Serum Trypsin Concentration Research Articles

Pancreatic biomarkers: role in diabetes mellitus

Diabetes mellitus refers to a group of diseases that cause high blood sugar levels. The most common type is type 2 diabetes, which is caused by insulin resistance and inadequate insulin production. However, diabetes can also result from conditions affecting the exocrine pancreas. Both type 1 and type 2 diabetes patients may experience changes in their pancreatic exocrine function, leading to reduced levels of fecal elastase-1 in many cases. This review article focuses on the role of specific pancreatic biomarkers in diabetes mellitus, including cholecystokinin, trypsin, chymotrypsin, carboxypeptidase, amylase, lipase, secretin, elastase-1, and retinol-binding protein 4 about recent advances and discoveries, significant gaps in the literature, current debates, and potential directions for future research related to these biomarkers about diabetes mellitus. This review article discusses various biomarkers related to pancreatic exocrine and endocrine function and their implications in diabetes. It suggests that gut cholecystokinin may play a role in lowering glucose synthesis through a neural network and resistance to it could contribute to hyperglycemia in diabetic patients. It also discusses the use of various markers such as serum trypsin concentration, amylase and lipase levels, pancreatic elastase levels, and fasting secretin levels to assess pancreatic exocrine function. Additionally, the article explores the role of carboxypeptidase E in the endocrine and neurological systems and its association with disorders. Moreover, it also highlights the involvement of retinol-binding protein 4 in the development of type 2 diabetes and insulin resistance.

On the Activities of Pancreatic Proteases and Alpha-1 Proteinase Inhibitor in Meat-Type Chicken

The study was aimed at the evaluation of the effects of breed, age, different digestion stimulators, and dietary crude protein (CP) level on the activities of proteolytic enzymes in pancreatic tissue and duodenal chymus (in vivo), serum trypsin and α1-proteinase inhibitor (A1PI) concentrations in meat-type chicks. The study of age dynamics of trypsin and A1PI concentrations was performed on the chicks of hybrid cross “Smena-8”and two parental lines (Plymouth Rock and Cornish) fed standard commercial corn-wheat-SBM diets. Twenty birds per breed were euthanized at 1, 7, 14, 21, 28 and 35 days of age to obtain blood samples and pancreatic homogenate. Experiments on the effects of different digestion promotors (probiotic, acidifier, phytobiotic, enzymatic preparation) and different CP levels (finisher diet, CP 20%, vs. ground corn, CP 8.5%) were performed on 12 hybrid chicks with fistulated duodenum from 14 to 50 days of age. The following conclusions were made: 1) At 1 day of age high proteolytic activity in pancreatic tissue and maximal serum concentrations of trypsin and A1PI were found in both hybrid and parental lines. Since 7 to 35 days of age A1PI concentration was nearly constant, serum trypsin concentration decreased while proteolytic activity in pancreatic tissue exhibited undulate increase; 2) Proteolytic activity in pancreatic tissue was higher in hybrids compared to the parental lines from 7 to 35 days of age (p 0.05); 3) Supplementation of diet with exogenous enzymes stimulated the digestion due to the increase in protease activity in duodenal chymus by 9.1% compared to unsupplemented control (p 0.05); 4) Proteolytic activity in duodenal chymus significantly responded to the substitution of ground corn for the complete diet by 2-fold decrease while serum trypsin concentration responded by 2.5-fold increase (p 0.001). This fact can indicate that physiological functions of digestive proteases are not confined to the digestive processes.

