Pancreatic Secretory Activity Research Articles

EXOCRINE PANCREATIC FUNCTION IN CHICKENS AS A RESULT OF ADDING FEED ACIDIFIERS IN THEIR DIET

Feed acidifiers are used in animal diets for the prevention of proliferation of intestinal pathogenic microorganisms and resulting gastrointestinal digestive disorders. These additives, containing organic acids, have also been found to improve productivity and feed efficiency in poultry. There is information about correlation between digestive enzymes’ activity and intestinal microbiota of meattype chickens. However, the exact mechanism of the beneficial impact of organic acids on the digestion system still remains understudied. The paper presents the results of experiments conducted on Hisex White chicken with chronic fistulae of the main pancreatic duct, fed on a diet supplemented with an acidifier containing 2-furoic acid. No significant effect of this acidifier was found on the digestive pancreatic function. The dynamics analysis showed that the chickens’ secretion rate of pancreatic juice after postprandial 30 minutes dropped by over two times in the testing period when using acidifiers in their diet. After 150 minutes this rate was lower by 27.3% compared to the control group, which corresponds the neurochemical phase of secretory regulation. Analysis of enzyme dynamics (amylase, lipase and protease) showed a slight increase in the activity of proteases in pancreatic juice (by 1.2- 12.4%), compared to the control group, in the phase of complex-reflex regulation of pancreatic secretory activity related to the recognition of the taste qualities of the feed. Feed conversion ratio in the test group of broiler chickens increased by 1.52% when using acidifiers in the diet. The result of the study showed that the use of acidifiers has a beneficial effect on chickens’ gastrointestinal digestion as well as an inhibitive action on intestinal pathogens.

Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats.

Aerobic exercise training can improve insulin sensitivity in many tissues; however, the relationship among exercise, insulin, and cancer cell growth is unclear. We tested the hypothesis that aerobic exercise training begun during adolescence can attenuate Walker 256 tumor growth in adult rats and alter insulin secretion. Thirty-day-old male Wistar rats engaged in treadmill running for 8 weeks, 3 days/week, 44 min/day, at 55–65% VO2max until they were 90 days old (TC, Trained Control). An equivalently aged group was kept inactive during the same period (SC, Sedentary Control). Then, half the animals of the SC and TC groups were reserved as the control condition and the other half were inoculated with Walker 256 cancer cells, yielding two additional groups (Sedentary Walker and Trained Walker). Zero mortalities were observed in tumor-bearing rats. Body weight (BW), food intake, plasma glucose, insulin levels, and peripheral insulin sensitivity were analyzed before and after tumor cell inoculation. We also evaluated tumor growth, metastasis and cachexia. Isolated pancreatic islets secretory activity was analyzed. In addition, we evaluated mechanic sensibility. Our results showed improved physical performance according to the final workload and VO2max and reduced BW in trained rats at the end of the running protocol. Chronic adaptation to the aerobic exercise training decreased tumor weight, cachexia and metastasis and were associated with low glucose and insulin levels and high insulin sensitivity before and after tumor cell inoculation. Aerobic exercise started at young age also reduced pancreatic islet insulin content and insulin secretion in response to a glucose stimulus, without impairing islet morphology in trained rats. Walker 256 tumor-bearing sedentary rats also presented reduced pancreatic islet insulin content, without changing insulin secretion through isolated pancreatic islets. The mechanical sensitivity test indicated that aerobic exercise training did not cause injury or trigger inflammatory processes prior to tumor cell inoculation. Taken together, the current study suggests that aerobic exercise training applied during adolescence may mitigate tumor growth and related disorders in Walker 256 tumor-bearing adult rats. Improved insulin sensibility, lower glucose and insulin levels and/or reduced insulin secretion stimulated by glucose may be implicated in this tumor attenuation.

