Amylase Excretion Research Articles

Approach to Hyperamylasemia and Hyperlipasemia

Hyperamylasemia and hyperlipidemia occur when the amounts of amylase and lipase that enter the blood overweigh the kidney and liver reticuloendothelial system clearance of the enzymes. In normal homeostasis, most of these enzymes are excreted from the apical membrane of the acinar cells into the ductal system of the gland. However, in pathological conditions, this apical exocytosis is blocked, and the leakage of these enzymes at the basolateral membrane is increased. Therefore, these enzymes are released into the bloodstream. Many different pancreatic pathologies and Gullo syndrome can cause this type of leakage in the pancreas. This mechanism can also cause basolateral leakage in other organs that secrete amylase and lipase. In small bowel inflammatory conditions, amylase and lipase are absorbed through the inflamed mucosa and introduced into the bloodstream due to increased vascular permeability. Regardless of the enzymes that enter the blood circulation, several kidney and liver diseases prevent the excretion and metabolism of serum amylase and lipase. When the amylase and lipase are combined with immunoglobulins, they escape normal glomerular filtration due to the development of macroenzymes and accumulate in the blood. These situations related to the clearance of the enzymes are also crucial mechanisms of serum enzyme elevation that should not be overlooked.

Secrets, puzzles and mysteries of macroamylasemia

Physiological features of amylase synthesis and excretion are considered in the article, presence of other sources of amylase synthesis different from pancreas and salivary glands is emphasized. Definitions of hyperenzymemia and macroamylasemia (MAE) are given. MAE is a state characterized by presence of circulating complexes of normal serum amylase with protein or carbohydrates in blood. There are 3 types of MAE: first — classical (constant hyperamylasemia, decreased amylase level in urine, high blood concentration of macroamylase complexes); second — hyperamylasemia with slightly decreased amylase activity in urine, macroamylase/normal amylase ratio is less than in the first type; third — normal blood and urine amylase activity, low macroamylase/normal amylase ratio. Pathogenesis is explained by connection of blood amylase and acute phase protein in different inflammatory, infectious diseases, malabsorption. MAE clinical manifestations could be absent, sometimes abdominal pain is possible. Hyperamylasemia and reduced urine amylase activity are typical. MAE diagnostics means determination of macroamylase complexes in blood (chromatography, calculation of the clearance ratio of amylase and creatinine). The article presents clinical cases describing extra-pancreatic MAE in women with malignant ovarian lesions. The question of expediency of thorough diagnostic examination in asymptomatic MAE is raised, which may turn out to be a symptom of cancer. The lack of specific treatment for MAE is emphasized.

Association between Amylase Excretion Fraction and Acute Renal Transplant Rejection in Pediatrics

Association between Amylase Excretion Fraction and Acute Renal Transplant Rejection in Pediatrics

반응표면분석법을 통한 Arthrobacter sp.의 amylase 생산 최적화

In this study, the physical factors for amylase production by Arthrobacter sp. were optimized using response surface methodology(RSM). Antarctic microorganism Arthrobacter sp. PAMC 27388 was obtained from the Polar and Alpine Microbial Collection(PAMC) at the Korea Polar Research Institute. This microorganism was confirmed for the excretion of amylase with Lugol`s solution. The amylase activity was after flask culture was as low as 1.66 mU/L before optimization. The physical factors including the inoculum volume, the initial culture pH, and the medium volume were chosen to be optimized for the enhanced amylase production. The calculated results using RSM indicate that the optimal physical factors were 2.49 mL inoculum volume, 6.85 pH and 42.87 mL medium volume with a predicted amylase production of 2.84 mU/L. The experimentally obtained amylase activity was 2.50 mU/L, which was a 150% increase compared to the level before optimization.

Evidence for “gibberellin-like” activity of coumarin

The existing body of information defines some regulatory functions to secondary metabolites like coumarin (COU). Experience and some experimental results in our laboratory tempted us to test a GA-like activity of COU. Experiments were conducted with endospermic (de-embryonated) and embryonic wheat half grains treated with different concentrations of COU, for different time courses, alone or in combination with the GA-biosynthesis inhibitor paclobutrazol (P). Results showed that treatment with COU caused stimulation of amylase synthesis and secretion from aleurone layer cells. P did not affect synthesis but slightly reduced excretion of amylase. However, germination percentage of intact wheat grains and seedling growth were inhibited by COU in a concentration-dependent manner. This indicates that COU has some GA-like effect, and also affects other aspects of germination and seedling establishment. This GA-like effect was also confirmed by the observed increase in elongation of wheat seedlings second leaf sheath and pea stem when treated with COU. These potential regulatory roles of COU may indicate that secondary metabolites have more important roles during different plant developmental processes.

