Animal Models Of Pancreatitis Research Articles

MODELS OF CHRONIC PANCREATITIS

Laboratory models of acute and chronic pancreatitis in animals are created in order to study the mechanisms of pathogenesis, develop new methods of treatment and carcinogenesis during inflammation of the pancreas. Both in vitro models are used to study the early stage, short-term processes in which acinar cells are involved, as well as models that cause the development of mild or severe forms of the disease in rodents. Although rodents are most commonly used in models of pancreatitis, the pancreatic damage they cause does not necessarily fully correspond to human pathology. Therefore, it is necessary to carefully choose the model most suitable for the answer in this particular task. The purpose of this article is to compare the most widely used animal models of pancreatitis.

Incretin based therapy and pancreatic cancer: Realising the reality.

Incretin-based therapies like glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors help maintain the glycaemic control in patients with type 2 diabetes mellitus with additional systemic benefits and little risk of hypoglycaemia. These medications are associated with low-grade chronic pancreatitis in animal models inconsistently. The incidence of acute pancreatitis was also reported in some human studies. This inflammation provides fertile ground for developing pancreatic carcinoma (PC). Although the data from clinical trials and population-based studies have established safety regarding PC, the pathophysiological possibility that low-grade chronic pancreatitis leads to PC remains. We review the existing literature and describe the relationship between incretin-based therapies and PC.

Novel mitochondrial transition pore inhibitor N-methyl-4-isoleucine cyclosporin is a new therapeutic option in acute pancreatitis.

•Bile acids, ethanol and fatty acids affect pancreatic ductal fluid and bicarbonate secretion via mitochondrial damage, ATP depletion and calcium overload. •Pancreatitis-inducing factors open the membrane transition pore (mPTP) channel via cyclophilin D activation in acinar cells, causing calcium overload and cell death; genetic or pharmacological inhibition of mPTP improves the outcome of acute pancreatitis in animal models. •Here we show that genetic and pharmacological inhibition of mPTP protects mitochondrial homeostasis and cell function evoked by pancreatitis-inducing factors in pancreatic ductal cells. •The results also show that the novel cyclosporin A derivative NIM811 protects mitochondrial function in acinar and ductal cells, and it preserves bicarbonate transport mechanisms in pancreatic ductal cells. •We found that NIM811 is highly effective in different experimental pancreatitis models and has no side-effects. NIM811 is a highly suitable compound to be tested in clinical trials. Mitochondrial dysfunction plays a crucial role in the development of acute pancreatitis (AP); however, no compound is currently available with clinically acceptable effectiveness and safety. In this study, we investigated the effects of a novel mitochondrial transition pore inhibitor, N-methyl-4-isoleucine cyclosporin (NIM811), in AP. Pancreatic ductal and acinar cells were isolated by enzymatic digestion from Bl/6 mice. In vitro measurements were performed by confocal microscopy and microfluorometry. Preventative effects of pharmacological [cylosporin A (2µm), NIM811 (2µm)] or genetic (Ppif-/- /Cyp D KO) inhibition of the mitochondrial transition pore (mPTP) during the administration of either bile acids (BA) or ethanol+fatty acids (EtOH+FA) were examined. Toxicity of mPTP inhibition was investigated by detecting apoptosis and necrosis. In vivo effects of the most promising compound, NIM811 (5 or 10mgkg-1 per os), were checked in three different AP models induced by either caerulein (10×50µgkg-1 ), EtOH+FA (1.75gkg-1 ethanol and 750mgkg-1 palmitic acid) or 4% taurocholic acid (2mlkg-1 ). Both genetic and pharmacological inhibition of Cyp D significantly prevented the toxic effects of BA and EtOH+FA by restoring mitochondrial membrane potential (Δψ) and preventing the loss of mitochondrial mass. In vivo experiments revealed that per os administration of NIM811 has a protective effect in AP by reducing oedema, necrosis, leukocyte infiltration and serum amylase level in AP models. Administration of NIM811 had no toxic effects. The novel mitochondrial transition pore inhibitor NIM811 thus seems to be an exceptionally good candidate compound for clinical trials in AP.

Covering the Cover

Covering the Cover

Measuring Autophagy in Pancreatitis.

