Elevated Amylase and Lipase Levels in Patients Using Glucagonlike Peptide-1 Receptor Agonists or Dipeptidyl-Peptidase-4 Inhibitors In the Outpatient Setting

ObjectiveTo investigate the effects of glucagonlike peptidase-1 (GLP-1) receptor agonists and dipeptidyl-peptidase-4 (DPP-4) inhibitors on serum amylase and serum lipase levels in patients with type 2 diabetes.MethodsIn 90 patients with type 2 diabetes, treatment was initiated with a GLP-1 agonist or a DPP-4 inhibitor. A comparison group consisted of 33 patients with type2 diabetes and similar characteristics who were not prescribed these agents. Baseline serum amylase and lipase levels were measured in all patients and repeated periodically. We determined the percentage of patients with elevated levels of serum amylase or lipase (or both) in both groups.ResultsAmong all 90 patients who received a GLP-1 receptor agonist or a DPP-4 inhibitor, 32 (36%) had an increase in serum amylase or lipase (or both) in comparison with 6 of 33 patients (18%) with such increases in the comparison group. Interestingly, the serum lipase levels increased more than the serum amylase values in all groups. To ascertain that this was not a chance laboratory error, serum samples were submitted to a second independent laboratory, and the same results were obtained. Usually, use of the medication was discontinued when serum lipase or amylase values were found to be elevated at any level.ConclusionBoth GLP-1 receptor agonists and DPP-4 inhibitors are associated with increased levels of serum lipase more than serum amylase in many patients with type2 diabetes, possibly suggesting the presence of pancreatic inflammation. Whether this finding may potentially lead to acute pancreatitis or chronic pancreatitis, as reported in rat models, is currently unknown. Careful observation of patients taking these medications may be prudent. (Endocr Pract. 2012;18:472-477)     

Beneficial Effects of Trypsin Inhibitors Derived from a Spider Venom Peptide in L-Arginine-Induced Severe Acute Pancreatitis in Mice

HWTI is a 55-residue protein isolated from the venom of the spider Ornithoctonus huwena. It is a potent trypsin inhibitor and a moderate voltage-gated potassium channel blocker. Here, we designed and expressed two HWTI mutants, HWTI-mut1 and HWTI-mut2, in which the potassium channel inhibitory activity was reduced while the trypsin inhibitory activity of the wild type form (approximately 5 EPU/mg) was retained. Animal studies showed that these mutants were less toxic than HWTI. The effects of HWTI and HWTI-mut1 were examined in a mouse model of acute pancreatitis induced by intraperitoneal injection of a large dose of L-arginine (4 mg/kg, twice). Serum amylase and serum lipase activities were assessed, and pathological sections of the pancreas were examined. Treatment with HWTI and HWTI-mut1 significantly reduced serum amylase and lipase levels in a dose dependent manner. Compared with the control group, at 4 mg/kg, HWTI significantly reduced serum amylase level by 47% and serum lipase level by 73%, while HWTI-mut1 significantly reduced serum amylase level by 59% and serum lipase level by 72%. Moreover, HWTI and HWTI-mut1 effectively protected the pancreas from acinar cell damage and inflammatory cell infiltration. The trypsin inhibitory potency and lower neurotoxicity of HWTI-mut1 suggest that it could potentially be developed as a drug for the treatment of acute pancreatitis with few side effects.     

Response of exocrine pancreas to corticosterone and aldosterone after adrenalectomy

The long-term effect of adrenalectomy (Adx) on the exocrine pancreas was examined in female adult rats. Pancreatic amylase concentration decrease to 50% of the control level starting 10 days after Adx, whereas the levels of trypsinogen and lipase remained unchanged. Replacement studies beginning 24 h after surgery with corticosterone (B, 1 mg/100 g body wt) or aldosterone (ALDO, 8 micrograms/100 g body wt) alone did not prevent the decline in amylase after Adx. However, when both hormones were administered together, pancreatic amylase concentration was maintained at a level similar to that of the control group. Serum corticosterone levels in the rats receiving B alone or B + ALDO were not different, and were comparable to levels found in normal rats. Both ALDO and B, given for 5 days starting 10 days after Adx, were required to restore amylase concentrations toward control values. When spironolactone (SPIRO, 3 mg/100 g body wt), a specific mineralocorticoid receptor blocker was administered bid together with ALDO + B, it blocked the increase in pancreatic amylase seen in ALDO + B treated rats but did not affect the serum corticosterone levels. These results suggest that mineralocorticoids are also involved in modulating the level of amylase in the rat exocrine pancreas.     