Endoscopic Ultrasound (EUS), Chronic Pancreatitis, and Pancreatic Cancer (PC) Precursors in High Risk Individuals

EUS and ERCP in high risk individuals (HRI) with an inherited predisposition for PC have shown chronic pancreatitis (CP)-like abnormalities but the significance of these changes has not been understood. AIM: To determine the prevalence of pancreatic EUS abnormalities in asymptomatic HRI and correlate these with ERCP, pancreatic function, and pathology. Methods: In 2 prospective cohort studies (1998–2004), 112 HRI (105 HRI with ≥2 affected first degree relatives with PC, 7 had Peutz-Jeghers syndrome) had screening EUS. ERCP was performed by another endoscopist without knowledge of EUS findings. Serum trypsin and secretin stimulated-peak bicarbonate concentration was measured in HRI and normal controls. Surgery was performed for suspected neoplasms or dysplastic tissue in EUS-FNA. Pancreata were examined by an experienced pathologist. Results: The prevalence of EUS changes of CP (≥4 of 9 features) in HRI was 72.3%. Mild ERCP abnormalities were present in 85.6%. Serum trypsin was lower in HRI than in controls (mean=66.4 vs. 169.1, p=.0001). But, mean peak bicarbonate concentration was similar in HRI and controls (106.8 meq/L vs. 105.4 meq/L, respectively, p=0.83). Subtotal pancreatectomy was performed on 15 HRI: pancreatic neoplasms were found in 11 and pancreatic intraepithelial neoplasia (PanIN) 1–3 were present in 13. The mean PanIN density in HRI pancreata was 12.2% (range 1–27.3%). Both IPMNs and PanIN were associated with parenchymal lobulocentric atrophy and CP. PanIN density was positively and linearly correlated with the number of EUS features of CP (Spearman's R=0.87, p=.005) but not ERCP grade of CP (Spearman's R=0.41, p=.31). Conclusions: EUS features of CP are highly prevalent in HRI with an inherited predisposition to PC and are associated with both IPMN and PanI. EUS features of CP correlate with PanIN density and PanIN-associated lobulocentric atrophy.

Clinical usefulness of a trypsin radioimmunoassay kit

From the clinical use of RIA-gnost trypsin kit, the following results were obtained. 1. Standard curve showed a steep and good curve was shown. 2. Incubation: The condition for the first incubation was set at the room temperature for 10-24 hours and that for the second incubation at the room temperature for 3-5 hours. With these settings, satisfactory results were obtained. 3. Reproducibility and recovery: The C.V. of the reproducibility and the recovery were considered superior, and the values were below 10% and +/- 3%, respectively. 4. Correlation between trypsin and serum elestase-1: An excellent positive correlation (coefficient of correlation r = 0.889) was shown. 5. Serum trypsin concentration of normal and pancreatic diseases: The normal range was from 100 to 500 ng/ml. Acute pancreatitis rose obviously. Diabetes mellitus and chronic pancreatitis was below 500 ng/ml and the pancreatic cancer showed a tendency to scatter in the range of 50-1,250 ng/ml. The above results indicated that serum trypsin can be easily measured with high precision by using this method. Thus the method is considered useful for the diagnosis of pancreatic diseases.

Generalized Amyloidosis

A new case of cystic fibrosis complicated with secondary amyloidosis is reported. We reviewed ten cases described up to now in the literature, emphasizing the rarity of this association. The usefulness of serum trypsin concentration as an index of exocrine pancreatic function and the accuracy and simplicity of the abdominal fat biopsy in the histologic diagnosis of amyloidosis were evaluated.

Influence of inactivation of trypsin on immunoreactivity and serum immunoreactive trypsin concentration measured by radioimmunoassay.

The influences of various active site-specific reagents of trypsin and protease inhibitors on the immunoreactivity of trypsin and serum trypsin concentration have been studied by radioimmunoassay (RIA). The RIA using inactivated 125I-trypsin as tracer showed lower Bo/T than the RIA using active 125I-trypsin, but the coefficient of variance of the former was smaller than that of the latter. Normal serum trypsin concentrations were 26.12-36.38 ng/ml with the RIA using inactivated 125I-trypsin as antigen tracer, and 201.15 ng/ml with the RIA using active 125I-trypsin as tracer. The recovery experiment showed that the difference was due to the interaction of serum protease inhibitors and labeled active trypsin.

Serum phospholipase A2, immunoreactive trypsin, and trypsin inhibitors during human acute pancreatitis.

