely stored in sensory structures. At this time the sensory-efferent functions mediated by these fibers are still blocked. At 15-60 days from systemic capsaicin desensitization there was a progressive, time-related recovery of SP-LI levels in the bladder as well as of the sensory-efferent functions. These findings indicate a role of the capsaicin-sensitive innervation of the urinary bladder in activating the spinal vesico-vesical reflex. The present findings suggest that measurement of SP-LI levels in the rat bladder may be a useful biochemical index for monitoring the function(s) of the capsaicin-sensitive, peptidergic sensory neurons.     

Autonomic nervous control of the endocrine secretion from the isolated, perfused pig pancreas

The effect of electrical stimulation of the splanchnic and the vagus nerve supply to isolated, perfused pig pancreas on the secretion of insulin, glucagon and pancreatic polypeptide (PP) was investigated. Functional integrity of the autonomic nerve supply was assessed by the effect of nerve stimulation on vascular resistance and exocrine secretion. Splanchnic nerve stimulation increased glucagon and PP output (2 to 3-fold) and inhibited insulin output (by 42%). Propranolol abolished the effect on PP and glucagon secretion, but did not affect the inhibition of insulin secretion. Phenoxybenzamine abolished the inhibition of insulin secretion, reduced the effect on glucagon secretion and enhanced the effect on pancreatic polypeptide secretion. Combined alpha- and beta-adrenergic blockade abolished all effects of splanchnic nerve stimulation. Vagus nerve stimulation increased the secretion of all 3 hormones (PP: up to 30-fold, insulin and glucagon: 3 to 5-fold). The effect on insulin and PP-secretion was mimicked by acetylcholine at 10(-7)-10(-6) M, whereas glucagon secretion was inhibited. The effect of vagus nerve stimulation on insulin and PP secretion was augmented by physostigmine, and inhibited (but not abolished) by atropine at 10(-7)-10(-6) M. The effect on glucagon secretion was inhibited by physostigmine and unaffected by atropine. It is concluded that all of the effects of splanchnic nerve stimulation on insulin and PP secretion can be explained by interactions of norepinephrine with excitatory beta-receptors on PP-cells and inhibitory receptors on the insulin cells. Both cell types are also stimulated via muscarinic cholinoceptors, but the partial atropine resistance suggests that other transmitters participate in vagal activation. The nervous regulation of glucagon secretion is complex and may involve the peptidergic innervation of the pancreatic islets.     

Acute intragastric application of capsaicin inhibits 2-deoxy-D-glucose — but not histamine-induced gastric acid secretion in the dog

In this study the influence of acute exposure of gastric mucosa to the sensory neurotoxin capsaicin on basal gastric acid secretion and on secretion induced by 2-deoxy-D-glucose or histamine in conscious dogs with gastric fistulae has been investigated. Under basal conditions intragastric capsaicin (160 microM, 50 ml of volume) did not induce any significant change in acid secretion and in plasma levels of gastrin. Total acid output induced by 2-deoxy-D-glucose (75 mg/kg i.v.) was significantly decreased by intragastric application of capsaicin, while plasma gastrin concentrations were unaffected. A direct stimulant of the parietal cells, such as histamine (64 micrograms/kg s.c.) increased gastric acid secretion which was not sensitive to capsaicin pretreatment. These findings indicate the involvement of capsaicin-sensitive fibers in the control of vagally-induced gastric acid secretion in the dog.     

Hypothalamic Cholinergic Activity and 2-Deoxyglucose-Induced Hyperglycemia

To clarify the role of the hypothalamic cholinergic system in the regulation of peripheral glucose metabolism, we investigated hypothalamic cholinergic activities after administration of 2-deoxyglucose (2-DG). Intravenous administration of 2-DG (500 mg/kg) caused neuroglycopenia and marked hyperglycemia; the level of plasma glucose increased to 210% of the initial levels at 20 min. For evaluation of the cholinergic activity, we employed a microwave device and subsequently analyzed the contents of acetylcholine (ACh) and choline after microdissection of the hypothalamic nuclei, ventromedial hypothalamic nucleus (VMH), lateral hypothalamus (LH), and paraventricular nucleus (PVN). In addition, we analyzed fluctuation of extracellular levels of ACh using in vivo brain microdialysis. A decrease in the ACh content, and a corresponding increase in the choline content, was observed in those hypothalamic nuclei 20 min after administration of 2-DG. In the microdialysis perfusate, on the other hand, extracellular level of ACh was increased by 2-DG administration. These data show that ACh release, which is cholinergic activity, was increased after 2-DG administration. Our results suggest the involvement and importance of the hypothalamic cholinergic system in 2-DG-induced hyperglycemia.     