Influence of dietary aflatoxin on certain serum enzyme levels in broiler chickens

Experimental aflatoxicosis was produd in Cobb broiler chickens by feeding them with dietary aflatoxin at concentrations of 1 and 3 ppm for a poriod of four weeks from 0 to 28 days. Twelve birds in triplicate were used for each treatment of which three from each replicate were sacrificed at weekly intervals for enzymatic estimations of SGPT, SGOT, Serum amylase and serum lipase. Thus each treatment contained nine weekly observations and 36 observations in total. The SGPT activity was not found in appreciable amounts either in control or in toxin treated birds. However, the SGOT levels were in measurable amounts and elevated levels were observed in toxin treated birds from first week onwards at both levels of toxin and was dose related. The treatment means of SGOT differed significantly (P<0.05). The serum lipase levels increased from first week onwards and the treatment means showed significant difference (P<0.01). Serum lipase changes in toxin treated birds occurred to about the same extent. But the serum amylase levels decreased from first week onwards and their treatment means differed significantly (P<0.01) at both levels of toxin treated birds. Serum amylase concentrations decreased as the aflatoxin level increased in the diet.Presented in X Annual Poultry Symposium of the Indian Poultry Science Association held at Madras Veterinary College, Madras-600 007, 15th to 17th December, 1983.     

乌司他丁治疗急性胰腺炎的临床疗效及机制研究

目的:探讨乌司他丁对急性胰腺炎患者的临床疗效及可能机制。方法:收集我院收治的重症急性胰腺炎患者66例,随机分为实验组和对照组。所有患者均给予禁食水、充分补液、纠正电解质紊乱等常规支持对症治疗。对照组予奥曲肽,实验组予乌司他丁,共治疗7天。测定两组患者治疗前、后各血清白介素-6(IL-6)、白介素-8(IL-8)及肿瘤坏死因子-α(TNF-α)水平;治疗前、治疗第1、3天及治疗后进行血常规检测,观察白细胞计数(WBC),并进行血淀粉酶(AMS)、尿淀粉酶(UAMY)测定;分别记录两组患者临床症状及体征恢复时间,判定临床疗效。结果:1治疗后,两组患者血清IL-6、IL-8及TNF-α水平均较治疗前显著下降,且实验组较对照组下降更明显(P0.05);2治疗后,两组患者白细胞计数及血、尿淀粉酶水平均较治疗前明显下降,且实验组较对照组下降更明显(P0.05);3治疗后,实验组各项临床症状及体征消失时间均明显短于对照组(P0.05)。结论:乌司他丁可有效改善急性胰腺胰腺炎患者的各项临床症状,这可能与其显著降低其血清IL-6、IL-8、TNF-α、淀粉酶水平、白细胞计数及尿淀粉酶水平有关。     

吲哚美辛联合生长抑素对ERCP术后胰腺炎的预防作用

目的:研究吲哚美辛联合生长抑素对内镜逆行胰胆管造影(ERCP)术后胰腺炎的预防作用及对血清淀粉酶的影响。方法:选取2015年7月至2016年6月在我院行ERCP术的患者共72例,根据随机数字法分为观察和对照组,每组36例。对照组在术前使用生长抑素完成治疗,观察组在此基础上联合吲哚美辛栓剂完成治疗。分析和比较两组患者ERCP术后5、10、24、48h的血清淀粉酶水平,ERCP术后48h胰腺炎的发生率、肝功能变化情况和临床症状改善情况。结果:术前,两组患者血清淀粉酶水平比较无显著差异(P0.05),术后5h,两组患者的血清淀粉酶水平较高,和术后5h相比,两组术后10、24、48h的血清淀粉酶水平明显降低(P0.05),但观察组各时点血清淀粉酶水平均低于对照组(P0.05)。术前,两组患者GGT、ALP、AST水平比较无显著差异(P0.05),术后48h,两组患者GGT、ALP、AST水平较术前无明显变化(P0.05)。术后48 h,观察组的胰腺炎发生率显著低于对照组[8.33%(3/36) vs. 36.11%(13/36)](P0.05)。观察组的皮肤瘙痒、腹泻、恶心、厌食、感染的减轻率均高于对照组(P0.05)。结论:吲哚美辛联合生长抑素能有效降低ERCP术后胰腺炎的发生率,降低血清淀粉酶水平。     

