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Inhibitory effect of rat amylin on the insulin responses to glucose and arginine in the perfused rat pancreas 总被引:4,自引:0,他引:4
Amylin, a 37-amino acid polypeptide, is the main component of amyloid deposits in the islets of Langerhans, and has been identified in the B-cell secretory granules. We have investigated the effect of rat amylin on the insulin and glucagon release by the isolated, perfused rat pancreas. Amylin infusion at 750 nM, markedly reduced unstimulated insulin release (ca. 50%, P less than 0.025), whereas it did not modify glucagon output. At the same concentration, amylin also blocked the insulin response to 9 mM glucose (ca. 80%, P less than 0.025) without affecting the suppressor effect of glucose on glucagon release. The inhibitory effect of amylin on glucose-induced insulin secretion was confirmed by lowering the amylin concentration (500 nM) and increasing the glucose stimulus (11 mM); again, no effect of amylin on glucagon release was observed. Finally, amylin, at 500 nM, reduced the insulin response to 3.5 mM arginine (ca. 40%, P less than 0.025) without modifying the secretion of glucagon elicited by this amino acid. It can be concluded that, in the rat pancreas, the inhibitory effect of homologous amylin on unstimulated insulin secretion, as well as on the insulin responses to metabolic substrates (glucose and arginine), favours the concept of this novel peptide as a potential diabetogenic agent. 相似文献
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Effect of age on the insulin secretory response of perfused rat pancreas to arginine and tolbutamide
In this study we compared the ability of perfused pancreases from 2 1/2 month-old and 12 month-old rats to secrete insulin in response to arginine or tolbutamide. The results indicate that the insulin secretory response to either secretagogue was between 25-85% greater (two-way analysis of variance, P less than .01) by perfused pancreases of older rats. On the other hand, islet cell mass was approximately three-fold greater in the pancreases of the older rats. When this difference in mass of insulin secretory tissue was taken into consideration, it became apparent that insulin secretion per beta cell by perfused pancreases of the older rats was only half that of the younger rats in response to either arginine or tolbutamide (two-way analysis of variance, P less than 0.001). Thus, the decline with age in the ability of the beta cell to secrete insulin, previously noted in response to glucose, involves other insulin secretagogues as well. 相似文献
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The ventral and the dorsal parts of the rat pancreas were perfused separately via either the superior mesenteric artery (0.6 ml/min) or the coeliac artery (1.4 ml/min). Control perfusions were performed via both arteries (2 ml/min). Expressed relative to the weight of tissue, the insulin content was comparable in the ventral and dorsal parts whereas the glucagon content was 2.5 times lower in the ventral than dorsal part. In comparison to the dorsal or total pancreas, the insulin secretory activity of the ventral pancreas was markedly decreased in response to either an elevation of the glucose concentration or the administration of carbamylcholine or arginine. The difference between the ventral and dorsal response was less marked at low glucose concentrations (3.3 or 7.0 mmol/l) and, possibly, in response to glucagon. In the case of glucagon release, a decreased response of the ventral pancreas was only observed when glucagon output was fully stimulated by the administration of arginine at a low glucose concentration. These results indicate that the B cell in the ventral pancreas responds poorly to several stimuli. There was little evidence to support the involvement of endogenous glucagon in the diminished sensitivity of the ventral B cells. 相似文献
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The effects of glucagon-like peptide 1 (7-36) amide [GLP-1 (7-36) amide] and glucagon on the release of islet amyloid polypeptide (IAPP), or amylin, from the isolated perfused rat pancreas were studied. In the presence of 5.6 mM glucose, GLP-1 (7-36) amide and glucagon stimulated the release of amylin from the perfused pancreas. The infusion of GLP-1 (7-36) amide at a concentration of 10(-9) M elicited a biphasic release of amylin similar to that of insulin. The cumulative output of amylin induced by 10(-9)M GLP-1 (7-36) amide was significantly higher than that by 10(-9)M glucagon (p less than 0.01). The amylin/insulin molar ratios induced by GLP-1 (7-36) amide and glucagon were about 1% and did not differ significantly. These findings suggest that GLP-1 (7-36) amide and glucagon stimulate the release of amylin from the pancreas and that the concomitant secretion of amylin and insulin might contribute to glucose homeostasis. 相似文献