Nutrition in Cystic Fibrosis

Cystic fibrosis (CF) is mostly recognized for its pulmonary morbidity, but the earliest manifestations of the disease are related to its gastrointestinal and nutritional derangements. Destruction of acinar pancreatic tissue, pancreatic ductular obstruction, and lack of enzymatic activity lead to malabsorption (particularly of fats), diarrhea, and failure to thrive. A minority of CF patients carrying milder CF transmembrane conductance regulator (CFTR) mutations have preserved pancreatic secretory activity and are free from significant malabsorption early in life. However, these patients are at risk for losing pancreatic function over time. Nutritional status plays an important role in the progression of the pulmonary disease in CF. Further, CF patients with better nutritional status have a survival advantage. Several factors contribute to impaired nutritional status in CF (e.g., pancreatic insufficiency, chronic malabsorption, recurrent sinopulmonary infections, chronic inflammation, increased energy expenditure, suboptimal intake). Progressive lung disease further increases calorie requirements by increasing the work of breathing. Treatment programs that place an emphasis on higher caloric intake and more aggressive nutritional management in CF patients report better outcomes. Basic tenets of nutritional repletion in CF include the use of pancreatic enzyme replacement therapy and following a high calorie, high protein, unrestricted diet. At the Stanford Cystic Fibrosis Center, nutritional status is assessed on an ongoing basis through anthropometric parameters and annual assessment of body composition, bone density, glucose tolerance, and various biochemical and micronutrient levels. Based on the anthropometric data obtained on routine clinical encounters, patients are categorized as to their nutritional risk. This proactive approach for the early identification of nutritional risk has become a major theme within the network of US CF centers. Aggressive nutritional support with adequate pancreatic replacement management should lead to both normal growth and lung function preservation. In addition, nutritional status has to be monitored closely during routine encounters to allow for early intervention once derangements are noted. This will include increasing calories in the early stages of lung disease and being vigilant of gastrointestinal symptomatology and complications.

Diet in Patients with Acute Pancreatitis

Objective: to define a role of various maintenance modes, such as enteral tube feeding (ETF) and complete parenteral feeding in different phases of acute pancreatitis (AP). Subjects and materials. The impact of various modes of nutritional support on pancreatic secretory activity and the course of AP was comparatively analyzed in 774 patients (mean age 45.3±4.7 years) with AP. The criteria for evaluation of the activities of the pancreas and its inflammatory process activity were considered to be clinical and laboratory parameters (pain, body temperature, hemogram, amylasemia, the degree of dynamic ileus and abdominal inflammatory infiltrate, and the level of gastrointestinal peptides), and ultrasonographic and computed tomographic data. The additional impact of different types of protein-calorie provision on pancreatic secretory activity was studied in 23 patients with external pancreatic fistulas, by using debetometry. Results. ETF was shown to have a stimulating effect on pancreatic secretion and AP worsening when it was used in the early phases of the disease. The optimum time of complete parenteral feeding (days 5—14 after the onset of the disease) and the criteria for the possible initiation of ETF were determined. Emphasis was laid on the important role of enteral feeding in a package of therapeutic measures in AP in the phase of pyonecrotic lesions. Conclusion. The proposed nutritional support tactics along with mini-invasive surgical treatments could reduce postoperative and overall mortality rates to 4.2 and 3.7%, respectively. Key words: acute pancreatitis, protein-calorie provision, nutritional support, enteral tube feeding, parenteral feeding, intestinal lavage, pancreatic secretion.

Circadian pancreatic enzyme pattern and relationship between secretory and motor activity in fasting humans.

It is unknown whether nonparallel pancreatic enzyme output occurs under basal conditions in humans. We aimed to determine whether the circadian or wake-sleep cycle influences the relationship among pancreatic enzymes or between pancreatic secretory and jejunal motor activity. Using orojejunal multilumen intubation, we measured enzyme outputs and proximal jejunal motility index during consecutive daytime and nighttime periods in each of seven fasting, healthy volunteers. Enzyme outputs were correlated tightly during daytime phases of wakefulness and nighttime phases of sleep (r > 0.72, P < 0.001). During nocturnal phases of wakefulness, output of proteases (r = 0.84, P < 0.001), but not of amylase and trypsin (r = 0.12), remained associated. Nocturnally, particularly during sleep, pancreatic secretory activity was directly correlated with jejunal motility index (r > 0.50, P < 0.001). In conclusion, parallel secretion of pancreatic enzymes dominates throughout the circadian cycle. Nonparallel secretion during nocturnal phases of wakefulness may be due to merely circadian effects or to the coupling of the wake-sleep and the circadian cycle. The association between fluctuations of secretory and motor activity appears to be particularly tight during the night.