Serum fetuin-A and recurrent urolithiasis in young adults

Recurrence of urolithiasis is frequent. There are no reliable markers able to indicate recurrent stone former patients. Fetuin-A inhibits hydroxyapatite crystals formation and expansion. This study aims at evaluating whether serum fetuin-A may predict recurrent urolithiasis in young adults. This is a multicentre study. Young adults patients with recurrent urolithiasis attending 3 urology clinics were enrolled from July 2011 to December 2012. Inclusion criteria were: age 18-40 years, presence of more than one kidney stone. Exclusion criteria were: diabetes mellitus, metabolic disorders, obesity, hypertension, cardiovascular disease, infection diseases. Controls were participants without history of urolithiasis and currently undetected stones. Routine biochemistry, serum concentration of oxalate, fetuin-A, and parathyroid hormone (PTH) were assessed; 24/h urinary excretion of creatinine, uric acid, calcium, sodium, phosphorus, potassium, magnesium, glucose, oxalate, amylase, and protein was measured. Kidney ultrasonography and plain X-ray examination was performed. The total cohort was represented by 120 young adults participants (90 patients, and 30 controls). Clinical characteristics were not different between patients and controls. No significant differences were found in serum concentrations as well as in 24/h urinary excretion of recorded variables. No significant difference was found in serum concentration of fetuin-A (median 35.1 ± 18.62 SD Vs 35.12 ± 14.12, μg/ml; p = 0,908). The data of present study do not substantiate the hypothesis that serum fetuin-A may be a reliable predictor of recurrent urolithiasis in young adults.

Drosophila melanogaster larvae control amylase secretion according to the hardness of food

Drosophila melanogaster larvae excrete amylase and perform external digestion of their food. In this study, to investigate whether their external digestion ability varies in response to changes in the external environment, we measured the relative amount of amylase excreted by larvae using a new method: the iodine starch agar method (ISAM). Analysis using this method revealed that the amount of amylase excreted by larvae increased in accordance with the increase in the agar concentration. In addition, we investigated the effect on the larval growth rate of adding amylase to the diet. Pupation occurred 24 h later in food containing 1% amylase than in food containing no amylase. These results suggest that the larvae adjust their amylase excretion in response to changes in the external environment, and that its level has a marked influence on the larval growth rate.

膵における Amylase 合成と分泌動態に関する研究

膵における Amylase 合成と分泌動態に関する研究

Trasplante combinado reno-pancreático

A 42-year-woman with a history of juvenile-onset diabetes mellitus was referred to University Hospitals of Cleveland for pancreas transplantation. Diabetes was first diagnosed at age 15, and insulin therapy was begun at that time. At the time of her referral, her serum creatinine concentration was 1.4 mg/dl and the creatinine clearance 80 ml/min. Protein excretion was 1.2 g/24 hrs. Diabetic retinopathy, discovered four years earlier, had been treated with laser surgery. A cadaveric pancreatic transplant was performed using pancreaticoduodenocystotomy. The patient’s postoperative course was complicated by a peripancreatic abscess that required surgical drainage on two occasions. The patient was euglycemic and insulin-independent until one month following surgery, when overt hyperglycemia and a relative decrease in urinary amylase excretion prompted a 10-day course of treatment with OKT3 for presumed acute allograft rejection. Her blood sugar level returned to the normal range; five months later, however, a second rejection episode did not respond to treatment with OKT3. The patient’s pancreatic allograft was surgically removed and insulin therapy was renewed. During the subsequent 18 months, the patient developed peripheral vascular disease requiring a right transmetatarsal amputation; this was followed by a right, below-the-knee amputation. During this interval, the patient’s renal function gradually deteriorated, in part because of two episodes of contrast-medium-induced nephropathy following aortography. She developed end-stage renal disease requiring initiation of maintenance hemodialysis. Two years following the initial pancreatic transplant, the patient received simultaneous kidney and pancreas transplants from one cadaveric donor. Maintenance immunosuppression consisted of cyclosporine, prednisone, and azathioprine. One month following transplantation, the patient was treated with OKT3 for acute renal allograft rejection. Thereafter, she maintained excellent renal allograft function. Glycohemoglobin levels, which had ranged between 8.5% and 9.3% during the six months prior to transplantation, decreased to 4.3% within two months of transplantation. Visual acuity measured within two months after the transplant procedure was 20/300 OD and 20/200 OS. In the seven years following combined kidney-pancreas transplantation, the patient was readmitted to the hospital on 12 occasions. Three separate hospital admissions were prompted by gross hematuria. Cystoscopic evaluation revealed only acute and chronic inflammation of the bladder mucosa and duodenal cuff. Recurrent hematuria prompted enteric conversion of the pancreatic allograft via a pancreaticojejunostomy approximately six years following transplanation. Two years later, the patient developed gangrene of the left foot, which required a left Syme’s amputation. Five years following kidney-pancreas transplantation, the patient published an autobiography detailing how the transplant had improved her quality of life. At last followup, her serum creatinine concentration was 1.1 mg/dl; glycohemoglobin was 3.8%. Visual acuity was 20/30 OD and 20/25 OS.

