Effect of aspirin and indomethacin on epidermal growth factor secretion in duodenal tissue fragments cultivated in vitro.

The aim of the present study was to determine the effect of aspirin and indomethacin on epidermal growth factor (EGF) secretion in duodenal tissue fragments cultivated in vitro. The fragments were obtained from healthy subjects by gastroscopy, cultured in McCoy's medium and gassed with 95% O2 and 5% CO2 at 37 degrees C. After an incubation of 30 min, the culture medium was decanted, and the quantity of hormone determined by radioimmunoassay. The mean EGF level detected in the medium was 10.94 ng/mg protein tissue. The addition of aspirin (final concentration 10(-7) M) to the medium reduced mean EGF levels to 7.5 ng/mg (p less than 0.05), whereas aspirin 10(-8) M did not produce such a modification. The addition of indomethacin (final concentration 10(-8) M) decreased mean EGF levels to 5.37 ng/mg (p less than 0.001). In all experimental conditions, the addition of anti-somatostatin (SRIF) antibodies determined a remarkable increase in EGF (p less than 0.01). The results of this study show aspirin and indomethacin to be direct, not SRIF-mediated inhibitors of EGF release.

Role of vasoactive intestinal polypeptide (VIP) and endogenous somatostatin on the secretion of epidermal growth factor (EGF): studies on duodenal tissue cultures.

Epidermal Growth Factor (EGF)-containing cells have been found in Brunner's glands in the same area where several regulatory peptides are released. The present study was aimed at testing the release and the regulation of EGF secretion from cultured duodenal biopsies obtained from healthy individuals by gastroscopy. The effects and the interaction of VIP and somatostatin on the hormone release were studied. Duodenal biopsies were cultured at 37 degrees C in Mc Coy's buffer, gassed with 95% O2 and 5% CO2. After 30 min, the culture medium was decanted for the measurement of the hormones by RIA. To measure the protein content, the tissue was then homogenized; EGF detected in the culture was 11.5 ng/mg protein. The addition of VIP in the medium increased EGF mean levels to 21.6 ng/mg protein (P less than 0.01). The biopsies thus obtained were cultured with anti-somatostatin antibodies to evaluate the influence of endogenous somatostatin on EGF secretion. The inclusion of anti-somatostatin antibodies increased the EGF levels to 41.2 ng/mg protein (P less than 0.01). The combined addition of anti-somatostatin antibodies and VIP in the culture caused a mean EGF increase significantly higher than the values obtained separately by VIP and somatostatin (P less than 0.01). In conclusion, we can suggest a triangular interaction model of EGF release, where the somatostatin seems to be the negative monitor of over-secreted VIP and EGF from the gut.

Interactions between endogenous and exogenous insulin and human pancreatic polypeptide secretion.

The relationships between exogenous and endogenous insulin and plasma human pancreatic polypeptide (hPP) were investigated. Three tests were performed in 8 healthy subjects: 1 degree--1 g tolbutamide was injected i.v. in 1 min., 2 degrees--50 ml 50% glucose solution and 7 U of Insulin were contemporaneously infused at constant rate for 60 min., 3 degrees--50 ml saline solution were infused as control. After the tolbutamide injection plasma glucose levels were unchanged between 0-10 min. At 5, 10, 15 min. an increase in C-Peptide (CPR) value and a significant decrease of hPP were observed. At 15, 30 and 45 min. plasma glucose was significantly lower than baseline and hPP levels strongly rose until the end of the test. The glucose-insulin infusion testing resulted in a rise in plasma glucose and CPR levels at 15 min. and a fall in plasma hPP at 30 min. The present findings suggest that in the first part of tolbutamide test, the endogenous insulin secretion, valued as CPR, seems to inhibit hPP release probably through a paracrine pathway.

Effects of heroin addiction on the responses of glucose, C-peptide and insulin to a standard meal.

1. The aim of the study was to examine the responses of plasma glucose, C-peptide immunoreactivity (CPR) and total immunoreactive insulin (IRI) to a standard meal in heroin addicts, since the presence of immunoreactive beta-endorphin has been demonstrated in human endocrine pancreas. 2. Ten heroin addicts and 10 control subjects participated in the study. The addicts had been taking heroin (from 0.5 to 2 g/day) for at least 2 months and they had no detectable diseases. 3. After a 12 h fast, each subject received a standard meal; blood samples were taken at -15, 0, 15, 30, 60 and 120 min to determine glucose, CPR and IRI. Calculation of the CPR/IRI molar ratio was used as a semiquantitative estimation of the hepatic extraction of insulin. 4. No difference in plasma glucose was observed between the groups. Addicts had lower CPR than normals at 15, 30 and 120 min (P less than 0.01). On the contrary, IRI was higher in addicts than in normals (P less than 0.05 at -15 and 0 min, P less than 0.01 at 15, 30 and 60 min), except at 120 min. The CPR/IRI molar ratio was lower in addicts (P less than 0.01). 5. Heroin addiction seems to produce a beta-cell failure and contemporaneously a state of hyperinsulinaemia; blood glucose remains in the normal range. 6. We conclude that chronic heroin addiction may produce a change in the rate of hepatic extraction of insulin.