谷氨酰胺对胃大部切除患者血清胃泌素、CA72-4及HIF-1α水平的影响

目的:探究谷氨酰胺对胃大部切除患者术后血清胃泌素、CA72-4及HIF-1α水平影响。方法:收集我院56例胃大部切除术后患者,随机分为实验组和对照组,各28例。对照组给予临床常规营养治疗,实验组在对照组基础上给予丙氨酰谷氨酰胺注射液100 m L/d。治疗结束后,比较两组患者临床疗效血清胃泌素、CA72-4、HIF-1α及VEGF-A水平。结果:对照组患者治疗后临床有效率71.43%低于研究组患者治疗后临床有效率92.86%,具有统计学意义(P0.05);对照组患者复发率35.71%明显高于实验组10.71%,具有统计学意义(P0.05)。治疗后与治疗前相比,患者血清胃泌素、CA72-4、HIF-1α及VEGF-A水平均降低(P0.05);与对照组比较,实验组血清胃泌素、CA72-4、HIF-1α及VEGF-A水平较低(P0.05)。结论:谷氨酰胺能有效提高胃大部切除患者术后的临床疗效,防止复发,推测其机制与降低血清胃泌素、CA72-4、HIF-1α及VEGF-A水平有关。     

高脂血症性与胆源性急性胰腺炎的临床对比分析

目的：对高脂血症性与胆源性急性胰腺炎的临床特点进行对比分析。方法：选取我院2007年1月至2012年1月收治的急性胰腺炎患者81例,按照胰腺炎的发病原因分为高脂血症性胰腺炎（观察组）和胆源性胰腺炎（对照组）。比较两组血清淀粉酶（AMY）、甘油三酯（TG）、脂肪酶（LPS）、尿酸（UA）、丙氨酸转氨酶（ALT）、碱性磷酸酶（AKP）、总胆红素（TBIL）和直接胆红素（DBIL）水平、APACHEII评分、CT严重指数、重症比例、手术比例和6个月复发和死亡率情况的差异。结果：观察组LPS、TG、UA、APACHEII、CT严重指数、重症比例和6月内的复发比例较对照明显升高（P〈0．05或〈0．01）,而ALT、AKP、TBIL、DBIL、AMY水平和手术比例较对照组明显降低（P〈0．01）。结论：与胆源性急性胰腺炎相比,高脂血症性胰腺炎病情更重,复发率和死亡率更高,而血清淀粉酶升高水平低。     

Protective effects of SP600125 a new inhibitor of c-jun N-terminal kinase (JNK) and extracellular-regulated kinase (ERK1/2) in an experimental model of cerulein-induced pancreatitis

Extracellular regulated kinases (ERK1/2) and c-Jun N-terminal Kinases (JNK), are generally considered to play a key role in signal transduction pathways activated by a wide range of stimuli. We studied the effects of SP600125, a novel inhibitor of both JNK and ERK1/2, in male C57/BL6 mice given with an hyper-stimulating dose of cerulein (50 microg/kg for each of four injections at hourly intervals) to elicit secretagogue-induced pancreatitis. A control group received four intra-peritoneal injections of 0.9% saline at hourly intervals. Animals were randomized to receive either SP600125 (15 mg/kg i.p. administered 2 h before and 30 min after the first injection of cerulein) or its vehicle (1 ml/kg of a 10% DMSO/NaCl solution). A group of animals was killed 30 minutes after the last cerulein injection to evaluate pancreatic JNK and ERK1/2 activation by Western Blot analysis. Another group was sacrificed 2 hours after the last cerulein injection to evaluate serum lipase and amylase levels, pancreas oedema, pancreatic content of Tumor Necrosis Factor-alpha (TNF-alpha) and Intercellular adhesion molecule-1 (ICAM-1) and the histological alterations. SP600125 inhibited almost totally JNK activation (90%) and partially ERK1/2 activation (45%), reduced the serum lipase and amylase levels and the degree of oedema, blunted the increased pancreatic content of TNF-alpha and ICAM-1 and protected against the histological damage. Our data confirm that both JNK and ERK1/2 activation plays a key role in acute pancreatitis and that SP600125 may represent a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition.     