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Cosecretion of amylin and insulin from isolated rat pancreas 总被引:2,自引:0,他引:2
Amylin, a 37 amino acid C-terminal amidated peptide is an integral part of secretory granules of pancreatic beta-cells. Utilizing a specific radioimmunoassay system we demonstrate in the present study a cosecretion of amylin and insulin from the isolated rat pancreas. The secretion pattern of both peptides during glucose or glucose plus arginine stimulation is identical. The molar ratio of amylin amounts to 10% of that of insulin. The biological significance of amylin is still unknown, but a paracrine/endocrine role in glucose homeostasis is speculated. 相似文献
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Behaviorally specific inhibition of sham feeding by amylin 总被引:1,自引:0,他引:1
To further characterize amylin’s inhibitory action on feeding, we examined the effects of intraperitoneal injections of amylin on sham feeding of sucrose in food-deprived male rats with chronic gastric cannulas. Thirty and 100 μg/kg amylin reduced sham feeding, but did not terminate it or elicit the behavioral sequence of satiety. Real feeding of sucrose, but not sham feeding, was reduced after injection of 10 μg/kg amylin. Amylin’s inhibitory effect on sham feeding appeared behaviorally specific because neither 30 nor 100 μg/kg amylin affected sham drinking of water in thirsty rats and because no abnormal behaviors occurred. We conclude that amylin has a behaviorally specific satiating effect on sucrose sham feeding that is insufficient to elicit satiety in absence of gastric or postgastric food stimulation. 相似文献
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In order to study the oeffect of somatostatin on the endocrine pancreas directly, islets isolated from rat pancreas by collagenase were incubated for 2 hrs 1) at 50 and 200 mg/100 ml glucose in the absence and presence of somatostatin (1, 10 and 100 mg/ml) and2) at 200 mg/100 ml glucose together with glucagon (5 mug/ml), with or without somatostatin (100 ng/ml). Immunologically measurable insulin was determined in the incubation media at 0, 1 and 2 hrs. Insulin release was not statistically affected by any concentration stomatostatin. On the other hand, somatostatin exerted a significant inhibitory action on glucagon-potentiated insulin secretion (mean +/- SEM, mu1/2 hrs/10 islets: glucose and glucagon: 1253 +/- 92; glucose, glucagon and somatostatin: 786 +/- 76). The insulin output in th epresence of glucose, glucagon and somatostatin was also significantly smaller than in thepresence of glucose alone (1104 +/- 126) or of glucose and somatostatin (1061 +/- 122). The failure of somatostatin to affect glucose-stimulated release of insulin from isolated islets contrasts its inhibitory action on insulin secretion as observed in the isolated perfused pancreas and in vivo. This discrepancy might be ascribed to the isolation procedure using collagenase. However, somatostatin inhibited glucagon-potentiated insulin secretion in isolated islets which resulted in even lower insulin levels than obtained in the parallel experiments without glucagon. It is concluded that the hormone of the alpha cells, or the cyclic AMP system, might play a part in the machanism of somatostatin-induced inhibition of insulin release from the beta-cell. 相似文献
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Plasma glucagon, insulin and glucose responses to intravenous arginine infusion in the rat 总被引:1,自引:0,他引:1
S F Kuku J B Jaspan D S Emmanouel A I Katz A H Rubenstein 《Hormones et métabolisme》1978,10(2):99-100
Plasma glucagon (IRG), insulin and glucose responses to intravenous arginine infusion in the rat were studied. Three doses of arginine hydrochloride were infused into fasted rats: 0.2 gm/kg b.w., 0.5 gm/kg b.w., and 1 gm/kg b.w. The 0.2 gm/kg dose did not result in significant elevation of plasma IRG or insulin. Both the 0.5 and 1 gm/kg doses produced a significant increase in glucagon and insulin levels within 5 minutes of starting the infusion. The 1 gm/kg dose was most effective in stimulating secretion of both hormones. This dose produced a 250% rise in the plasma IRG compared to 80% peak rise with the 0.5 gm/kg dose (p less than .01) and 1055% rise in insulin levels compared to a peak level of 225% above baseline with the 0.5 gm/kg dose (p less than .001). These results demonstrate the effectiveness of intravenous arginine in the stimulation of glucagon and insulin secretion in the rat. 相似文献