Plasma PAF acetylhydrolase in non-insulin dependent diabetes mellitus and obesity: effect of hyperinsulinemia and lovastatin treatment

Insulin resistance is characterized principally by impaired insulin-mediated glucose uptake which provokes a compensatory increase in pancreatic β-cell secretory activity. For a time this may produce well-controlled plasma glucose levels but as the insulin resistance worsens the augmented insulin production becomes inadequate to keep plasma glucose at euglycemia leading to the development of non-insulin dependent diabetes mellitus (NIDDM), accompanied by hyperinsulinemia and hyperglycemia. A number of metabolic defects are associated with NIDDM including obesity, hypercoagulability, cardiovascular disease risk factors such as hypertension and dyslipidemia and these constitute the insulin resistance syndrome. The identity of the biochemical factor that might link all these defects is not yet known. We have hypothsisized that platelet-activating factor (1- O-alkyl-2-acetyl- sn-glycero-3-phosphocholine, PAF) may be such a link. In this study, we measured plasma acetylhydrolase (EC.1.1.48), which degrades PAF to the inactive metabolise lyso-PAF, as a surrogate for PAF activity in three groups of hypercholesterolemic subjects: lean controls ( n=9), non-diabetic obese ( n=6) and NIDDM subjects ( n=6). The ages and body mass indices of the subjects were 46±3.1 and 24.2±2.2 for the lean controls, 52±2.5 and 28.7±0.9 for the NIDDM subjects and 60±2 and 27.6±2.1 for the obese, non-diabetic subjects (mean±S.E.M.). The measurements were made before and after therapy with the cholesterol-lowering drug lovastatin, a 3-hydroxy 3 methylglutaryl (HMG) coenzyme A reductase inhibitor (40 mg/day) for 3 months. Fasting plasma glucose (FPG) levels were 91±11, 96±3 and 146±11 mg/dl, for the lean, obese and NIDDM subjects, respectively, before therapy began. Lovastatin did not affect FPG in any of the three subject groups. Before treatment, the fasting plasma insulin (FPI) levels were 6.1±0.92, 10.83±2.03 and 14.68±3.64 mU/l for the lean, non-diabetic obese and NIDDM subjects, respectively. After lovastatin therapy only the obese group exhibited a significant change in FPI (15.35±2.47 mU/l) ( P<0.05). Total cholesterol levels were similar in all three groups both before and after lovastatin therapy but within each group lovastatin therapy significantly reduced the total cholesterol by 32, 29 and 34% in the lean, obese and NIDDM subject groups respectively ( P<0.0001). Lovastatin therapy reduced LDL-cholesterol levels by 40, 32and 46% in the lean, obese and NIDDM subjects, respectively, but produced no significant effect on HDL or triglyceride levels. Before therapy, the plasma acetylyhydrolase activities were 104±7, 164±7 and 179±7 nmol/ml per min in the lean, obese and NIDDM subjects, respectively. Lovastatin therapy reduced plasma acetylhydrolase levels to 70±7, 87±6 and 86±7 nmol/ml per min in the lean, obese and NIDDM subjects, respectively. Plasma acetylhydrolase activity was predominantly (>80%) associated with LDL cholesterol both before and after lovastatin treatment. Also, plasma acetylhydrolase activity significantly correlated with fasting plasma insulin levels before lovastatin therapy but not after. Taken together, this study clearly implicates PAF metabolism in three defects associated with the insulin resistance syndrome; hypercholesterolemia, obesity and NIDDM. Additionally, we conclude that chronic hyperinsulinemia may play a significant role in the production of plasma acetylhydrolase.

Plasma Peptide YY and Pancreatic Polypeptide in Dogs After Long-Term Adaptation to Dietary Fats of Different Degrees of Saturation: Olive and Sunflower Oil

Mongrel dogs from weaning to 6 months of age were fed on one of two diets that differed only in the type of fat content (virgin olive oil or sunflower seed oil) to compare plasma levels of peptide YY (PYY) and pancreatic polypeptide (PP) in the basal period and in response to food. Under resting conditions, blood concentrations of both peptides, measured by specific radioimmunoassays, were significantly higher in the olive oil group. Food intake was not followed by any marked or significant changes in PYY or PP circulating levels, although some rises were observed. On the other hand, plasma PYY reached significantly greater values throughout the postprandial period in the dogs fed on the diet containing olive oil, whereas no differences were recorded between the groups as far as PP is concerned. Our results demonstrate that long-term intake of diets enriched in monounsaturated fatty acids (olive oil) produces significantly higher basal levels of PYY and PP, as well as significantly higher PYY levels in response to food compared with diets containing sunflower oil. The differences, traceable to the composition of the two types of dietary fat supplied, explain the attenuated pancreatic secretory activity observed by us previously in this animal species. This mechanism may be responsible, at least in part, for the adaptation of pancreatic secretion to the quality of dietary fat.

