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Biomedical subjects

C Kühl

Publications and source records attributed to C Kühl.

At least 109 records · Page 6Linked to original sources

Secretory effects of secretin on isolated perfused porcine pancreas.

The effect of pure natural porcine secretin on endocrine and exocrine pancreatic secretion was studied in the totally isolated perfused porcine pancreas. The exocrine pancreatic responses to secretin correspond well with those obtained in the anesthetized pig. The lowest concentration of secretin observed to increase pancreatic secretion was 2.8 pmol/liter, whereas the maximum pancreatic responses were obtained at a secretin concentration of 92 pmol/liter. The infusion of secretin in concentrations ranging from 2.8 to 278 pmol/liter in the presence of a constant concentration of glucose (7.5, 5.0, or 3.5 mmol/liter) was without effect on the insulin and glucagon release. Infusion of secretin at a concentration of 834 pmol/liter in the presence of glucose at 7.5 mmol/liter provoked a significant (P less than 0.01) short-lived increase in insulin secretion. However, there was no effect on the glucagon secretion. The results of this study indicate that neither the augmented insulin response nor the suppression of glucagon elicited by oral glucose depend on secretin.

Animals↗

Effects of oral phenylalanine load on plasma glucagon, insulin, amino acid and glucose concentrations in man.

An oral phenylalanine load provokes a significant drop in serum tyrosine levels in children with phenylketonuria [8]. The aim of the present investigation was to examine the response of insulin and glucagon to oral phenylalanine loading as these hormones are known to have a hypoaminoacidaemic effect. Six adult normal weight and healthy men were loaded orally with 0.6 mmol L-phenylalanine per kg body weight after an overnight fast. Serum phenylalanine increased within 10 min after the load and reached a maximum concentration at 30 min. Serum tyrosine increased within 10 min after the load and reached a maximum concentration at 2 h. Plasma glucagon and insulin increased during the first 10 min after the load and reached a peak twice the fasting levels at 30 min after the load. The molar insulin/glucagon ratio remained unchanged during the first 20 min after the load but then declined by 50% at 2 h. Associated with this decline plasma amino acid concentration (except phenylalanine and tyrosine) declined by approximately 15%. The decline was most marked for isoleucine, leucine, methionine and valine. As the hypoaminoacidaemic effect of insulin and glucagon is known to be most marked for these four amino acids plus phenylalanine and tyrosine, the response of insulin and glucagon to a phenylalanine load may influence not only the fate of phenylalanine given but also the blood tyrosine level.

Administration, Oral↗

Localization of insulinomas and islet cell hyperplasias by pancreatic vein catheterization and insulin assay.

Percutaneous transhepatic portal vein catheterization and transfemoral portal and caval catheterizations were performed under local anesthesia in five patients with symptoms of organic hypoglycemia. During the investigation, results of pancreatic phlebography revealed the pancreatic venous anatomy. Blood obtained from the celiac artery, caval branches and pancreatic veins was assayed for insulin by two different radioimmunoassay methods. Pathologically high, pancreatic arteriovenous insulin differences in two patients with insulinomas and in two patients with islet cell hyperplasia. In one of the patients with an insulinoma, one of the assays failed to detect the tumor insulin. This inconsistency still remains unexplained. Angiography revealed a pancreatic abnormality in only two patients. During operation, two of the tumors were found upon palpation and inspection. Pancreatic resections were performed according to the findings of pathologic hormone differences in all five patients. Immunocytochemistry revealed that three of the patients had insulin-producing tumors and two had local islet cell hyperplasia. Catheterizations performed two months postoperatively confirmed the radicality of the operation in all patients, with the possible exception of one patient. In one patient, a recurrance was detected by catheterization ten months postoperatively.

Adenoma, Islet Cell↗

Pancreatic somatostatinoma. Clinical features and physiological implications.

The first case of a tumour producing somatostatin-like immunoreactivity and bioactivity is presented. The pancreatic tumour was composed of cells indistinguishable from islet D cells. Radioimmunoassay of blood-samples obtained by tumour-vein catheterisation revealed very high levels of somatostatin immunoreactivity. On gel chromatography tumour extracts were found to contain at least 4 different immunoreactive components, one of which eluted in the position of synthetic somatostatin. Extracts from the tumour were potent in inhibiting insulin and glucagon secretion from isolated perfused porcine pancreas. Clinical abnormalities included hypochlorhydria, steatorrhoea, and diabetic glucose tolerance. Conceivably some of these abnormalities may be related to somatostatin hypersecretion from the pancreatic tumour.

Antigen-Antibody Reactions↗

Islet cell hyperplasia localized by pancreatic vein catheterization and insulin radioimmunoassay.

A patient with organic hypoglycemia but with normal pancreatic arteriography was investigated with pancreatic vein catheterization for insulin immunoassay. Very high insulin concentrations (1, 130 micronU/ml) were found in a vein draining part of the pancreatic tail. Even though no tumor was found at operation, distal hemipancreatectomy was performed according to the assay findings. Histology and immunohistochemistry revealed a localized islet hyperplasia.