Acute pancreatitis is one of the first pathological processes where autophagy has been described in a human tissue. Autophagy, autodigestion, and cell death are early cellular events in acute pancreatitis. Recent advances in understanding autophagy highlight its importance in pathological conditions. However, methods for monitoring autophagic activity during complex diseases, involving highly differentiated secretory cells, are complicated, and the results are sometimes misinterpreted. Here, we describe methods used to identify autophagic structures and to measure autophagic flux in cultured cell models and animal models of pancreatitis. We also briefly describe the pancreas specific autophagy mouse model that was useful to understand the actual role of autophagy in pancreatitis and to identify a novel selective autophagy pathway named zymophagy. Lastly, we describe the immunomagnetic isolation of autophagosomes and the detection of autophagy in pancreatic tissue samples derived from humans.

Tu1371 - Hydromorphone Worsens the Severity of Acute Pancreatitis in Animal Model of the Disease

Tu1371 - Hydromorphone Worsens the Severity of Acute Pancreatitis in Animal Model of the Disease

Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal Models

Little is known about the signaling pathways that initiate and promote acute pancreatitis (AP). The pathogenesis of AP has been associated with abnormal increases in cytosolic Ca2+, mitochondrial dysfunction, impaired autophagy, and endoplasmic reticulum (ER) stress. We analyzed the mechanisms of these dysfunctions and their relationships, and how these contribute to development of AP in mice and rats. Pancreatitis was induced in C57BL/6J mice (control) and mice deficient in peptidylprolyl isomerase D (cyclophilin D, encoded by Ppid) by administration of L-arginine (also in rats), caerulein, bile acid, or an AP-inducing diet. Parameters of pancreatitis, mitochondrial function, autophagy, ER stress, and lipid metabolism were measured in pancreatic tissue, acinar cells, and isolated mitochondria. Some mice with AP were given trehalose to enhance autophagic efficiency. Human pancreatitis tissues were analyzed by immunofluorescence. Mitochondrial dysfunction in pancreas of mice with AP was induced by either mitochondrial Ca2+ overload or through a Ca2+ overload-independent pathway that involved reduced activity of ATP synthase (80%inhibition in pancreatic mitochondria isolated from rats or mice given L-arginine). Both pathways were mediated by cyclophilin D and led to mitochondrial depolarization and fragmentation. Mitochondrial dysfunction caused pancreatic ER stress, impaired autophagy, and deregulation of lipid metabolism. These pathologic responses were abrogated in cyclophilin D-knockout mice. Administration of trehalose largely prevented trypsinogen activation, necrosis, and other parameters of pancreatic injury in mice with L-arginine AP. Tissues from patients with pancreatitis had markers of mitochondrial damage and impaired autophagy, compared with normal pancreas. In different animal models, we find a central role for mitochondrial dysfunction, and for impaired autophagy as its principal downstream effector, in development of AP. In particular, the pathway involving enhanced interaction of cyclophilin D with ATP synthase mediates L-arginine-induced pancreatitis, a model of severe AP the pathogenesis of which has remained unknown. Strategies to restore mitochondrial and/or autophagic function might be developed for treatment of AP.

Quantitative ultrasound and the pancreas

Pancreatitis is inflammation of the pancreas. Cerulein-induced pancreatitis in animal models can cause a significant increase in pancreatic enzymes in blood, as well as interstitial edema and inflammatory cell infiltration in the pancreas. This degree of pancreatitis is mild; all animals survive the induction of pancreatitis and resolves within ~6 days after induction, making this an excellent model to study the attenuation coefficient (AC: dB/cm-MHz) and backscatter coefficient (BSC: 1/cm-sr) of the pancreas temporally. The edematous stroma and shrinkage and dedifferentiation of acinar cells, has certain similarities with the morphology in some forms of pancreatic carcinoma. The pancreas’ AC and BSC (20-50 MHz) were estimated in vivo and ex vivo at baseline (before cerulein injections) and at 24 h, 48 h and 72 h after cerulein injections in Sprague-Dawley rats (N = 24). AC and BSC showed the same trends whereby (relative to baseline values) the 24-h AC decreased ~0.3 dB/cm-MHz and BSC decreased ~1-2 dB w...

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis.

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere.

Immune cells and immune-based therapy in pancreatitis

Alcohol and gallstones are the most common etiologic factors in acute pancreatitis (AP). Recurrent AP can lead to chronic pancreatitis (CP). Although the underlying pathophysiology of the disease is complex, immune cells are critical in the pathogenesis of pancreatitis and determining disease severity. In this review, we discuss the role of innate and adaptive immune cells in both AP and CP, potential immune-based therapeutic targets, and animal models used to understand our knowledge of the disease. The relative difficulty of obtaining human pancreatic tissue during pancreatitis makes animal models necessary. Animal models of pancreatitis have been generated to understand disease pathogenesis, test therapeutic interventions, and investigate immune responses. Although current animal models do not recapitulate all aspects of human disease, until better models can be developed available models are useful in addressing key research questions. Differences between experimental and clinical pancreatitis need consideration, and when therapies are tested, models with established disease ought to be included.

