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Biomedical subjects

I Lundquist

Publications and source records attributed to I Lundquist.

At least 163 records · Page 9Linked to original sources
PubMed1977

Protamine induced intracellular uptake of horseradish peroxidase and vacuolation in mouse skeletal muscle in vitro.

The uptake in vitro of horseradish peroxidase (HRP) in mouse skeletal muscle was examined by electron microscopy and chemical determination. In muscles exposed to an HRP solution for 60 min at +37 degrees C, HRP infiltrated the basal lamina of muscle fibres and caused an intense labelling of their sarcolemma. In addition HRP was found within the transverse tubules. Exposure to HRP for 30 min at +37 degrees C followed by HRP together with a polycationic protein (protamine) for 30 min at +37 degrees C caused an intracellular vesicular uptake of HRP. Intracellular HRP was found in numerous vesicles, membrane limited bodies and vacuoles. Protamine also induced focal autophagic vacuolation with progressive muscle fibre degeneration. An intracellular HRP uptake or muscle cell vacuolation could not be detected in the absence of protamine or when the incubation temperature was +4 degrees C. Chemical determination of HRP uptake was in general agreement with the morphological results. The uptake of HRP in the presence of protamine was stimulated at +37 degrees C and blocked at +4 degrees C. The results suggest that in skeletal muscle in vitro intracellular uptake of macromolecules occurs by endocytosis.

Animals↗
PubMed1977

Accumulation of dopamine in mouse pancreatic B-cells following injection of L-DOPA. Localization to secretory granules and inhibition of insulin secretion.

Accumulation and subcellular localization of dopamine (DA) in pancreatic B-cells and its effects on insulin secretion were investigated in mice following a single injection of L-3,4-dihydroxyphenylalanine (L-DOPA). Electron microscopic autoradiography showed that 3H-DA formed from administered 3H-DOPA was present over B-cells as well as over other types of islet cells. Pretreatment of the animals with a decarboxylase inhibitor greatly reduced the number of autoradiographic grains. In the B-cells the 3H-DA-grains were associated with the secretory granules. The location of the label may suggest an incorporation in the periphery of the beta-granule, rather than in the dense core, supposed to contain insulin. Accumulation of DA in the B-cells following L-DOPA administration was found to inhibit partially the insulin secretory response to different insulin secretagogues (glucose, glibenclamide and L-isopropylnoradrenaline (L-IPNA). Treatment with monoamine oxidase inhibitor + L-DOPA induced an almost total suppression of L-IPNA-stimulated insulin secretion, whereas glucose-induced insulin release was still only partially inhibited. Pretreatment with a decarboxylase inhibitor abolished the effects of L-DOPA. It is suggested that intracellularly accumulated DA in the B-cell exerts an inhibitory action on insulin releasing mechanisms induced by different secretagogues and that this action might involve interference with a calcium translocation process at the level of the secretory granule.

Animals↗
PubMed1977

Feedback regulation of pancreatic enzyme secretion by intestinal trypsin in man.

In a patient a papilla Vateri tumor completely prevented the bile-pancreatic flow into the intestine although the pancreatic juice was secreted into the bile duct via a common channel. Consequently, the bile-pancreatic juice was possible to sample via a percutaneous transhepatic cholangiography (PTC) catheter. This made it possible to study the effect of duodenal infusion of different substances on the bile-pancreatic secretion. In repeated experiments a suppression of the secretion was observed by intraduodenal trypsin as well as the patient's own bile-pancreatic juice. In the presence the bile-pancreatic juice intraduodenal trypsin inhibitor infusion caused a marked stimulation of the secretion. The results are in accordance with the hypothesis that trypsin in the upper part of the intestine exerts a negative feedback regulation of the pancreatic secretion in man.

Aged↗
PubMed1977

Pattern of islet lysosomal enzyme activities and insulin secretory response.

The pattern of lysosomal enzyme activities in isolated pancreatic islets was studied in 3 different strains of mice, NMRI, CBA, and C-57, and related to the in vivo insulin release following injection of the insulin scretagogues glucose and carbachol. It was observed that the relative specific activities among the islet enzymes studied did not show the same pattern in the different strains although beta-gluc-ronidase always displayed the lowest activity. Comparison between the strains revealed that acid phosphatase activity was of the same magnitude in all 3 strains. Islet activities of acid amyloglucosidase, beta-glucuronidase, and N-acetylglucosaminidase, however, were largest in NMRI, intermediate in CBA, and lowest in C-57. This activity pattern roughly correlated with the insulin secretory response to an intravenous injection of glucose, whereas insulin release induced by the cholinergic agonist carbachol was of similar magnitude in all strains.

Acetylglucosaminidase↗
PubMed1976

Direct calcium-stimulated release of glucagon from the isolation perfused rat pancreas and the effect of chemical sympathectomy.

"Staircase" increments of calcium (from 0.5 to 15 mEq/L) were added to the perfused rat pancreas in the absence of glucagon secretogogues. Large spikes of glucagon release resulted, particularly at the small and large calcium concentrations. Insulin secretion was undetectable. Selective destruction of peripheral adrenergic neurons by pretreatment of the rats with 6-hydroxydopamine reduced the basal glucagon secretion to about 50% and specifically suppressed the calcium-induced glucagon release at the lower calcium steps. The response to a subsequent stimulation by arginine/calcium was not inhibited. Results suggest that glucagon secretion is modulated by a stimulant effect of the pancreatic adrenergic nerves (norepinephrine?) and that calcium in part positively affects release by permitting this neural stimulation.

Animals↗
PubMed1976

Interaction of calcium and glucose on glucagon secretion.