Sex-related differences in effect of ethanol administration and folic acid supplementation on pancreatic amylase in rats.

The present study was designed to determine whether folic acid supplement is sufficient to reverse the negative effects of ethanol consumption on amylase activity during gestation, lactation, and growth. Moreover, this study investigated the sex-related differences in amylase content in the pancreatic tissue, serum, and urine. The animals were randomized into three groups: Control group (CG) received water and a basic rat diet during pregnancy, lactation, and growth; Ethanol-rats (EG) were fed an ethanol diet during pregnancy, the suckling period, and growth until death; and Ethanol + folic acid group (E + FG) were handled the same way as those of EG, except they received a folic acid supplement from reproduction until the end of experimental period. Our results showed that ethanol consumption decreased the pancreatic amylase level in offspring rats at 2 months postpartum. Folic acid supplementation did not alter pancreatic amylase activities. In offspring males, ethanol administration decreased serum amylase activity at 2 months postpartum. Folic acid supplementation in males resulted in higher serum amylase levels than those corresponding to the ethanol-fed group. In females, no significant differences between groups in serum amylase levels were found. Ethanol consumption decreased urinary amylase excretion (at 30 days and 2 months postpartum), but the folic acid-supplemented group showed a more pronounced decrease in urine amylase activity than in the ethanol-fed group. At 30 days postpartum, no sex difference in urinary amylase was identified. However, in general, males showed higher values for urine amylase than females at 2 months postpartum. A folic acid-supplemented diet exerts an advantageous effect on amylase in serum in offspring males at 2 months postpartum of mothers fed ethanol during gestation and lactation periods, because amylase renal absorption is increased. In offspring females, amylase renal absorption is also increased, but we did not observed an advantageous effect on amylase in serum. It may be that sexual differentiation in females at 2 months postpartum exerts a definitive effect on amylase in serum. We found a sex-related difference in amylase activities; therefore, we suggest that in future all results of the exocrine pancreas function, in male and female animals, be analyzed separately.

Postoperative oral glucose tolerance and stimulated insulin secretion: a predictor of endocrine graft function more than 10 years after pancreas-kidney transplantation.

After pancreas transplantation, endocrine function is determined by the insulin secretory capacity of the transplanted pancreas. The authors evaluated the predictive value of postoperative oral glucose tolerance test (OGTT) and stimulated insulin secretion on long-term endocrine function. Forty-one patients after pancreas-kidney transplantation with systemic venous drainage were studied. Patients were categorized to have normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) (World Health Organization criteria: NGT, <7.8 mM; IGT, 7.8-11.1 mM 120 min after glucose intake) and high or low total insulin secretion. Mean follow-up of graft function and patient outcome was 10.2+/-0.5 years after OGTT. Patients with IGT had grafts with a longer ischemia time and a significantly worse urine amylase excretion as compared with patients with NGT. Using Kaplan-Meier survival analysis, patients with NGT had better long-term pancreatic function as compared with IGT in the follow-up after performing the first OGTT (mean, 10.9+/-0.2 vs. 8.8+/-0.9 years of graft function; P=0.02), but there was no difference in patient survival and kidney graft function. Also, high insulin secretion predicted significantly longer pancreas graft function as compared with low insulin secretion (P=0.04). Although IGT does not lead to poorer long-term patient survival and kidney graft function, it does predict compromised long-term endocrine function of the transplanted pancreas. Therefore, postoperative OGTT are useful tools for identification of patients at risk of long-term endocrine graft failure after pancreas transplantation.

Low serum amylase levels in drinking alcoholics.