Influence of dietary rice culture material containing cyclopiazonic acid on certain serum biochemical parameters of broiler chickens

Three hundred and forty-eight Vencob broiler chickens were fed diets containingPenicillium griseofulvum rice culture material with 0, 12.5, 25 and 50 ppm of the mycotoxin cyclopiazonic acid (CPA) for 28 days. Serum samples were collected from 9 birds in each group at weekly intervals to study the effect of sublethal doses of CPA on certain serum biochemical parameters. Significant reductions in weight gains (p<0.01) and feed consumptions (p<0.05) were observed at 25 and 50 ppm. Exocrine pancreas showed degenerative and necrotic changes in CPA fed chickens. The CPA had significant (p<0.05) influence on serum total protein, albumin, cholesterol, amylase and lipase levels. CPA did not affect serum glucose levels. There was a decline in levels of total serum protein and albumin in CPA fed groups. But serum cholesterol, amylase and lipase showed dose-dependent increases.Paper presented in XI Indian Association of Veterinary Pathologists conference held at Anand, India, Dec 13–15, 1994.     

Response of rat exocrine pancreas to high-fat and high-carbohydrate diets

Intake of diets with high fat content is a risk factor for acute pancreatitis and pancreatic cancer. The underlying mechanisms leading to the development of these diseases due to high fat intake are currently unknown. The current study was designed in rats to determine the physiologic and pathological consequences of a highfat diet that contained excess amounts of cottonseed oil or a high-carbohydrate diet that contained high amounts of sucrose on the exocrine pancreas. Rats were maintained on the diets for 4 weeks, and a cannula was inserted into the right jugular vein and one into the pancreatic duct for collection of pancreatic juice. Volume of the pancreatic juice and concentrations of amylase, lipase, and trypsinogen in the pancreatic juice were measured before and after infusions of CCK-8. Results showed that basal and CCK-stimulated pancreatic outputs of volume, amylase and lipase but not trypsinogen, were significantly elevated in intact rats given a high-fat diet when compared with rats given a high-carbohydrate diet. Forty-eight hours later, rats were sacrificed, and parts of the pancreas were removed for isolation of pancreatic acinar cells and for histopathologic studies. Pancreatic acini isolated from rats on a high-fat diet showed significantly lower basal and CCK-stimulated amylase release when compared with those on a high-carbohydrate diet. Histology of the pancreas of rats on a high-carbohydrate diet appeared normal; however, the pancreas of rats on high-fat diet showed significant alterations in exocrine pancreas. These results showed abnormalities in the exocrine pancreas of rats on a high-fat diet, that were not found in rats on a high-carbohydrate diet; further, they support the contention that a high-fat diet has a deleterious effect on the pancreas.     

Renal handling of amylase and immunoreactive trypsin in pancreatic cancer and chronic pancreatitis.

In order to evaluate the renal metabolism of amylase and immunoreactive trypsin (IRT) in chronic pancreatic disease, we assayed amylase, IRT and creatinine in serum and urine and gamma-glutamyl transferase (GGT) in dialyzed urine as well as alpha-glucosidase (AGL) and ribonuclease (RNase) in 24 control subjects, 34 patients with pancreatic cancer, 52 with chronic pancreatitis and 32 with extra-pancreatic diseases. Urinary amylase and IRT outputs were found to be more elevated in chronic pancreatitis than in control subjects. The levels of serum amylase, its renal inputs and outputs were correlated with the corresponding IRT values. Multiple regression analyses (dependent on amylase or IRT urinary outputs, circulating levels of the two enzymes, creatinine clearance and the excretion of GGT, AGL and RNase predictor variables) showed significant correlations. The standardized partial regression coefficients found to be significant were: GGT, RNase and serum amylase for amylase, and GGT and RNase for IRT. No difference was found between amylase and IRT outputs in patients with chronic pancreatitis, taking the presence or the absence of alcohol abuse, exocrine insufficiency and pancreatic pseudocysts into consideration. Urinary GGT excretion correlated with serum amylase and IRT levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Triacylglycerol metabolism in rat skeletal muscle after exercise