Ruthenium red antagonism of the effects of capsaicin mediated by extrinsic sensory nerves on myenteric plexus neurons of the isolated guinea-pig ileum.

The effects of Ruthenium red and its antagonism of capsaicin-induced action on the electrophysiological behavior of myenteric neurons were investigated with intracellular recording techniques in the isolated guinea-pig ileum. Ruthenium red antagonized dose-dependently (1-10 microM) a capsaicin-induced marked long-lasting slow depolarizing action associated with increased input resistance, during which the cells spiked repeatedly or displayed anodal break excitation. This action of capsaicin has been found to be mediated via a release of substance P from sensory nerve endings. The slow depolarizing response to exogenous substance P applied by pressure microejection, which mimicked the capsaicin-induced action, was not affected by Ruthenium red. Therefore, present results indicate that Ruthenium red antagonizes the specific effect of capsaicin on myenteric neurons by acting on the presynaptically located peripheral nerve terminals of sensory neurons and inhibiting the release of substance P. Electron-microscopic examination showed that the neurotoxic action of capsaicin towards extrinsic sensory nerve fibers was also dose-dependently (1-10 microM) protected by pretreatment of ruthenium red. Present results suggest that Ruthenium red inhibits a capsaicin-induced activation of cation channels at the cell membrane of sensory nerves.     

Distinct localization and target specificity of galanin-immunoreactive sympathetic preganglionic neurons of a teleost, the filefish Stephanolepis cirrhifer

Immunoreactivity for galanin was examined in the sympathetic preganglionic neurons in the spinal cord, adrenal glands, sympathetic ganglia, and some sensory ganglia of the filefish Stephanolepis cirrhifer. Galanin-immunoreactive neurons were found only in the rostral part, but not in the caudal part of the central autonomic nucleus (a column of sympathetic preganglionic neurons of teleosts). Many galanin-immunoreactive nerve terminals were found in contact with neurons in the celiac ganglia and the cranial sympathetic ganglia on both sides of the body. Most neurons encircled by galanin-immunoreactive nerve fibers were negative for tyrosine hydroxylase. Galanin-immunoreactive nerve fibers were very sparse in the spinal sympathetic paravertebral ganglia. No galanin-immunoreactive nerve fibers were found in the adrenal glands. No sensory neurons of the trigeminal, vagal, or spinal dorsal root ganglia were positive for galanin-immunoreactivity. These results suggest that galanin-immunoreactive sympathetic preganglionic neurons have distinct segmental localization and might project specifically to a population of non-adrenergic sympathetic postganglionic neurons in the celiac and cranial sympathetic ganglia.     

The role of glucose, insulin and glucagon in the regulation of food intake and body weight

Glucose and related pancreatic hormones play a major role in the metabolism of monogastric mammals yet their influence on hunger and/or satiety is, as yet, poorly understood. Glucose, insulin and glucagon rise during a meal and gradually decline to baseline levels shortly after a meal. A sudden drop in plasma glucose as well as insulin have been reported just prior to the onset of a meal but the functional significance of this is not yet clear. Systemic injections of glucose have no acute satiety effects but intraduodenal and intrahepatic infusions reduce food intake and free-feeding and deprived animals respectively. Treatments which decrease cellular glucose utilization directly (2-DG) or indirectly (insulin) increase food intake while exogenous glucagon (which produces hyperglycemia) decreases it. There is considerable evidence that some or all of these effects may be due to a direct central action of glucose, 2-DG, insulin, and glucagon on brain mechanisms concerned with the regulation of hunger and satiety although influences on peripheral "glucoreceptors" have been demonstrated as well. The functional significance of glucoprivic feeding is, however, questioned. The feeding response to 2-DG and related compounds is capricious, and its temporal course does not parallel the hyperglycemic reaction which presumably reflects cellular glucopenia. Moreover, numerous brain lesions which increase, decrease, or have no effect on ad lib intake and often have no effect on the response to deprivation have been shown to severely impair or abolish feeding responses to systemic injections of 2-DG that produce severe central as well as peripheral glucopenia. Feeding responses to insulin are intact after most of these lesions, suggesting that this hormone may influence food intake in a fundamentally different fashion. The mechanism of insulin action is not understood--the classic feeding response is obtained only with doses that are pharmacological when compared to normal plasma levels and there is increasing evidence that lower doses may have opposite, inhibitory effects on food intake and body weight. Relatively small doses of glucagon decrease food intake (although opposite facilitatory effects have been reported after even smaller doses) but the effect does not appear to be due to hepatic mobilization of glucose as initially assumed. Decreases in food intake after intracranial injections of very small doses suggest a direct central action.     