Antioxidative phytoceuticals to ameliorate pancreatitis in animal models: an answer from nature.

Despite enthusiastic efforts directed at elucidating critical underlying mechanisms towards the identification of novel therapeutic targets for severe acute pancreatitis (SAP), the disease remains without a specific therapy to be executed within the first hours to days after onset of symptoms. Although earlier management for SAP should aim to either treat organ failure or reduce infectious complications, the current standard of care for the general management of AP in the first hours to days after onset of symptoms include intravenous fluid replacement, nutritional changes, and the use of analgesics with a close monitoring of vital signs. Furthermore, repeated evaluation of severity is very important, as the condition is particularly unstable in the early stages. In cases where biliary pancreatitis is accompanied by acute cholangitis or in cases where biliary stasis is suspected, an early endoscopic retrograde cholangiopancreatography is recommended. However, practice guidelines regarding the treatment of pancreatitis are suboptimal. In chronic pancreatitis, conservative management strategies include lifestyle modifications and dietary changes followed by analgesics and pancreatic enzyme supplementation. Recently, attention has been focused on phytoceuticals or antioxidants as agents that could surpass the limitations associated with currently available therapies. Because oxidative stress has been shown to play an important role in the pathogenesis of pancreatitis, antioxidants alone or combined with conventional therapy may improve oxidative-stress-induced organ damage. Interest in phytoceuticals stems from their potential use as simple, accurate tools for pancreatitis prognostication that could replace older and more tedious methods. Therefore, the use of antioxidative nutrition or phytoceuticals may represent a new direction for clinical research in pancreatitis. In this review article, recent advances in the understanding of the pathogenesis of pancreatitis are discussed and the paradigm shift underway to develop phytoceuticals and antioxidants to treat it is introduced. Despite the promise of studies evaluating the effects of antioxidants/phytoceuticals in pancreatitis, translation to the clinic has thus far been disappointing. However, it is expected that continued research will provide solid evidence to justify the use of antioxidative phytoceuticals in the treatment of pancreatitis.

Antarease-like Zn-metalloproteases are ubiquitous in the venom of different scorpion genera

BackgroundThe venoms of several scorpion species have long been associated with pancreatitis in animal models and humans. Antarease, a Zn-metalloprotease from Tityus serrulatus, is able to penetrate intact pancreatic tissue and disrupts the normal vesicular traffic necessary for secretion, so it could play a relevant role in the onset of acute pancreatitis. MethodsThe cDNA libraries from five different scorpion species were screened for antarease homologs with specific primers. The amplified PCR products were cloned and sequenced. A structural model was constructed to assess the functionality of the putative metalloproteases. A phylogenetic analysis was performed to identify clustering patterns of these venom components. ResultsAntarease-like sequences were amplified from all the screened cDNA libraries. The complete sequence of the antarease from T. serrulatus was obtained. The structural model of the putative antarease from Tityus trivittatus shows that it may adopt a catalytically active conformation, sharing relevant structural elements with previously reported metalloproteases of the ADAM family. The phylogenetic analysis reveals that the reported sequences cluster in groups that correlate with the geographical localization of the respective species. ConclusionsAntareases are ubiquitous to a broad range of scorpion species, where they could be catalytically active enzymes. These molecules can be used to describe the evolution of scorpion venoms under different ecogeographic constrains. General significanceFor the first time the complete sequence of the antareases is reported. It is demonstrated that antareases are common in the venom of different scorpion species. They are now proposed as targets for antivenom therapies.