Chromium and other insulin: Sensitizers may enhance glucagon secretion: Implications for hypoglycemia and weight control

Increased pancreatic beta-cell secretory activity usually is associated with decreased alpha-cell activity; stimulated beta-cells release gamma-aminobutyric acid, which hyperpolarizes alpha-cells, inhibiting glucagon release. Thus, insulin secretion and glucagon secretion are usually inversely coupled. This suggests that chromium and other insulin-sensitizing modalities, by down-regulating beta-cell activity, may increase glucagon secretion. Such an effect might play a role in the documented therapeutic activity of supplemental chromium and biguanides in reactive hypoglycemia, and might also be of benefit to dieters.

The endocrine functions of the gut

The first properly described hormone was secretin, a hormone of the gut. In 1902 Bayliss and Starling demonstrated, in dogs, that intravenous administration of small intestinal extracts increased pancreatic secretory activity. Analytical molecular biological, immunological and immunocyto/histo—chemical techniques have identified a dispersed or diffuse endocrine system within the gut—the gastro—enteropancreatic (GEP) endocrine system. Chemical compositional, mechanical and possibly temperature variations within the gut lumen elicit autocrine, paracrine and endocrine responses from GEP cells. Local secretory, absorptive, neural, muscular and haemodynamic activities are thereby co-rdinated to regulate gut motility. The outcome is the successful digestion and absorption of ingested nutrients and in turn appetite, satiety and renal function are influencedietary changes are monitored and the GEP responds appropriately.

Exocrine pancreatic proteins in serum during pancreatic allograft rejection.

The serum concentrations of immunoreactive pancreatic secretory trypsin inhibitor, cationic elastase, anionic trypsin, cationic trypsin, and total amylase activity, were studied after pancreatic allograft transplantation. Nine patients received whole organ pancreaticoduodenal allografts with exocrine drainage to the bladder. Eight of the patients received simultaneously a renal allograft. The serum concentration of immunoreactive cationic elastase increased gradually during the first postoperative days to a peak on the fifth day after surgery; all other proteins decreased in concentration after the first day. Eighteen episodes of pancreatic and/or kidney rejection, diagnosed by means of kidney biopsy, urinary cytology, kidney function, and urinary amylase levels, were analyzed. The pancreatic proteins displayed different patterns in serum concentration during the days immediately before diagnosis of rejection. The pancreatic secretory trypsin inhibitor showed the most pronounced peak in serum concentration during rejection and even reacted during some episodes without a decline in urinary amylase output. Cationic elastase on the other hand showed no reaction at all. From this homogeneous material it is possible to conclude that changes in serum concentrations during rejection are not the same for all pancreatic exocrine proteins.

Periodic fluctuations in pancreatic secretion and duodenal motility investigated in neonatal calves.

To clarify the relative timing of clinical changes in duodenal motility and pancreatic secretion in newborn calves, we recorded duodenal electrical and mechanical activity and analysed pancreatic secretion and migrating myoelectric complex (MMC). In eight calves integrated recordings were derived from sites near the duodenal bulb and pancreatic accessory duct orifice, and pancreatic juice was sampled after an overnight fast, after a feed, and during reversible cold vagal blockade. Peak secretion coincided with duodenal irregular spiking activity and the nadir with absence of spiking. Feeding elicited electrical and mechanical hyperactivity in the duodenum, dissipated the MMC temporarily, and dramatically increased the juice volume and bicarbonate and protein outputs. Periodic fluctuations in secretion started shortly after a feed, as did recovery of the duodenal myoelectric complexes. Cold vagal blockade reversibly disrupted the synchronous changes in duodenal motility and pancreatic secretory activity, though the close association was not totally obliterated. In milk-fed calves interdigestive pancreatic secretion apparently rises and falls in phase with migrating myoelectric complexes of the proximal duodenum and the vagus is largely, though not exclusively, responsible for co-ordinating these changes.

Exocrine Function of the Heterotopic Transplanted Pancreas Segment

We investigated the effect of denervation after heterotopic segmental pancreas autotransplantation on the exocrine function of the graft. The weight of the pancreas segment was determined, and secretory volume, bicarbonate output, and amylase activity were measured before and after i.v. infusion of secretin and cholecystokinin (CCK)-8. The studies were performed in untreated normal dogs, at 2 months postoperatively in partially pancreatectomized dogs with an innervated segment left in situ, and in totally pancreatectomized recipients of denervated heterotopic autotransplanted segments (approximately 30% of whole pancreas). The weight of the pancreas segment was similar in innervated and denervated dogs. Basal pancreatic secretory volume, bicarbonate output, and amylase activity were largely independent of cholinergic control. The secretory volume and bicarbonate output response to i.v. gut hormones (mainly secretin) were slightly modulated by cholinergic activity, whereas amylase response to gut hormones (mainly CCK-8) was quite independent of cholinergic control. We conclude that, after pancreas transplants, the effect of denervation on graft exocrine function is negligible--a finding that is reassuring if preserving of the exocrine tissue is important for optimal endocrine function of the graft.