Adult↗

Effect of pregnancy on the glucagon response to protein ingestion.

Plasma glucose, insulin and glucagon concentrations were measured before and after the ingestion of a protein-rich meal in 11 healthy pregnant women in the last trimester of pregnancy, and again in the same subjects postpartum. Compared to postpartum, basal levels of plasma glucose were lower in late pregnancy whereas basal insulin and glucagon concentrations were both enhanced. After the meal, insulin and glucagon concentrations in plasma increased in gestation as well as postpartum. Plasma glucose increased slightly in pregnancy but remained unchanged postpartum. The mean insulin response to the meal was unaffected by pregnancy whereas that of glucagon was reduced. Thus following protein ingestion, plasma glucose rose in pregnancy in spite of unchanged levels of insulin and depressed levels of glucagon. Favouring analbolism, the reduced glucagon response to protein ingestion in pregnancy fits in the concept of 'facilitated anabolism' in late pregnancy and, moreover, it lend further support to the idea that changes in glucagon secretion per se are not involved in the pathogenesis of the diabetogenicity of pregnancy.

Blood Glucose↗

Serum proinsulin in normal and gestational diabetic pregnancy.

The concentration of proinsulin-like components (PLC) in serum has been determined by gel filtration on samples obtained from eight normal pregnant women and eight nonobese gestational diabetics. The normal women were investigated early in pregnancy and all subjects were investigated in mid pregnancy, late pregnancy, and postpartum. At each occasion, samples were obtained after an overnight fast and after glucose ingestion. In both groups, the concentration of PLC in serum after overnight fast rose with gestation as well as after glucose ingestion, but there were no significant differences between mean levels of PLC of the normals and the gestational diabetics. With gestation, serum insulin rose in parallel with PLC in either group. The proportion of total insulin immunoreactivity composed by PLC thus remained constant and, furthermore, the proportions of PLC in gestation were equal to those observed postpartum. Four to six weeks after delivery, the basal concentration of PLC in serum was higher in the gestational diabetics than in the normals, whereas the concentrations of insulin were equal. Since the biological potency of proinsulin is much less than that of insulin, the results exclude the possibility that the decrease of glucose tolerance in normal pregnant women and gestational diabetics is due to an increased concentration of proinsulin in serum.

Adult↗

The enteral insulin-stimulation after pancreas transplantation in the pig.

The insulin responses to an oral glucose tolerance test (OGTT) and in intravenous glucose infusion (IVGI), designed to copy the changes in serum glucose concentrations found during OGTT, were measured in four pigs before and after heterotopic pancreatico-duodenal allotransplantation and total pancreatectomy. After transplantation and total pancreatectomy a remarkable hyperinsulinaemia occurred during OGTT and IVGI, reflected by an almost two-fold increment in the insulinogenic index after transplantation. This finding might be explained by drainage of the transplanted pancreas into the systemic circulation instead of the portal vein. The magnitude of the enteral stimulus, i. e. the incretin effect on insulin secretion during OGTT was unchanged after transplantation, suggesting that the incretin effect is not mediated by neural influences upon the endocrine pancreas.

Administration, Oral↗

Plasma insulin concentration during physiological variations in immunoreactive plasma secretin.

The effect of endogenous and exogenous secretin on fasting plasma insulin and glucose concentrations in peripheral venous blood was studied. In 10 non-diabetic subjects intragastric instillation of 300 ml 0.1 mol/l hydrochloric acid increased the plasma secretin concentration significantly. This increment did not influence insulin or glucose concentration. Control experiments with intragastric instillation of 300 ml of isotonic saline did not influence the plasma concentration of secretin, insulin or glucose. In four other non-diabetic persons no significant changes were found in plasma insulin or glucose concentration during an i.v. infusion of pure natural porcine secretin in doses of 0.1, 0.3, 1.0 and 3.0 clinical units/kg/h. The results suggest that secretin is without effect on insulin secretion in the fasting normal subject.

Adult↗

Serum glucose determination with dextrostix and the eyetone reflectance meter.

A simple, modified procedure for the Dextrostix-Eyetone system has been evaluated in order to enable the system to measure the concentration of glucose in serum as well as in whole blood. A reduction of the ordinary time of reaction on the Dextrostix from 60 to 45 sec gave serum glucose determinations by the Dextrostix-Eyetone system that correlated almost perfectly with those obtained by a specific conventional laboratory procedure. Thus, the coefficient of correlation was 0.99 and the regression line very close to the ideal line. As the modification is very simple and does not involve any changes in the adjustment of the instrument, it is recommendable in all cases where only serum samples are available.

Blood Glucose↗

Porcine gastric insulin.

We recently found that plasma from pancreatectomized pigs contained concentrations of insulin of 5-10 muU/ml up to five days after pancreatectomy. In search of an extrapancreatic source of insulin, acid-ethanol extracts of porcine stomach and small bowel mucosa were investigated for the presence of insulin. The extracts of the stomach contained large amounts of insulin immunoreactivity while insulin was not detectable in extracts of the small bowel. Upon gel filtration, immunoreactive insulin eluted from the gastric mucosa in a major peak corresponding to the elution volume of an insulin standard and a minor peak corresponding to the elution volume of a proinsulin standard.