Serum immunoreactive trypsin and phospholipase A2 were analyzed at regular intervals in seven patients hospitalized as a result of acute hemorrhage pancreatitis. alpha 1-Antitrypsin and alpha 2-macroglobulin levels and trypsin-inhibitor capacity of serum were determined simultaneously. Serum trypsin concentrations were markedly raised in all patients. The levels of immunoreactive trypsin remained elevated for longer periods than those of urinary amylase. alpha 1-Antitrypsin and trypsin-inhibitor capacity were also significantly increased as compared with the post-illness values, but alpha 2-macroglobulin decreased considerably, reaching the lowest levels on the 5th day after admission. Consequently, phospholipase and trypsin are released to the circulation during hemorrhagic pancreatitis, but the increase in trypsin is compensated for by an increase in trypsin-inhibitor capacity of serum due to elevated alpha 1-antitrypsin levels. The decrease of alpha 2-macroglobulin in hemorrhagic pancreatitis was one of the most interesting findings, and it is proposed that this inhibitor may be consumed in the elimination of proteases through the reticuloendothelial system. The two patients who died had higher phospholipase values than those who recovered, but the prognosis could not be predicted from the values of the other measured variables.

Origin of circulating serum immunoreactive trypsin in man.

Serum trypsin concentrations within the portal venous system have been measured in man during transhepatic portal venography in an attempt to determine its source. In eight experiments, mean serum trypsin concentration at the splenic hilum was 180 +/- 25 ng/ml (mean +/- SEM). Trypsin concentration in the rest of the splenic vein was not significantly different. The mean concentrations in the portal vein (210 +/- 32 ng/ml) and within the superior mesenteric vein (233 +/-- 29 ng/ml) were, however, significantly higher than at the hilum (P less than 0.05). Following cholecystokinin-pancreozymin (CCK-PZ) and secretin stimulation, marked increases in serum trypsin concentration were seen within the portal vein (two patients) and deep within the superior mesenteric (two out of three patients). We conclude that circulating serum trypsin is derived, at least in part, from intestinal reabsorption.

Clinical value of serum immunoreactive trypsin concentration

The clinical value of estimation of serum concentrations of immunoreactive trypsin was evaluated by studying 46 healthy controls, 23 controls in hospital, 44 patients with chronic pancreatic disease, and 184 patients with non-pancreatic conditions in which pancreatic disease commonly enters into the differential diagnosis. Serum trypsin concentration had a log normal distribution in the controls, and the calculated normal range was considerably wider than that previously reported. The concentration was abnormal in only 13 out of 27 patients with chronic pancreatitis and was extremely variable in patients with pancreatic cancer. Abnormal results occurred in 11% of the patients with non-pancreatic disease. Eighteen patients had a subnormal trypsin concentration, of whom six did not have pancreatic disease and 12 had either chronic pancreatitis or pancreatic cancer. There was no correlation between serum trypsin concentration and mean tryptic activity as measured by the Lundh test. Of 11 patients with pancreatic steatorrhoea, only seven had subnormal trypsin concentrations. There results suggest that the serum concentrations of immunoreactive trypsin has a low specificity and sensitivity for pancreatic disease and does no reflect the degree exocrine insufficiency in patients with proved chronic pancreatitis.

Clinical value of serum immunoreactive trypsin concentration.

The clinical value of estimation of serum concentrations of immunoreactive trypsin was evaluated by studying 46 healthy controls, 23 controls in hospital, 44 patients with chronic pancreatic disease, and 184 patients with non-pancreatic conditions in which pancreatic disease commonly enters into the differential diagnosis. Serum trypsin concentration had a log normal distribution in the controls, and the calculated normal range was considerably wider than that previously reported. The concentration was abnormal in only 13 out of 27 patients with chronic pancreatitis and was extremely variable in patients with pancreatic cancer. Abnormal results occurred in 11% of the patients with non-pancreatic disease. Eighteen patients had a subnormal trypsin concentration, of whom six did not have pancreatic disease and 12 had either chronic pancreatitis or pancreatic cancer. There was no correlation between serum trypsin concentration and mean tryptic activity as measured by the Lundh test. Of 11 patients with pancreatic steatorrhoea, only seven had subnormal trypsin concentrations. There results suggest that the serum concentrations of immunoreactive trypsin has a low specificity and sensitivity for pancreatic disease and does no reflect the degree exocrine insufficiency in patients with proved chronic pancreatitis.