Reduction and recovery of plasma 1,5-anhydro-D-glucitol level in diabetes mellitus.

The plasma concentration of 1,5-anhydro-D-glucitol (AG) was measured in 135 newly diagnosed patients who were referred for oral glucose tolerance tests. AG concentrations in the nondiabetic patients indicated that the mean value of normal AG concentration was 21.8 micrograms/ml (SD = 5.9 micrograms/ml, range 9.6-38.8 micrograms/ml). This distribution of AG concentration was significantly different from that in patients with impaired glucose tolerance (IGT) (13.3 +/- 5.4 micrograms/ml) and definitely different from that in diabetic patients (2.1 +/- 1.8 micrograms/ml). In a standard glucagon test, it was suggested that the decrease of plasma AG was affected not only by glycemic control of the patients but also by pancreatic cell secretory activity. The reduction of AG concentration was more marked in IDDM patients than in NIDDM patients. In longitudinal studies, AG concentration was shown to be sensitive to glycemic control. However, its recovery showed a tendency toward much delay after the improvement of fasting blood glucose or HbA1 concentrations. On the other hand, AG concentration showed negligible diurnal change and no immediate change as a result of diet, oral glucose load, or acute shift of the insulin level in both normal and diabetic subjects.

Physiological conditions for the study of basal and meal stimulated exocrine pancreatic secretion in the dog. Absence of feedback inhibition of basal secretion.

Pancreatic secretion has been studied in dogs in basal and postprandial conditions, as nearly physiological as possible. When pancreatic juice was excluded from the duodenum pancreatic secretion was not raised, compared with secretion during the return of juice to the duodenum. In fact, in seven mongrels, returning pancreatic juice led a transient rise in pancreatic secretion. This was not seen in five beagles. These results indicate that dogs do not manifest the feedback control of pancreatic secretion by pancreatic juice observed in other species. Pancreatic secretory activity was determined in 10 dogs after stimulation by food. The highest secretion rates occurred during the initial 60 min. The maximal secretion of protein occurred before the maximal secretion of fluid and bicarbonate. The effect of the meal diminished slowly during the subsequent minutes but did not reach basal levels after 2 h. In physiological conditions, maximal pancreatic secretion of fluid and bicarbonate was about one-fifth and of protein was almost one-seventh of the maximal secretory capacity obtained with secretin and cholecystokinin, respectively. Potential specific activity of trypsinogen was unchanged during the different experimental conditions. Trypsinogen output represented a constant average of 20% of protein output. The interindividual variability of pancreatic secretion rates was reduced when outputs were expressed per kilogram of body weight. In general, a significant positive correlation was found between body weight and the secretory outputs. No differences were observed in the response of mongrel and beagle dogs to a meal.

Variation in canine exocrine pancreatic secretory activity during the interdigestive state.

Interdigestive changes in pancreatic volume flow, gastric motor activity, and intraduodenal pH were monitored automatically in eight dogs. As a result, two different periods of pancreatic secretion were found to occur alternately during the interdigestive state: one a secretory period (2.2 +/- 0.32 ml/10 min with high protein and low bicarbonate concentration) and the other a nonsecretory period. The secretory period corresponded to the interdigestive phase II and III contraction period in the stomach, and the nonsecretory period coincided with the motor quiescent period in the stomach. However, another secretory period was identified during the interdigestive state; it occurred when the intraduodenal pH went below 7.0, and no typical interdigestive contractions were observed in the stomach. The secretory rate was 3.7 +/- 0.33 ml/10 min and was low in protein and high in bicarbonate concentration. The present study demonstrates that basal pancreatic secretory activity is never uniform but fluctuates with motor events in the stomach. However, its control mechanism remains unknown at present.