Animals↗

Effect of ethanol on the glucose-mediated insulin release in triply catheterized anesthetized pigs.

In order to further elucidate the potentiating effect of ethanol on the glucose-mediated insulin response, triply catheterized anesthetized pigs were submitted to an intravenous glucose infusion test after a four-hour preinfusion with ethanol (11 pigs) or saline (six pigs, control experiment). During the tests portal, hepatic, and peripheral venous blood was drawn simultaneously. Two series of ethanol-preinfusion experiments were carried out: in one series the serum ethanol concentration was maintained at approximately 10 mM and in the other at 19 mM. Compared with saline, 10 mM of serum ethanol induced a more than threefold increment in the insulin secretory response to glucose as estimated in the portal blood (p less than 0.01). Likewise, hepatic and peripheral venous blood insulin levels were enhanced (p less than 0.01). In contrast, 19 mM of serum ethanol did not elevate serum insulin levels above those found in the control experiments. When individual incremental portal insulin areas were plotted against the corresponding average value of serum ethanol in the preinfusion period, a significant inverse relationship was found (p less than 0.02), indicating a decrease in the potentiating effect of ethanol on the glucose-mediated insulin response with increasing levels of serum ethanol. Comparison of portal and hepatic incremental insulin areas revealed that ethanol did not, in the concentration range investigated, influence the hepatic insulin degradation rate. In conclusion, ethanol seems to potentiate, in an inverse concentration-dependent manner, the glucose-mediated insulin response through an action directly on the pancreas.

Animals↗

Influence of basal plasma glucose concentration on the glucagon response to arginine.

Plasma glucose and glucagon concentrations were measured in the portal vein of six healthy, anaesthetized pigs submitted to an intravenous arginine infusion test. A monophasic glucagon response was observed in all pigs, the peak glucagon value being reached within an average of 5 minutes after the beginning of the infusion. The glucagon response, expressed as the incremental area below the hormone concentration curve, correlated inversely with the plasma glucose concentration before the start of arginine infusion (r=0.78) (p less than 0.05) indicating that glucose is a potent inhibitor of arginine-induced glucagon secretion in pigs.

Animals↗

Isolation and perfusion of the porcine pancreas.

The isolation of a porcine pancreas preparation without the attached duodenum is described. The preparation is suitable for study of the secretion of insulin and pancreatic glucagon. The surgical procedure by which the pancreas is removed from tha animal is decribed as well as the perfusion system. The effect of various concentrations of glucose (63, 90, 135 and 180 mg per 100 ml) in the perfusion medium on the secretion of insulin and pancreatic glucagon was investigated in order to observe the performance characteristics of this preparation. Increasing concentrations of glucose caused a significantly greater insulin release, whereas the glucagon response was significantly reduced.

Animals↗

The enteroglucagon response to intrajejunal infusion of glucose, triglycerides, and sodium chloride, and its relation to jejunal inhibition of gastric acid secretion in man.

In a previous communication we demonstrated that pentagastrin-induced gastric acid secretion is strongly and equally inhibited by intrajejunal infusions of hypertonic glucose, hypertonic sodium chloride, and triglycerides. Samples of peripheral venous blood obtained during these experiments were now analysed for insulin, glucose, pancreatic glucagon, and enteroglucagon. Pancreatic glucagon was stimulated weakly only by triglycerides. Enteroglucagon secretion was strongly stimulated by glucose, moderately by triglycerides, and unaltered after sodium chloride. Insulin secretion was stimulated only during the glucose infusion. We concluded that enteroglucagon is not responsible for the jejunal inhibition of gastric acid secretion in man by jejunal administration of hyperosmolal NaCl solution but may participate in the inhbition evoked by jejunal administration of glucose of triglycerides. Furthermore, it is unlikely that enteroglucagon is in itself insulinogenic in man.

Adult↗

The effect of experimental heterotopic pancreatic allotransplantation on the insulin response to oral glucose administration.

Oral glucose tolerance tests (OGTT) were performed in 6 healthly, unimmunosuppressed pigs before and after heterotopic pancreatic transplantation and total pancreatectomy. Mean survival time after grafting was 55 days. Mean basal concentrations of glucose and insulin in serum were significantly higher after grafting and total pancreatectomy (p less than 0.01), but the insulin-to-glucose ratio was unaffected. The tolerance to oral glucose decreased after grafting and total pancreatectomy (p less than 0.01), even though the insulin levels in serum during OGTT were higher tp less than 0.01). This finding was also reflected in the insulinogenic index, which was almost twice as large after transplantation (p less than 0.01) as before. The decreased oral glucose tolerance might be explained by drainage of the transplanted pancreas into the systemic circulation instead of the portal vein.

Administration, Oral↗