A Review of Animal Models of Nonneoplastic Pancreatic Diseases

The nonneoplastic diseases of the human pancreas generally comprise the inflammatory and degenerative conditions that include acute and chronic pancreatitis, with cystic fibrosis being arguably one of the most important diseases that induce the condition. Both acute and chronic conditions vary in severity, but both can be life threatening; and because of this fact, the study of their progression, and their responsiveness to therapy, is largely conducted by indirect means using serum markers of damage and repair such as amylase and lipase activities that normally occur at very low levels in the circulation but can be significantly increased during inflammatory episodes. Progress in the understanding the pathogenesis of both conditions has therefore been largely due to time course studies in animal models of pancreatitis, and it is in this context that animal model development has been so significant. In general terms, the animal models can be divided into the invasive, surgical procedures, and those induced by the administration of chemical secretagogues that induce hypersecretion of the pancreatic enzymes. The former include ligation and/or cannulation of the biliopancreatic ducts with infusion of solutions of various kinds, or the formation of closed duodenal loops. Secretagogue administration includes administration of caerulein or l-arginine in various protocols. An additional model involves administration of dibutyltin dichloride, which induces a partial blockage of the pancreatic ducts to induce pancreatic disease through enzymic reflux into the gland. The models have been invaluable in generating testable hypotheses for the human diseases. These hypotheses for the production of cellular damage as the initiating events in the disease include (1) intracellular chemical activation, (2) pancreatic secretion reflux, (3) intracellular production of reactive oxygen species, and (4) intracellular production of free radicals.

Animal models of pancreatitis: Can it be translated to human pain study?

Chronic pancreatitis affects many individuals around the world, and the study of the underlying mechanisms leading to better treatment possibilities are important tasks. Therefore, animal models are needed to illustrate the basic study of pancreatitis. Recently, animal models of acute and chronic pancreatitis have been thoroughly reviewed, but few reviews address the important aspect on the translation of animal studies to human studies. It is well known that pancreatitis is associated with epigastric pain, but the understanding regarding to mechanisms and appropriate treatment of this pain is still unclear. Using animal models to study pancreatitis associated visceral pain is difficult, however, these types of models are a unique way to reveal the mechanisms behind pancreatitis associated visceral pain. In this review, the animal models of acute, chronic and un-common pancreatitis are briefly outlined and animal models related to pancreatitis associated visceral pain are also addressed.

Novel targets and regulatory ordeal by QT interval

Platelet-activating factor (PAF), also known as PAF-acether and AGEPC (acetyl-glyceryl-ether-phosphorylcholine), is a lipid-derived biological messenger active at subnanomolar concentrations [1]. ‘PAF’ is something of a misnomer as it acts on a variety of cells, not only on platelets, with possible roles in allergy and inflammation as well as haemostasis/ thrombosis. PAF is made from acyl-PAF in a two-step process summarized in Figure 1: a highlyregulated cytosolic enzyme phospholipase A2 (PLA2) acts on acyl-PAF to produce lyso-PAF, which is then acetylated to give PAF. PLA2 simultaneously liberates free arachidonic acid from the 2-position of glycerol in cell membranes initiating the production of eicosanoids (prostaglandins, leukotrienes, and lipoxins) in parallel with PAF. PAF is inactivated by deacetylation which regenerates the inactive lyso-PAF precursor. PAF is produced by activated inflammatory cells and acts via specific G-protein-coupled PAF-receptors. Injected subcutaneously it produces many of the signs and symptoms of inflammation, including vasodilatation and redness, increased vascular permeability and wheal formation, and, at higher concentrations, hyperalgesia. It is a potent chemotaxin for neutrophils and monocytes, and recruits eosinophils into the bronchial mucosa in the late phase of asthma. It can itself activate PLA2, reinforcing eicosanoid synthesis by positive feedback. It has spasmogenic effects on both bronchial and ileal smooth muscle and stimulates arachidonate turnover and TXA2 generation by platelets, producing shape change and releasing platelet granule contents. The PAF pathway (of biosynthesis, receptors, and downstream transduction events) is thus an attractive therapeutic target, but it is not yet clear whether inhibiting it will prove therapeutically advantageous in thrombotic or inflammatory diseases.There was great excitement following the discovery of PAF (by Jacques Benveniste, a French immunologist) in the early 1970s, but sadly no drugs have really made it to market. However, the anti-inflammatory actions of the glucocorticoids may partly be caused by inhibition of PAF synthesis [2], so we should not give up hope. Competitive antagonists of PAF and/or specific inhibitors of lyso-PAF acetyltransferase could well be useful anti-inflammatory and/or anti-asthmatic drugs. The PAF antagonist lexipafant is effective in a rat model of acute pancreatitis [3], but several small human studies have been negative or inconclusive. Icatibant, an antagonist at bradykinin B2 receptors, was also effective in animal models of pancreatitis but not in the human disease.It has since been licensed in Europe for use in hereditary angiooedema in patients with C1-esterase deficiency, exemplifying how difficult it can be to find the optimum match between an inhibitor or antagonist of a mediator and disease target: one of many challenges for translational medicine [4]. The same message is provided by a complement inhibitor, eculizumab, also recently licensed in Europe for the rare and previously almost completely untreatable disease paroxysmal nocturnal haemoglobinuria – see articles in our new drugs’ mechanisms feature [5, 6]. Rupatidine is a combined H1 and PAF antagonist [7], licensed in several parts of the world for treating allergic rhinitis and for chronic urticaria, but it is not clear what (if anything) its action on PAF receptors adds to its therapeutic efficacy over and above its antihistamine action [8].The withdrawal from the market of another less-sedating antihistamine, terfenadine, ushered in the modern era of regulatory concern over cardiac safety of non-cardiac drugs. Astemizole, also a less-sedating antihistamine, had similar effects and was also withdrawn, raising the spectre of a drug-class effect. This has not proved to be the case: many non-cardiac drugs with quite different primary pharmacology have been implicated [9] and several antihistamines British Journal of Clinical Pharmacology DOI:10.1111/j.1365-2125.2010.03657.x