We have reported that the serum level of amylase, different from other pancreatic enzymes, increases temporarily after abstinence in alcoholics. To elucidate the mechanism of this phenomenon, pancreatic isoamylase, salivary isoamylase, and amylase in urine were measured together with total serum amylase. Total serum amylase, pancreatic isoamylase, and salivary isoamylase values were measured in 38 male patients admitted to the National Alcoholism Center, Kurihama Hospital, for alcoholism after abstinence. In an investigation of amylase secretion, amylase in urine was measured in some patients after abstinence. In the group with abnormally high total serum amylase on admission, levels were found to decrease after abstinence. In patients with pancreatic disorders in this group, abstinence leads to a decrease in total serum amylase, but in patients with no such disorders, total serum amylase increases temporarily due to increases in salivary isoamylase. In the group with normal total serum amylase on admission, levels increased sharply after abstinence, and both pancreatic isoamylase and salivary isoamylase contributed to the gains. In the group with low total serum amylase, a sharp increase of 2-fold or more was noted after abstinence, and a major contributor was pancreatic isoamylase. The ratio of urine amylase to total serum amylase gradually declined, indicating clearly that abstinence led to a decrease in the excretion of amylase in urine. In cases of heavy alcohol consumption, a decrease in the production or secretion of pancreatic isoamylase and salivary isoamylase while drinking could happen. It was thus suggested that the increase in serum amylase might be due to the fact that this situation is improved by abstinence, plus the fact that excretion of amylase in urine increases during alcohol consumption, and abstinence brings about a decline in such excretion. Measurement of total serum amylase is not appropriate for diagnosing pancreatitis in alcoholic patients or those who consume large quantities of alcohol.

Antagonism of Trichoderma species on Cladosporium herbarum and their enzimatic characterization

The verrucose caused by Cladosporium herbarum reduces production and quality of Passion fruit (Passiflora edulis Sims.), a largely consumed tropical fruit. This work aimed to investigate the antagonism of Trichoderma species (T. polysporum, T. koningii, T. viride and T. harzianum) against Cladosporium herbarum, and to study the production of extracellular hydrolytic enzymes by the pathogen and the antagonists. The results showed considerable antagonistic potential for the biocontrol of C. herbarum isolates by all Trichoderma species, except T. koningii. The most distinguished effect was observed for T. polysporum. In relation to the pattern of esterase obtained by electrophoresis in poliacrylamyde gel, the major activity presented by the isolates was observed after five days of incubation. The C. herbarum isolates produced extracellular enzymes, lipase, pectinase, cellulase, and protease, all possibly related to the infection process. Amylase excretion, not known to be associated with phytopathogens, was detected in Trichoderma species, but not in C. herbarum. In addition to amylase, all Trichoderma species tested produced also extracellular cellulase and pectinase, except T. koningii in relation to the latter enzyme. The demonstration of various esterase isoenzymes in zymograms of the Trichoderma species and C. herbarum isolates was markedly improved by washing the mycelia with detergents or EDTA. This fact suggested that a major fraction of extracelular enzymes may remain attached to outside fungal cell wall after being excreted.

Ethanol administration delays recovery from acute pancreatitis induced by exocrine hyperstimulation

Alcohol consumption causes acute alcohol pancreatitis and worsens the prognosis; however, there is no useful model for elucidation of the mechanism underlying this worsening. The aim of our study was to establish a new prognostic model of acute alcohol pancreatitis in rats. To ascertain the effect of continuous infusion of ethanol on each phase, i.e., progression and recovery, in caerulein-induced pancreatic injury in rats, we infused a physiological or supramaximal dose of caerulein intravenously to conscious Wistar rats for up to 6 h (time: 0–6 h) with or without ethanol infusion for 9 h (time: 3–12 h). Ethanol did not induce the pancreatic injury alone or when combined with a physiological dose of caerulein. In the progression phase, ethanol infusion for 3 h (time: 6 h) did not aggravate the pancreatic injury induced by a supramaximal dose of caerulein in terms of plasma amylase and lipase activities but did increase the pancreatic calcium level. In the recovery phase, however, ethanol infusion for 9 h (time: 12 h) significantly restrained the recovery from pancreatic injury as monitored in terms of these activities. Further, ethanol infusion for 9 h significantly increased the cumulative urinary excretion of amylase from 12 to 27 h but did not do the same from 0 to 12 h. In the histological evaluation at 27 h, the induction of acinar cell vacuolization and dilation of the glandular lumina and ducts were significant in the caerulein plus ethanol-treated group. Our findings suggest that ethanol administration delays the recovery rather than worsens the progression in acute pancreatic injury induced by exocrine hyperstimulation, and we consider our experimental model to be a useful tool for studying the pathogenesis of worsening prognosis in acute alcohol pancreatitis.