Amines and the rat exocrine pancreas: (1) Effects of receptor blockers on turnover of L-dopa

The acinar cells of the exocrine pancreas have the capacity of efficiently take up and metabolize L-dopa. In the present study, the metabolism of L-dopa by the exocrine pancreas of the rat and effects of receptor blockers on the metabolism were studied by fluorescent histochemical and chemical methods. After i.v. administration of L-dopa (50 mg/kg), a large amount of dopamine (DA) was detected in the exocrine pancreas, and in the pancreatic juice large amounts of DA and its metabolites. DA-blockers (haloperidol, sulpiride, and pimozide) and α-blockers (phenoxybenzamine, and phentolamine) produced a significant increase in the accumulation of DA after administration of L-dopa. On the other hand, β-blockers (propranolol, and oxprenolol) were without effects. The excretion of DA into the pancreatic juice appeared to be associated with the secretion of zymogen granules, thus DA serves as an indicator of pancreatic secretory activity, especially of enzyme secretion. Because DA- and α-blockers produced an increase in the accumulation of DA, dopaminergic and/or α-adrenergic mechanisms probably exist in the exocrine pancreas of the rat and these mechanisms modify the enzyme secretion.

Amines and the rat exocrine pancreas: (1). Effects of receptor blockers on turnover of L-dopa.

The acinar cells of the exocrine pancreas have the capacity of efficiently take up and metabolize L-dopa. In the present study, the metabolism of L-dopa by the exocrine pancreas of the rat and effects of receptor blockers on the metabolism were studied by fluorescent histochemical and chemical methods. After i.v. administration of L-dopa (50 mg/kg), a large amount of dopamine (DA) was detected in the exocrine pancreas, and in the pancreatic juice large amounts of DA and its metabolites. DA-blockers (haloperidol, sulpiride, and pimozide) and alpha-blockers (phenoxybenzamine, and phentolamine) produced a significant increase in the accumulation of DA after administration of L-dopa. On the other hand, beta-blockers (propranolol, and oxprenolol) were without effects. The excretion of DA into the pancreatic juice appeared to be associated with the secretion of zymogen granules, thus DA serves as an indicator of pancreatic secretory activity, especially of enzyme secretion. Because DA- and alpha-blockers produced an increase in the accumulation of DA, dopaminergic and/or alpha-adrenergic mechanisms probably exist in the exocrine pancreas of the rat and these mechanisms modify the enzyme secretion.

Binding of secretin to plastic surfaces

Five carboxyl-terminal fragments of secretin ranging in size from 6 to 21 amino acid residues were tested for pancreatic secretory activity in the rat. None of the fragments displayed activity when given alone but each displayed significant activity when given after secretin. This apparent activity was shown to be the result of displacement of secretin bound to the walls of the injection catheter. The activity was abolished by dissolving secretin in 2% bovine serum albumin. The finding emphasizes the ease with which secretin can bind to plastic surfaces and consequently the need to reevaluate previous dose-response studies and the caution required in the design of future studies.

Pancreatic secretory activity of secretin5–27 and substituted analogues

The effect of secretin5–27 and four substituted analogues (9-Gln-secretin5–27, 15-Asn-secretin5–27, 9-Gln-15-Asn-secretin5–27, and 15-Lys-secretin5–27) on pancreatic secretion in the rat and guinea pig was examined. Secretin5–27 retained significant pancreatic secretory activity in both species. Its efficacy (intrinsic activity) relative to secretin was much higher in the rat (0.2) than in the guinea pig (0.03). The activity of secretin5–27 was not affected by a single or dual substitution of carboxylic acid residues by the corresponding carboxamides or by lysine despite a substantial decrease in the helical character of the peptide.

The inhibitory effect of barbituric acid on glucose- and tolbutamide-stimulated insulin secretion in the rat

The effects of barbituric acid (BA) on glycemic homeostasis in rats were investigated. Pretreatment with 200 mg/kg of BA attenuated tolbutamide-induced hypoglycemia and hyperinsulinemia. The same pretreatment reduced glucose tolerance without reducing serum insulin concentrations. However, evaluation of insulinogenic indices demonstrated differences in pancreatic insulin secretory activities. Intraperitoneally administered BA produced an initial hyperglycemia which was attributed to stress-related factors since the response was abolished by adrenalectomy. BA attenuation of tolbutamide-induced hypoglycemia was not blocked by adrenalectomy, which suggests an extra-adrenal site of action for BA. This extra-adrenal site of action appears to be the pancreatic β cell. Structural similarities between BA and other agents known to influence pancreatic insulin secretory activity suggest a possible competition for reactive binding sites on or within the pancreatic β cell.