A Novel Biosensor for Evaluation of Apoptotic or Necrotic Effects of Nitrogen Dioxide during Acute Pancreatitis in Rat

The direct and accurate estimation of nitric dioxide levels is an extremely laborious and technically demanding procedure in the molecular diagnostics of inflammatory processes. The aim of this work is to demonstrate that a stop-flow technique utilizing a specific spectroscopic biosensor can be used for detection of nanomolar quantities of NO2 in biological milieu. The use of novel compound cis-[Cr(C2O4)(AaraNH2)(OH2)2]+ increases NO2 estimation accuracy by slowing down the rate of NO2 uptake. In this study, an animal model of pancreatitis, where nitrosative stress is induced by either 3g/kg bw or 1.5 g/kg bw dose of l-arginine, was used. Biochemical parameters and morphological characteristics of acute pancreatitis were monitored, specifically assessing pancreatic acinar cell death mode, NO2 generation and cellular glutathione level. The severity of the process correlated positively with NO2 levels in pancreatic acinar cell cytosol samples, and negatively with cellular glutathione levels.

Efficacy of Recombinant Human Interleukin-10 in Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in Subjects With Increased Risk

Pancreatitis is the most common major complication of endoscopic retrograde cholangiopancreatography (ERCP). Inflammatory cytokines are released during acute pancreatitis. Interleukin-10 (IL-10) is a potent inhibitor of cytokines and has been shown to attenuate pancreatitis in animal models and pilot human studies. This study aimed to determine whether prophylactic IL-10 administration reduces the frequency and/or severity of post-ERCP pancreatitis in high-risk patients. A randomized, multicenter, double-blind, placebo-controlled study was conducted. Patients received IL-10 at a dose of either 8 or 20 microg/kg or placebo as a single intravenous injection 15 to 30 minutes before ERCP. Standardized criteria were used to diagnose and grade the severity of postprocedure pancreatitis. A total of 305 of the planned total enrollment of 948 patients were randomized. There was a 15%, 22%, and 14% incidence of post-ERCP pancreatitis in the IL-10 (8 microg/kg), IL-10 (20 microg/kg), and placebo treatment groups, respectively (P = 0.83 for IL-10 8 microg/kg vs placebo and 0.14 for IL-10 20 microg/kg vs placebo). Due to apparent lack of efficacy, the study was terminated at an interim analysis. : There was no apparent benefit of IL-10 treatment when compared with placebo in reducing the incidence of post-ERCP acute pancreatitis in subjects with increased risk.

Angiotensin-converting enzyme gene DD genotype neither increases susceptibility to acute pancreatitis nor influences disease severity

BackgroundThe renin-angiotensin system (RAS) has been implied in the pathogenesis of various diseases including acute and chronic pancreatitis. Angiotensin-converting enzyme (ACE) is the key enzyme in activating the RAS. Deletion (D)-type polymorphism in the 16th intron of the ACE gene has been associated with higher serum levels of the enzyme. Inhibition of ACE was found to ameliorate acute pancreatitis in animal models suggesting that ACE plays a role in pathogenesis and progression of acute pancreatitis. Objectives were to investigate the occurrence of the ACE insertion/deletion (I/D) polymorphism in acute pancreatitis patients and its association with the severity of the disease. Material and MethodsSeventy-nine acute pancreatitis patients and 95 healthy controls were evaluated. Acute pancreatitis cases were grouped as mild or severe according to the Atlanta criteria. Main outcome measure: The presence of the ACE I/D polymorphism. ResultsACE gene I and D allele frequency of patients (44% and 56%) were similar to controls (45% and 55%, respectively). There were no significant differences in severity of pancreatitis between patients with the ACE-insertion or ACE-insertion/deletion versus ACE-deletion genotypes. ConclusionsThe ACE gene deletion polymorphism is neither a risk factor for development of acute pancreatitis nor contributes to the severity of disease or development of complications.