Hyperamylasemia after cardiopulmonary bypass: Pancreatic cellular injury or impaired renal excretion of amylase?

Background: Postoperative hyperamylasemia and even acute pancreatitis are associated with coronary artery bypass grafting (CABG). The mechanism of hyperamylasemia and pancreatic acinar cell damage was studied in 20 patients undergoing CABG. Methods: Serial blood and urine samples at eight time points before, during, and 24 hours after the CABG were collected. Salivary and pancreatic isoamylases, the fractional clearance of isoamylases (i.e., relative to creatinine clearance), pancreatic phospholipase A2 (a specific serum marker of pancreatic acinar cell injury), and cystatin C (a sensitive marker of glomerular filtration rate) were measured. Results: Mild serum hyperamylasemia (300 to 1000 units/L) was found in 11 of 20 (55%) and severe (>1000 units/L) in 6 of 20 (30%) patients with no signs of clinical acute pancreatitis. Hyperamylasemia occurred from 6 to 24 hours after the CABG and was mainly caused by pancreatic isoamylase. Serum pancreatic phospholipase A2 concentration remained unchanged, which excludes acinar cell damage. Although renal glomerular filtration was normal during CABG as measured by serum cystatin C and creatinine clearance, the fractional clearance of isoamylases decreased. Conclusions: The decreased rate of excretion into urine, rather than pancreatic cellular damage, is the major source of hyperamylasemia after CABG. (Surgery 1998;123:504-10.)

Characterization and distribution of amylases during vegetative cell growth and sporulation ofClostridium perfringens

Clostridium perfringens produced eight extracellular and two intracellular amylolytic activities when examined by zymograms following polyacrylamide gel electrophoresis under native conditions. The major intracellular amylase was isolated from vegetative cells of C. perfringens. It possessed an estimated molecular mass of 112 kDa. Sulfhydryl and phenol functional groups were essential to its activity. The amylase was endo-acting on starch and also hydrolyzed pullulan. Polyclonal antisera against a purified extracellular amylase did not cross-react with intracellular amylase and the two amylases were biochemically different. The distribution of extracellular amylolytic activities of sporulating cells was different from that of vegetative cells, whereas the distribution of intracellular amylolytic activities remained identical. A significant increase of a particular amylase (A8) occurred in the extracellular fluid during sporulation compared with that during vegetative growth. Regulation of the excretion of amylase(s) may be sporulation and enterotoxingenicity related.

Clinical determinants of glucose homeostasis after pancreas transplantation.

Although successful simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia in the majority of diabetic recipients with end-stage renal disease, little is known about the factors that influence long-term endocrine function. In this prospective study of 48 bladder-drained SPK patients, 209 oral glucose tolerance tests were performed between 3 months and 6 years after transplantation. Normal fasting glucose levels and systemic hyperinsulinemia were stable for up to 6 years after SPK. Multivariate analysis revealed that increased area-under-curve (AUC) levels of C-peptide 3 months after transplantation were predicted by short surgical pancreas anastomosis time, greater recipient body weight, and total HLA mismatch score. Episodes of acute pancreas rejection were not associated with reduced allograft insulin output in the long term. Insulin output, stimulated by oral glucose tolerance tests and assessed by the ratio of AUC insulin to AUC glucose, fell gradually after transplantation and was decreased by an elevated serum calcium level and high cyclosporine dose. The ratio of fasting insulin to glucose, which acts as a marker of peripheral insulin resistance, fell with time after transplantation and was increased by greater body weight, higher prednisolone dose, and lower cyclosporine dose. The inhibitory effect of cyclosporine on both fasting and postprandial insulin output was, however, minor when quantified by multivariate analysis. Endocrine function of the transplanted pancreas was not correlated with its exocrine function measured by urinary amylase excretion, nor was there a correlation with change in renal function measured by isotopic glomerular filtration rate. In summary, simultaneous pancreas and kidney transplantation leads to excellent long-term glucose homeostasis maintained at the expense of systemic hyperinsulinemia. The key factors adversely affecting peripheral resistance in SPK were corticosteroid therapy, body weight, and time after transplantation. The susceptibility of islets to ischemia-reperfusion injury, as quantitated by surgical anastomosis time, may have implications for islet transplantation programs, as may the relative resistance of islets to allograft rejection. Glucose homeostasis after SPK, while remaining abnormal, may be used as the standard against which islet transplantation must be measured.