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Benthem L Mundinger TO Taborsky GJ 《American journal of physiology. Endocrinology and metabolism》2001,280(2):E378-E381
The present study tested the hypothesis that activation of the parasympathetic nervous system could attenuate sympathetic activation to the pancreas. To test this hypothesis, we measured pancreatic norepinephrine (NE) spillover (PNESO) in anesthetized dogs during bilateral thoracic sympathetic nerve stimulation (SNS; 8 Hz, 1 ms, 10 mA, 10 min) with and without (randomized design) simultaneous bilateral cervical vagal nerve stimulation (VNS; 8 Hz, 1 ms, 10 mA, 10 min). During SNS alone, PNESO increased from the baseline of 431 +/- 88 pg/min to an average of 5,137 +/- 1,075 pg/min (P < 0.05) over the stimulation period. Simultaneous SNS and VNS resulted in a significantly (P < 0.01) decreased PNESO response [from 411 +/- 61 to an average of 2,760 +/- 1,005 pg/min (P < 0.05) over the stimulation period], compared with SNS alone. Arterial NE levels increased during SNS alone from 130 +/- 11 to approximately 600 pg/ml (P < 0.05); simultaneous SNS and VNS produced a significantly (P < 0.05) smaller response (142 +/- 17 to 330 pg/ml). Muscarinic blockade could not prevent the effect of VNS from reducing the increase in PNESO or arterial NE in response to SNS. It is concluded that parasympathetic neural activity opposes sympathetic neural activity not only at the level of the islet but also at the level of the nerves. This neural inhibition is not mediated via muscarinic mechanisms. 相似文献
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Cyclooxygenase (COX) is the key enzyme for prostaglandin (PG) synthesis. PGs are mediators of many critical physiological and inflammatory responses. There are two isoforms, COX-1 and COX-2, both of which are constitutively expressed in the central nervous system (CNS). Studies have shown that COX-1 and COX-2 are involved in physiological and pathological conditions of the brain. However, little is known about the role(s) of COX in the host defense system against a viral infection in the CNS. In this report, we used Vesicular Stomatitis Virus (VSV) induced acute encephalitis to distinguish between the contribution(s) of the two isoforms. COX-2 activity was inhibited with a COX-2 selective drug, celecoxib (Celebrex), and COX-1 was antagonized with SC560. We found that inhibition of COX-2 led to decreased viral titers, while COX-1 antagonism did not have the same effect at day 1 post infection. 5-lipooxygenase (5-LO) expression and neutrophil recruitment in the CNS were increased in celecoxib-inhibited mice. Furthermore, mice treated with celecoxib expressed more Nitric Oxide Synthase-1 (NOS-1), a crucial component of the innate immune system in the restriction of VSV propagation. The expression of type 1 cytokines, IFN-gamma and IL-12, were also increased in celecoxib-treated mice. 相似文献
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The biosynthesis of glucagon in perfused rat pancreas 总被引:4,自引:3,他引:1
The biosynthesis of glucagon was studied by using the recirculated, isolated perfused rat pancreas. [3H]Tryptophan was initially incorporated into acid–ethanol-extractable protein, which on gel filtration was eluted with a molecular weight of about 9000 and contained a small amount of glucagon immunoreactivity. With longer incubation [3H]tryptophan incorporation into a second peak was obtained in an identical position with that of the majority of rat glucagon immunoreactivity. This peak of labelled protein exhibited migration characteristics on polyacrylamide-gel electrophoresis identical with those of rat glucagon and was identified as newly synthesized glucagon by demonstration of specific binding and dissociation behaviour with glucagon antibodies. The incorporation of [3H]tryptophan into acid–ethanol-extractable protein was inhibited by cycloheximide. High concentrations of glucose increased [3H]tryptophan incorporation into high-molecular-weight protein but decreased incorporation into proteins smaller than cytochrome c. The pattern of [3H]leucine incorporation into protein was similar to that of [3H]tryptophan. 相似文献