Near nerve local insulin prevents conduction slowing in experimental diabetes

Insulin may have direct effects on axons through its actions on insulin receptors or through cross occupancy of insulin-like growth factor-1 receptors. We tested the hypothesis that insulin itself influences conduction of myelinated fibers independent of hyperglycemia in experimental diabetes. Low dose intermittent (0.2 units thrice weekly) Toronto (regular) insulin was injected at the sciatic notch and knee near the left sciatic nerve of rats rendered diabetic with citrate buffered streptozotocin or nondiabetic rats given citrate only. Identical volumes of normal saline were injected near the contralateral right sciatic nerve. The diabetic rats developed hyperglycemia, elevated glycosylated hemoglobin levels and had slowing of right (saline treated) sciatic tibial motor and caudal sensory conduction velocity. In contrast, local insulin treatment on the left side prevented conduction slowing, unilaterally increasing conduction velocity. In nondiabetic rats, conduction velocities were slightly higher on the insulin treated side, but the influence of insulin was less robust than in diabetics. The insulin treated sural branches of the sciatic nerves in diabetics had a higher percentage of small (≤9.0 μm diameter) myelinated fibers than the saline treated nerves. Local insulin has a trophic influence on myelinated fibers that is prominent in diabetic nerves and is independent of hyperglycemia.     

Capsaicin treatment to developing rats induces increase of noradrenaline levels in the iris without affecting the adrenergic terminal density

The effects of administration of capsaicin to developing and adult Sprague-Dawley rats on substance P-containing primary afferent and peripheral adrenergic nerves were analysed by histochemical and neurochemical techniques. In control rats a relatively dense innervation with substance Pimmunoreactive fibers was seen in the iris, while 10 weeks after a single neonatal injection of capsaicin (50 mg/kg s.c.) a moderate loss of substance P-immunoreactive nerve fibers was observed. The substance P level was decreased by 60%, while the noradrenaline level, ³H-noradrenaline uptake in vitro and the noradrenaline nerve density were unaltered. Repeated injections of capsaicin (2 × 50 mg/kg, 3 × 20 mg/kg s.c.) for 5 weeks to developing rats led to a very marked decrease of the substance P level and an almost complete disappearance of substance P-immunoreactive fibers in the iris, when analysed at 10 weeks of age. The noradrenaline level in the iris was significantly increased (+42%), while no significant changes in noradrenaline level were observed in heart auricula or superior cervical ganglion. The uptake in vitro of ³H-noradrenaline in irides and heart auriculae, as well as the noradrenaline terminal density in the dilator plate and surrounding blood vessels in the iris, were unaffected by repeated capsaicin treatment to developing rats. Capsaicin administration to adult rats (50 mg/kg s.c.), leading to a profound decrease in substance P, did not affect the noradrenaline levels at 24 hr after the injections. The results indicate that an extensive sensory denervation with capsaicin during development can induce an increase of noradrenaline levels in sympathetic nerve terminals in a target area (rat iris) with a rich SP-ergic sensory innervation, although the sympathetic terminal density is not influenced. Furthermore the increase in noradrenaline seems to require an extensive loss of SP-immunoreactive fibers and not solely a reduction of SP levels.     

Effects of neuropeptide Y on insulin and glucagon secretion in the pig.

Neuropeptide Y (NPY)-nerves occur in the pancreas. We therefore infused synthetic porcine NPY directly into the pancreatic artery in anaesthetized pigs to study its direct in vivo influence on pancreatic blood flow and on insulin and glucagon secretion. NPY was given both under basal, normoglycemic conditions, and during an ongoing intravenous infusion of glucose, which raised plasma glucose levels to 20 mM. NPY was infused at 0.5 (n = 2), 5 (n = 3), 35 (n = 7), or 175 (n = 5) pmol/min. We found that NPY at 5, 35, and 175 pmol/min inhibited glucagon secretion. Furthermore, at 35 and 175 pmol/min, NPY also reduced pancreatic blood flow. In contrast, only at 175 pmol/min, NPY inhibited basal and glucose-stimulated insulin secretion. We conclude that in the pig NPY might participate in the regulation of glucagon secretion (as an inhibitor) and of pancreatic blood flow (as a vasoconstrictor). In contrast, NPY does not seem to be involved in the regulation of insulin secretion.