Effect of glucose on sporulation and extracellular amylase production byClostridium perfringens type A in a defined medium

The effect of glucose and other sugars on sporulation and extracellular amylase production byClostridium perfringens NCTC 8679 type A in a defined medium was studied. Cells grown in the presence of glucose and mannose yielded the highest levels of amylase activity, while disaccharides such as lactose, maltose, and sucrose resulted in moderate amylase production. Little amylase activity was detected in the medium in the presence of ribose or galactose. The concentration of each sugar resulting in highest amylase production was between 6 and 10mm except for fructose (25mm). Levels of heat-resistant spores decreased as sugar concentrations increased. The addition of even small amounts of glucose to the medium before exponential growth suppressed sporulation but maximized amylase activity. The addition of glucose after the initiation of sporulation did not inhibit spore formation. However, its addition to 3-h amylase-producing cells did inhibit subsequent sporulation but promoted the continued excretion of amylase. The different response to glucose between sporulating cells and amylase-producing cells suggests that the mechanisms of catabolite repression of extracellular amylase production and sporulation are distinct in this strain ofC. perfringens.

A laboratory model for evaluation of posttransplant pancreatic exocrine secretion.

Monitoring of urinary enzymuria has been utilized to detect allograft dysfunction after pancreas transplantation with pancreaticocystostomy. In addition, pharmacologic exocrine suppression has been advocated to minimize bicarbonate and protein wasting. Ensuring the validity of these approaches requires controlling both for immunologic alterations in transplant function and for the renal excretion of amylase, bicarbonate, and protein. Toward this end, adult mongrel dogs were divided into two groups. Group A animals underwent distal pancreatectomy alone, and group B animals underwent distal pancreatectomy with autotransplantation and pancreaticocystostomy. In each group, amylase, bicarbonate, and protein output were determined over a 5-hour period in the basal state, during a continuous infusion of octapeptide-cholecystokinin (OP-CCK) at 125 ng/kg/hour, and during a continuous infusion of OP-CCK (125 ng/kg/hour) plus a bolus injection of one clinical unit of secretion per kilogram. Bicarbonate output was not significantly different in the groups with and without autografts. Compared to nonautograft experiments, a statistically significant increase in amylase output was demonstrated in the autograft animals. An increase in protein output was also demonstrated in the autograft experiments, and this increase was statistically significant in the OP-CCK group and the OP-CCK and secretin group. In addition, compared to basal autograft secretion, OP-CCK and OP-CCK plus secretin stimulation resulted in a sustained and significant increase in urinary amylase and protein secretion, indicating preserved sensitivity of the denervated pancreas to exogenous hormones. These results indicate that the canine segmental pancreatic autograft model with pancreaticocystostomy is a suitable model to identify agents associated with exocrine inhibition after transplantation.

Methyl Group Metabolism in the Pancreas of Folate-Deficient Rats

Several studies have suggested that the metabolism of one-carbon compounds may have a special role in the function of the exocrine pancreas. An amino acid-defined diet was used to produce folate deficiency in a group of male rats. These rats were compared with a group of rats pair-fed the same diet supplemented with adequate folate and with a third group fed the folate-supplemented diet with ad libitum access. Pancreatic folate concentrations were already severely depleted after 4 wk of feeding the deficient diet (0.95 +/- 0.10, 5.81 +/- 0.29 and 4.58 +/- 0.30 nmol/g for the deficient, pair-fed control and ad libitum-fed control groups, respectively). The level of folate present in the pancreas of nondeficient animals was second only to that reported for liver. Urinary amylase excretion by animals in the deficient group was higher than that by the other groups (245.5 +/- 21.9, compared with 181.9 +/- 14.5 and 195.3 +/- 10.9 units/mg creatinine for the deficient, pair-fed control and ad libitum-fed control groups, respectively) after 4 wk. The ratio of S-adenosylmethionine to S-adenosylhomocysteine was 18.6 +/- 1.6 and 14.5 +/- 1.0 after 4 wk for the ad libitum-fed control and pair-fed control groups, respectively, but was significantly lower at 6.3 +/- 1.1 for the deficient group. These results indicate a profound effect of folate deficiency upon methyl group metabolism of the pancreas and suggest that this may result in decreased pancreatic function.