The temporal relationships between triacylglycerol (TG) content and TG lipase activity in slow-twitch (STR) and fast-twitch red (FTR) muscles were determined in rats during recovery from a 2-h swim. Immediately after the exercise, plasma free fatty acid (FFA) was elevated and glycogen concentrations were decreased. TG content was decreased 40% in STR muscle and reduced 45% in FTR muscle. The TG concentration of STR muscle increased in a linear fashion throughout recovery so that control levels were reached within the first 24 h after exercise. TG lipase activity of STR muscle was elevated 36% above control immediately after the swim and continued to increase to 84% above control 24 h after the work. In STR muscle there was a net synthesis of TG, while lipase activity was elevated above that measured in muscle of control rats. TG content of FTR muscle remained 45% below control throughout the first 24 h of recovery, and TG lipase activity increased from 26% (P greater than 0.05) greater than control immediately after exercise to threefold above control 24 h after work. All parameters returned to control levels by 48 h of recovery. These data indicated that a net TG synthesis occurs in STR muscle when lipolytic activity is elevated. In FTR muscle, however, a gradual increase in TG lipase activity that occurs during the first 24 h of recovery accompanies a TG concentration well below the control level throughout this same time frame.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormone, inorganic phosphate concentrations and enzyme activity in hemodialyzed and kidney-transplanted children

Several serum hormone concentrations, enzyme activities, and inorganic phosphate complexes were investigated in 13 hemodialyzed children, 7 kidney-transplanted children, and in 15 healthy controls. Prior to kidney transplantation 10 of the 14 tested hormone levels of hemodialyzed children differed significantly from those of healthy controls; however, after kidney transplantation most of them normalized, only the angiotensin-converting enzyme and alkaline phosphatase activities were significantly elevated in comparison with the control group. Among the different inorganic phosphate complexes, dialysis had the least effect on the CaHPO4 complex. In the hemodialyzed group the plasma renin activities were decreased and the amylase and lipase activities were increased.     

Effects of gabexate mesilate on serum inflammatory cytokines in rats with acute necrotizing pancreatitis

Gabexate mesilate is a synthetic protease inhibitor. The effectiveness of gabexate mesilate in patients with acute pancreatitis is controversial. Proinflammatory cytokines are associated with systemic inflammatory response syndrome (SIRS) in acute pancreatitis. A compensatory anti-inflammatory response occurs in parallel with SIRS. We investigated the effects of gabexate mesilate on acute necrotizing pancreatitis in rats, emphasizing the changes in serum levels of proinflammatory and anti-inflammatory cytokines. Acute necrotizing pancreatitis was induced by retrograde infusion of sodium taurodeoxycholate into the pancreatobiliary duct in rats. The rats were divided into three groups. Group I was given gabexate mesilate 2 mg/kg/h i.v. continuously 1 h before the induction of acute pancreatitis. Group II was given gabexate mesilate the same dose immediately after the induction of acute pancreatitis. Group III was given normal saline as the controls. Serum levels of amylase, lipase, tumor necrosis factor alpha, interleukin-6, and interleukin-10, pancreatic histopathology and hemodynamics were examined at 5h after the induction of acute pancreatitis. Gabexate mesilate significantly reduced serum levels of amylase, lipase, tumor necrosis factor alpha and interleukin-6 at 5 h. Serum levels of interleukin-10 significantly increased in Group I, as compared with Groups II and III. The severity of pancreatic histopathology, the reduction of mean arterial pressure, the volume of ascites and pancreatic wet weight/body weight ratios were also significantly improved by the administration of gabexate mesilate. The beneficial effects of gabexate mesilate on acute pancreatitis may be, in part, due to the modulation of inflammatory cytokine responses.     

Stimulatory effects of human pancreatic polypeptide on rat pancreatic acini

The effect of human pancreatic polypeptide (HPP) on rat pancreatic acini has been studied. It was found that HPP stimulated amylase and lipase release from the acini. The secretory response of acini to HPP was dose-dependent in a sigmoidal fashion. Between 10(-9) M and 10(-8) M concentration of HPP there was a slow increase of enzyme release to about 40-60% over basal release. At concentrations of HPP above 10(-8) M there was a rapid increase of enzyme release, amounting to 4-6 times over basal release at 10(-6) M concentration of HPP. The potency of HPP compared to other secretagogues at 10(-7) M concentration was 45% of CCK, 60% of carbachol and 75% of secretin. HPP did not inhibit the effect of CCK, secretin and carbachol on amylase release. The amylase release stimulated by HPP was accompanied by an increase in 45Ca2+ efflux. Atropine or dibutyryl cyclic GMP did not influence the effect of HPP. It is concluded that HPP stimulates the release of enzymes from rat pancreatic acini and that Ca2+ may be a mediator for this secretion.     

