Effect of suppression of endocrine or exocrine pancreatic function in hemorrhagic shock.

Somatostatin did not influence the pathologic consequences of hemorrhagic shock, but pancreatic duct ligation prevented the post-oligemic decline of arterial pressure and formation of toxic factors. These results indicate that pancreatic acinar cells release myocardial depressant factor and are important in the pathophysiology of shock.     

Effect of long acting somatostatin-analogue, SMS 201 995, on gut hormone secretion in normal subjects

SMS 201 995 is a new long acting analogue of somatostatin. We have investigated its effect on basal and meal stimulated secretion of gut hormones and have shown that after a single s.c. injection of 50 micrograms it lowers significantly the basal plasma levels of pancreatic polypeptide, secretin, motilin, pancreatic glucagon and insulin, it also effectively suppresses the postprandial release of pancreatic polypeptide, gastrin, secretin, gastric inhibitory peptide, pancreatic glucagon and insulin. Except for the usual brief discomfort of an injection, no symptoms or untoward effects were observed.     

Evidence of an ileal hormone inhibiting pancreatic secretion (ACP anticholecystokinine peptide)]

The contact of long and medium chain fatty acids with the ileal mucosa inhibits basal or stimulated pancreatic protein secretion of Man, Dog, Cat and Rat. This inhibition is due to an inhibitory factor transmitted by cross-circulation. We isolated from partially purified extracts of Pig ileum a peptide which inhibits strongly volume and protein pancreatic output of the conscious Rat. We propose to call this factor ACP, anticholecystokinine peptide.     

Effect of long acting somatostatin-analogue,SMS 201995, on gut hormone secretion in normal subjects

Summary SMS 201 995 is a new long acting analogue of somatostatin. We have investigated its effect on basal and meal stimulated secretion of gut hormones and have shown that after a single s. c. injection of 50 g it lowers significantly the basal plasma levels of pancreatic polypeptide, secretin, motilin, pancreatic glucagon and insulin, it also effectively suppresses the postprandial release of pancreatic polypeptide, gastrin, secretin, gastric inhibitory peptide, pancreatic glucagon and insulin. Except for the usual brief discomfort of an injection, no symptoms or untoward effects were observed.     

The islet-acinar axis of the pancreas: Is there a role for glucagon or a glucagon-like peptide?

Intravenous glucagon inhibits exocrine pancreatic secretion in vivo, but exogenous glucagon does not affect exocrine secretion in vitro. Recent work, however, suggested that endogenous glucagon may be involved in the regulation of exocrine secretion even in vitro. We therefore investigated the effects of exogenous and endogenous glucagon on exocrine secretion by the isolated perfused rat pancreas in the presence of 1.8 mM glucose. Exogenous glucagon did not affect CCK-stimulated amylase output. 20 mM arginine stimulated glucagon release, but did not affect basal enzyme secretion. CCK-stimulated amylase output, however, was significantly inhibited in the presence of arginine. This inhibitory effect of arginine on exocrine pancreatic secretion could be blocked by glucagon antibodies, but not by nonspecific gammaglobulins. Thus exogenous glucagon failed to affect exocrine pancreatic secretion in vitro, but endogenously released glucagon or a glucagon-like peptide inhibited amylase release in the isolated perfused pancreas. We conclude that glucagon or a glucagon-like peptide may be a mediator in the islet-acinar axis.     

饮用咖啡与胰腺癌患病的Meta分析

目的 综合评价饮用咖啡因素与胰腺癌发生的相关性,进一步探讨胰腺癌的危险因素.方法 检索1970.01.01/2010.10.01国内外公开发表的有关人群饮用咖啡和胰腺癌发生的病例对照研究,制定纳入标准,采用Rev Man4.2软件对研究资料进行Meta分析,定量综合评价饮用咖啡与胰腺癌的关系.结果 共有15组病例-对照研究符合入选标准,累积胰腺癌病例共3 335例和正常对照者共15 064例.Meta分析显示,合并OR=1.08(95％ CI:0.88～1.31),(P=0.48),差异无统计学意义；男性组结果显示,OR和95％ CI为1.14(0.95-1.37),差距不具有统计学意义(P=0.15),女性组结果显示OR和95％CI为1.18(0.98-1.43),(P=0.09),由于P＜0.1,故属于边缘性显著差异.结论 女性胰腺癌患者中有饮用咖啡习惯与无饮用咖啡习惯的人相比,饮用咖啡的习惯可能会增加胰腺癌的发病风险.     

Impaired insulin release in aging rats: Metabolic and ionic events

We investigated the effect of aging on glucose uptake, glucose-induced O₂ consumption, glucose-induced⁴⁵Ca movements, and calmodulin content to elucidate age-related impairment of glucose-induced insulin release in pancreatic islets of Wistar rats. Intact pancreatic islets from old (24-month-old) rats showed impaired glucose-induced insulin release; glucose uptake and O₂ consumption were lower in old than in young (2-month-old) or adult (12-month-old) rats. Moreover,⁴⁵Ca uptake and calmodulin content were decreased in pancreatic islets from older rats, which explained the impairment in glucose-induced insulin release in aging. No major differences between the 3 age groups in glucose-induced⁴⁵Ca efflux in pancreatic islets were observed.     