Serum trypsin concentration and pancreatic trypsin secretion in insulin-dependent diabetes mellitus

Fasting serum trypsin concentration and pancreatic trypsin output, stimulated by secretin and cholecystokinin-pancreozymin, were measured in 18 patients with insulin-dependent diabetes, to assess a possible correlation between these two indices of exocrine pancreatic function. Serum trypsin concentration was subnormal in 13, and pancreatic trypsin output was decreased in 14 patients, but there was no significant correlation between the two measurements. There was no correlation between serum trypsin and residual beta cell function measured by plasma C-peptide immunoreactivity (CPR). After an interval of four years serum trypsin measurements were repeated in 11 subjects. All individual trypsin levels were lower than the previous results, the difference being highly significant ( t = 9.0; p < 0.001). Serum trypsin concentration therefore represents a qualitative index of reduced exocrine pancreatic function in diabetes, but has no value in quantitating the degree of deficiency.

Immunoreactive serum trypsin in diseases of the pancreas.

Immunoreactive serum trypsin was measured with a double antibody radioimmunoassay in normal subjects and patients with various diseases of the pancreas. The normal range is 115-350 ng/ml with a geometric mean of 212 ng/ml. No trypsin was found in serum after total duodenopancreatectomy, in about 75% of patients with cystic fibrosis and in a few patients with pancreas carcinoma or chronic pancreatitis. Reduced serum trypsin levels between 10 and 100 ng/ml were measured in the remaining 25% of cystic fibrosis and in one third of the patients with chronic pancreatitis. Serum trypsin was increased to 700-17,000 ng/ml in all patients with acute pancreatitis or during the acute phase of chronic pancreatitis. Absent or reduced serum trypsin is a reliable indicator of total or partial exocrine pancreatic insufficiency whereas considerably increased serum trypsin concentration do indicate acute pancreatitis.

Serum immunoreactive trypsin concentration after a Lundh meal. Its value in the diagnosis of pancreatic disease.

The changes in serum trypsin concentration have been measured in 47 subjects for up to 2 hours after a Lundh meal. In 18 healthy controls, mean fasting trypsin concentration was 285 +/- 125 ng/ml (mean +/- 2 SD). The maximum increase after the Lundh meal (the trypsin response ratio) was 6.7 +/- 7.5%. Six patients with chronic renal failure had elevated fasting serum trypsin concentrations (range 460-1100 ng/ml) but trypsin response ratios fell within the control range. Of five patients with relapsing pancreatitis, two had raised and three normal or low fasting trypsins. After stimulation two had elevated trypsin response ratios; one of the two had evidence of main duct obstruction. Eleven out of 12 patients with chronic pancreatitis (with or without insufficiency) had low fasting trypsin concentrations (range 0-120 ng/ml) Seven of the 12 also had raised trypsin response ratios. In six patients with cancer of the pancreas, fasting trypsin was low in three, normal in two, and raised in one. Both patients with a normal fasting level had a raised trypsin response ratio. The combination of a single estimation of fasting serum trypsin concentration followed by serial measurements after a Lundh meal provides a useful screening test for chronic pancreatic disease.

An Evaluation of Serum "Trypsin" Tests

Abstract When crystalline trypsin was dissolved at various concentrations in pooled serum, the rates of hydrolysis of α-benzoyl-1-arginineamide (BAA) and N-α-benzoyl-dl-arginine-β-naphthylamide (BANA) were not linear functions of the trypsin concentration. Also, the plot of trypsin activity in relation to trypsin concentration differed with different sera. The apparent tryptic activity toward these substrates is felt to be a function of the concentration of serum trypsin inhibitor and, with BANA only, some unidentifed proenzyme which is activated by trypsin. Therefore, it is concluded that it is not feasible to measure serum trypsin concentration with these substrates.