Control of the release of digestive enzymes in the larvae of the fall armyworm,Spodoptera frugiperda

There is a basal level of enzyme activity for trypsin, aminopeptidase, amylase, and lipase in the gut of unfed larval (L6) Spodoptera frugiperda. Trypsin activity does not decrease with non‐feeding, possibly because of the low protein levels in plants along with high amino acid requirements for growth and storage (for later reproduction in adults). Therefore, trypsin must always be present so that only a minimal protein loss via egestion occurs. Larvae, however, adjust amylase activity to carbohydrate ingestion, and indeed amylase activity is five‐fold higher in fed larvae compared to unfed larvae. Gut lipase activity is low, typical of insects with a high carbohydrate diet. A flat‐sheet preparation of the ventriculus was used to measure the release of enzymes in response to specific nutrients and known brain/gut hormones in S. frugiperda. Sugars greatly increase (>300%) amylase release, but starch has no effect. Proteins and amino acids have little or no effect on trypsin or aminopeptidase release. The control of enzyme release in response to food is likely mediated through neurohormones. Indeed, an allatostatin (Spofr‐AS A5) inhibits amylase and trypsin, and allatotropin (Manse‐ AT) stimulates amylase and trypsin release. Spofr‐AS A5 also inhibits ileum myoactivity and Manse‐AT stimulates myoactivity. The epithelial secretion rate of amylase and trypsin was about 20% of the amount of enzyme present in the ventricular lumen, which, considering the efficient counter‐current recycling of enzymes, suggests that the secretion rate is adequate to replace egested enzymes. © 2009 Wiley Periodicals, Inc.     

Glycosidically bound sialic acid levels as a predictive marker of postoperative adjuvant therapy in gastric cancer

Summary A group of 293 gastric cancer patients were examined to see if the preoperative value of glycosidically bound sialic acid is a predictor of prognosis and effectiveness of postoperative adjuvant therapy. All patients had gastrectomies and were histologically confirmed to have primary adenocarcinoma of the stomach. Some patients then received either postoperative adjuvant chemotherapy or immunochemotherapy. Patients with sialic acid levels less than 74.5 mg/dl survived significantly longer than those with sialic acid levels of 74.5 mg/dl or of 85.3 mg/dl and over. No significant differences in survival were found among patients treated by gastrectomy alone, gastrectomy plus chemotherapy and gastrectomy plus immunochemotherapy. However, patients with abnormally elevated levels of sialic acid survived significantly longer when they were treated with immunochemotherapy after gastrectomy than those treated by gastrectomy alone or with chemotherapy after gastrectomy. By using Cox's multivariate regression model, pTNM stages, postoperative adjuvant therapy (chemotherapy and immunochemotherapy) and preoperative serum levels of sialic acid were examined as prognostic variables. Postoperative therapy was a significant prognostic variable in patients with abnormally elevated levels of sialic acid. The preoperative serum level of sialic acid is a promising predictive marker of the response to postoperative adjuvant immunochemotherapy.     

Changes in mRNA levels of rat pancreatic lipase in the early days of consumption of a high-lipid diet

The time-course response of rat pancreatic enzymes to a diet containing 25% sunflower oil was investigated. A 1.2-fold enhancement in lipase specific activity was observed as early as the first day of diet consumption and was further increased up to 1.9-fold on the 5th day. On the other hand, colipase activity was slightly decreased during the first two days of high-lipid diet intake and then increased. An immediate and direct effect was also exerted by the 25% lipid diet on lipase biosynthesis. Both fractional synthetic rate and specific activity of lipase were comparably induced. Due to a 1.6-fold increase in the overall protein synthesis following 5 days of lipid diet consumption, the absolute synthesis of lipase and amylase was increased by 3.5-fold and 0.98-fold, respectively, as compared to control animals. By contrast, the synthesis of procarboxypeptidases and serine proteases did not increase before day 5, probably as the result of a distinct adaptive mechanism. The pancreatic mRNA levels in control and adapted animals, which were determined by dot-blot hybridization with amylase and lipase cDNAs, were consistent with a biphasic induction of lipase synthesis since a first increase in the level of the enzyme-specific mRNA during the first two days of diet intake (4-fold on day 1) was followed by a second increase after the fourth day (6.5-fold on day 5). On the other hand, amylase mRNA level was unchanged during the dietary manipulation. Thus, hyperlipidic diets exerted an both lipase activity and synthesis but a delayed effect on procarboxypeptidase and serine protease synthesis. In a similar manner, the immediate induction of lipase mRNA level by dietary fat, followed by another increase a few days later, suggested that at least two different mechanisms are involved in lipase mRNA induction.