Bombesin-like immunoreactivity in the pancreas of man and other mammalian species

Summary Bombesin-like immunoreactivity has been measured in pancreatic tissues of man (12.4±1.2 pmol/g), pig (15.8±3.2), calf (4.3±0.9), rat (8.5±1.2) and guinea-pig (2.8±0.6) by a specific radioimmunoassay. Gel filtration of the pancreatic extracts revealed 2 major immunoreactive peaks: the earlier peak was eluted in the position of porcine gastrin-releasing peptide, and the later peak was eluted just after the amphibian bombesin standard. Immunocytochemistry demonstrated the presence of bombesin-like immunoreactivity in nerves in the rat pancreas, particularly in the exocrine pancreas, and occasionally in the peri-insular spaces. Isolated rat pancreatic islets were found to contain small quantities of bombesin-like immunoreactivity (0.037±0.003 fmol/islet) suggesting that mammalian bombesin-like peptides may be invovled in the regulation of endocrine as well as exocrine pancreatic secretion.Acknowledgments. We are grateful to Dr. A. V. Edwards, Physiological Laboratory, Cambridge, U. K. for providing the calf tissues, and the British Diabetic Association, U. K. for support.To whom reprint requests should be addressed.     

The glucose dependence of pancreatic endocrine responses to 2-deoxyglucose in the calf

Summary The initial plasma glucose concentration of unanesthetized calves with cut splanchnic nerves, given 2-deoxyglucose (1.2 mmoles/kg, i.v.), was either lowered by prior starvation, or raised by a continuous infusion of exogenous glucose. Raising the initial plasma glucose concentration completely suppressed the release of pancreatic glucagon and pancreatic polypeptide but substantially enhanced the release of insulin in response to 2-deoxyglucose.This work has been supported by the Medical Research Council and the Leverhulme Trust. We are also indebted to Mr P.M.M. Bircham and Mr G.P. Macgregor for their skilled technical assistance.     

Heat shock response in the central nervous system

The heat shock response is induced in nervous tissue in a variety of clinically significant experimental models including ischemic brain injury (stroke), trauma, thermal stress and status epilepticus. Excessive excitatory neurotransmission or the inability to metabolically support normal levels of excitatory neurotransmission may contribute to neuronal death in the nervous system in many of the same pathophysiologic circumstances. We demonstrated that in vitro glutamate-neurotransmitter induced excitotoxicity is attenuated by the prior induction of the heat shock response. A short thermal stress induced a pattern of protein synthesis characteristic of the highly conserved heat shock response and increased the expression of heat shock protein (HSP) mRNA. Protein synthesis was necessary for the neuroprotective effect. The study of the mechanisms of heat shock mediated protection may lead to important clues as to the basic mechanisms underlying the molecular actions of the HSP and the factors important for excitotoxic neuronal injury. The clinical relevance of these findings in vitro is suggested by experiments performed by others in vivo demonstrating that pretreatment of animals with a submaximal thermal or ischemis stress confers protection from a subsequent ischemic insult.     

Factors influencing the intestinal phase of pancreatic exocrine secretion in the turkey

The present study was done to investigate the factors regulating the intestinal phase of exocrine pancreatic secretion in the turkey. The intestine of turkeys equipped with pancreatic fistulas was perfused with peptone solution, fat emulsion and hydrochloric acid (HCl), and pancreatic flow and protein output were measured. Neither peptone solution nor fat emulsion had any effects on pancreatic secretion. HCl enhanced the flow rate of pancreatic juice but not protein output. To clarify the neural mechanism of this phenomenon, the vagal postganglionic blocker atropine was continuously infused and pancreatic secretion in response to intestinal HCl was measured. Atropine completely suppressed both pancreatic flow and protein output. It is suggested that the avian intestinal phase of pancreatic secretion is mainly controlled by cholinergic action though HCl stimulation.     