Protective role of angiotensin II type 2 receptor signaling in a mouse model of pancreatic fibrosis

The renin-angiotensin system contributes to pathological processes in a variety of organs. In the pancreas, blocking the angiotensin II (AII) type 1 receptor (AT1) attenuates pancreatic fibrogenesis in animal models of pancreatitis. Because the role of the AII type 2 receptor (AT2) in modulating pancreatic injury is unknown we investigated the role of AT2 in pancreatic injury and fibrosis. Pancreatic fibrosis was induced by repetitive cerulein administration in C57BL/6 wild-type (WT) or AT2-deficient (AT2-/-) mice and assessed by morphology and gene expression at 10 days. There was no difference between WT and AT2-/- mice in the degree of acute pancreatic injury as assessed by amylase release at 9 and 12 h and by histological examination of the pancreas at 12 h. In contrast, parenchymal atrophy and fibrosis were more pronounced in AT2-/- mice compared with WT mice at 10 days. Fibrosis was accompanied by activation of pancreatic stellate cells (PSC) evaluated by Western blot analysis for alpha-smooth muscle actin and by immunocytochemistry; PSC activation was further increased in AT2-/- mice compared with WT mice. The level of pancreatic transforming growth factor-beta1 mRNA and protein after repetitive cerulein treatment was higher in AT2-/- mice than in WT mice. Our results demonstrate that, in contrast to AT1 receptor signaling, AT2 receptor signaling modulates protective antifibrogenic effects in a mouse model of cerulein-induced pancreatic fibrogenesis. We propose that the effects of AII on injury-induced pancreatic fibrosis may be determined by the balance between AT1 and AT2 receptor signaling.

Acute Experimental Pancreatitis in Rats Is Ameliorated by Treatment with Pramlintide, a Synthetic Analogue of the β-Cell Hormone Amylin

Purpose: Acute pancreatitis is a common and major complication of endoscopic retrograde cholangiopancreatography (ERCP) and limits the use of this otherwise safe procedure. Antisecretory drugs such as somatostatin (SST) and its long-acting analogue octreotide, or protease inhibitors such as gabexate mesilate, have been tested as therapies for pharmacological prevention of post-ERCP pancreatitis, but uncertainty still exists over their clinical benefit. At physiologically relevant doses in animal models, the β-cell hormone amylin slows gastric emptying, inhibits gastric acid secretion and exocrine pancreatic secretion, and protects the gastric mucosa. The present study examined the effect of pramlintide (pram), a synthetic human amylin analogue, on prevention of caerulein-induced acute pancreatitis in anesthetized Sprague Dawley®TM (SD) rats. Methods: Saline, pram (300 μg/kg/h), SST (10 μg/kg bolus) or pram+SST in combination (N = 16, 5, 5, 6, respectively) was infused intravenously from 30 min before until 240 min after caerulein IP injection (10 μg/kg) into fasted, male, anesthetized SD rats (320–360 g). As an index of acute pancreatitis, plasma lipase and amylase were measured for up to 240 minutes after caerulein injection. Results: Following caerulein injection, plasma amylase increased 2.23-fold at 240 min in saline-treated controls compared to 1.40-, 1.61- and 1.51-fold in rats receiving pram, SST or the combination (P < 0.01, P < 0.04 and P < 0.01, respectively). Plasma lipase increased by 20.3-fold in the control saline group compared to 8.1-, 6.1- and 5.0-fold in pram, SST or combination groups (P < 0.02, P < 0.01 and P < 0.01, respectively). Although each was different from controls, there were no significant differences between SST, pram or pram+SST treatments in attenuating caerulein-induced increases in plasma amylase and lipase in this animal model of pancreatitis. Conclusion: Pramlintide ameliorated increases in pancreatic enzyme activity in this rat model of acute pancreatitis. Future studies are warranted to explore the potential use of pramlintide in the prevention of pancreatitis, which may occur during ERCP procedures. This research was funded in part by Amylin Pharmaceuticals, Inc., San Diego, CA.