Acute effects of adrenergic agents on post-defibrillation arrest time in a cultured heart model

Possible drug interactions with electrical defibrillation were examined. We tested the hypothesis that adrenergic agents (epinephrine, norepinephrine, isoproterenol) and a calcium channel blocker (verapamil), when applied acutely, alter the duration of arrest following a defibrillator shock. A secondary hypothesis (based on observations) was that the drugs alter the occurrence of changes to normal rhythms following the shock. Dissociated heart cells from 10-day chicken embryos were cultured to form spherical aggregates and plated in petri dishes. In the experiments, the spheres were paced at 0.75 V/cm above contraction threshold, and a biphasic defibrillator shock was applied for 1 ms at 46 V/cm. The arrest time and occurrence of rhythm changes were recorded. The adrenergic agents shortened the duration of arrest following a defibrillator shock, while the calcium channel blocker lengthened the arrest time. Comparisons with the control proportion of double beats showed no significant change with the adrenergic agents and a decrease with verapamil.Received 19 August 2004; received after revision 8 October 2004; accepted 18 October 2004     

New evidence on the robust identification of news shocks: Role of revisions in utilization‐adjusted TFP series and term structure data

Data revisions and selections of appropriate forwarding‐looking variables have a major impact on true identification of news shocks and quality of research findings derived from structural vector autoregression (SVAR) estimation. This paper revisits news shocks to identify the role of different vintages of total factor productivity (TFP) series and term structure of interest rates as major prognosticators of future economic growth. There is a growing strand of literature regarding the use of utilization‐adjusted TFP series, provided by Fernald (Federal Reserve Bank of San Francisco, Working Paper Series, 2014) for identification of news shocks. We reestimate Barsky and Sims' (Journal of Monetary Economics, 2011, 58, 273–289) empirical analysis by employing 2007 and 2015 vintages of TFP data. We find substantial quantitative as well as qualitative differences among impulse response functions when using 2007 and 2015 vintages of TFP data. Output and hours initially decline, followed by quick reversal of both variables. In sharp contrast to results achieved by the 2007 vintage of TFP data, results achieved by the 2015 vintage of TFP data depict that output and hours will increase in response to positive TFP shock. By including term structure data in our VAR specification, total surprise technology shock and news shock account for 97% and 92% of the forecast error variance in total TFP and total output respectively. We find that revisions in TFP series over time ultimately impact the conclusion regarding news shocks on business cycles. Our results support the notion that term structure data help in better identification of news shock as compared to other forward‐looking variables.     

Pancreatic polypeptide: A possible role in the regulation of food intake in the mouse. Hypothesis

Summary Pancreatic polypeptide (PP) is a recently identified hormone produced by pancreatic endocrine cells. The islets of genetically obese mice (ob/ob, C57 BL/6J), which are suspected to lack a circulating satiety factor, contain relatively few of the PP-producing cells. Administration of bovine pancreatic polypeptide (bPP) reduces food intake and suppresses body weight gain in the hyperphagic obese mice. It is postulated that PP participates in the regulation of food intake in a manner as yet undefined.This work was supported by grant No. 3.553.75 from Swiss National Science Foundation. We thank Mrs M. Eissler and Mr R. Cuche for their valuable help.     

Effect of pancreatic duct ligation on exocrine pancreatic function and structure in the rabbit

4 weeks after pancreatic duct ligation in the rabbit, fecal and luminal chymotrypsin were detected in concentrations similar to the control group. Pancreatic changes in the ligated group were marked dilatation of the main pancreatic duct, proliferation and distention of ductules and fibrosis. Despite pancreatic duct ligation and fibrosis, proteolytic enzymes continued to secrete into the duodenal lumen. These results suggest that pancreatic duct ligation in the rabbit is not associated with total pancreatic insufficiency.     

A convulsant, 3-mercaptopropionic acid,decreases the level of GABA and GAD in rat pancreatic islets and brain

To investigate the properties of the gamma-aminobutyric acid (GABA) synthesizing enzyme, glutamate decarboxylase (GAD), in the brain and the pancreatic islets of the rat, GABA concentration in the brain and the pancreatic islets was measured after intraperitoneal administration of 3-mercaptopropionic acid (3-MP) at 25 mg/kg. 60 min after the administration of 3-MP, GABA concentration in the hypothalamus, the superior colliculus and the hippocampus of the brain decreased by 20–30% and in the pancreatic islets by 35%. The concentration in the pancreatic acini did not change. Western blotting showed that GAD activity in the pancreatic islets decreased after administration of 3-MP compared to the control. The activity of GAD in the pancreatic islets as well as brain can be modified by a convulsant, in this case 3-MP. These results suggest the properties of GAD may be similar in the pancreatic islets and brain.     

Proteolytic inactivation of human leukocyte elastase

Human leukocyte elastase can be proteolytically inactivated by bovine pancreatic trypsin. Neither porcine pancreatic elastase nor bovine pancreatic chymotrypsin causes inactivation of leukocyte elastase, nor are trypsin, pancreatic elastase, or chymotrypsin themselves susceptible to proteolysis. The trypsin-catalyzed inactivation of leukocyte elastase can be slowed by inhibition of trypsin with benzamidine or by occupation of elastase's active site with elastatinal.     

Glucagon and pancreatic polypeptide immunoreactivities co-exist in a population of rat islet cells

In mammalian pancreas, glucagon and pancreatic polypeptide have been shown to be present in distinct cell types. The present communication reports that, in rat pancreas, in addition to glucagon and pancreatic polypeptide cell populations, there is a small population of cells which contain both glucagon and pancreatic polypeptide immunoreactivities.