The interrelationship between calcium ion and glucose on glucagon release was studied in the in vitro perfused pancreas. Spontaneous release during perfusion with glucose-free, calcium-depleted (0.2 mEq/l calcium) medium was completely abolished by ethylene glycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA; 0.2 mM). Glucose added to calcium-depleted perfusate caused only partial inhibition of glucagon release, even at concentrations of 500 mg/dl, and there was no evidence of a paradoxical increase in secretion with time. When calcium was added in a series of steps (in the absence of additional secretagogues) more than half of the increased glucagon released was elicited by the first step (0.5 mEq/l). Release patterns at subsequent steps suggested that higher concentrations of calcium may cause mixed stimulation and inhibition. With 70 mg/dl glucose, calcium-stimulated release was partially suppressed at all calcium concentrations up through 9 mEq/l. With 150 mg/dl glucose, addition of the normally stimulating 0.5 mEq/l calcium caused abrupt and complete inhibition of glucagon secretion, and this persisted at all higher calcium concentrations. Insulin release, when high enough to be detected, did not correlate with the glucose/calcium suppression of glucagon. In other experiments, control results and all insulin secretion patterns were qualitatively similar to those reported by other investigators; however, various attempts to demonstrate a paradoxical increase glucagon secretion by glucose during calcium deprivation were unsuccessful. It is concluded that small amounts of calcium are normally required for glucagon secretion, although at higher concentrations the effects become complex. In addition, glucagon suppression by glucose is calcium-requiring. Thus, changes in glucagon secretion caused by addition or depletion of calcium can depend on the relative amount of glucose in the milieu.

Animals↗
PubMed1976

Oral trypsin-inhibitor-induced improvement of the exocrine and endocrine pancreatic functions in alloxan diabetic rats.

Studies are presented dealing with the effect on the exocrine and endocrine pancreas of long-term oral trypsin inhibitor administration to alloxan diabetic rats. Three categories of rats were used: a) normal rats, b) alloxan diabetic rats, and c) alloxan diabetic rats treated with the trypsin inhibitor. 1. The concentration of amylase in both pancreas and intestinal contents were markedly decreased in alloxan diabetic rats as compared with normal rats, whereas the concentrations of lipase and trypsin(ogen) were practically unaffected by the diabetic state. 2. Trypsin inhibitor treatment of diabetic rats enhanced the concentrations of both amylase, trypsin(ogen), and lipase in pancreas and intestinal contents when compared with untreated diabetic controls. 3. Alloxan diabetic rats treated with trypsin inhibitor displayed an increased weight gain, increased pancreatic weight, and increased pancreatic protein concentration as compared with the untreated diabetic controls. 4. Alloxan diabetic rats treated for 3 or 5 weeks with the trypsin inhibitor were found to have decreased basal blood glucose levels and an increased plasma insulin: blood glucose ratio as compared to the untreated diabetic controls. 5. There was no apparent difference in the glucose elimination rate after I.V. glucose loads in diabetic rats given trypsin inhibitor and their diabetic controls. However, the insulin secretory response to the glucose stimulus was slightly improved in the trypsin inhibitor group. 6. Alloxan diabetic rats treated with trypsin inhibitor had an increased total pancreatic insulin content compared with their diabetic controls. It is concluded that long-term daily treatment with oral trypsin inhibitor in alloxan diabetic rats increased enzyme production and secretion in the exocrine pancreas, and produced an improvement of the diabetic condition of the animals. This improvement might partly be due to an increased pancreatic content and secretion of insulin.

Amylases↗
PubMed1976

Effects on exocrine and endocrine rat pancreas of long-term administration of CCK-PZ (cholecystokinin-pancreozymin) or synthetic octapeptide - CCK-PZ.

Studies are presented dealing with the effects on exocrine and endocrine rat pancreas of repeated subcutaneous injections for 10 days of equivalent doses (Ivy dog units) of commercial (10% pure) cholecystokinin-pancreozymin (CCK-PZ) and of the synthetic C-terminal octapeptide of CCK-PZ. Both rats treated with the commercial CCK-PZ and the octapeptide had an increase wet weight of the pancreas. Pancreatic concentrations of amylase, lipase, and trypsinogen increased in a parallel fashion after both kinds of hormonal treatment. Rats given the 10-day treatment with the commercial CCK-PZ preparation displayed a lower insulin response following an intravenous glucose load. The glucose tolerance, however, was slightly improved. The octapeptide treatment induced no alterations of the insulin or glucose levels after similar glucose loads. The insulin content and the concentration of protein in pancreatic tissue or glycogen in liver and muscle tissue were unaffected by both ways of treatment. Likewise no difference was found on glucose utilization in muscle tissue in vitro. It is concluded that equipotent doses of the synthetic octapeptide and the 10% pure CCK-PZ preparation induce a similar and parallel increase of the concentration of all three exocrine pancreatic enzymes. The inhibitory effect on glucose-induced insulin release exerted by the 10-day treatment with commercial CCK-PZ but not by the octapeptide is conceivably due to peptide impurities in the commercial CCK-PZ and/or to parts of the CCK-Pz molecule other than the C-terminal octapeptide.

Amylases↗
PubMed1976

Carbohydrate metabolism in normal and diabetic rats following long-term oral trypsin inhibitor administration.

The effect of long-term oral trypsin inhibitor administration on blood glucose, plasma insulin, liver, and muscle glycogen and glucose utilization in vitro by peripheral tissues in normal and diabetic rats was studied. In normal rats the glycogen levels in liver and muscle were increased after 3 weeks of treatment. Glucose oxidation (14CO2-production) was augmented in muscle after 3 and 8 weeks and in liver after 3 weeks. An increased 14C-incorporation into glycogen from 14C-glucose and increased glycogen concentration after incubation were found in muscle after 3 weeks. In diabetic rats the basal blood glucose was decreased after 3 and 5 weeks of treatment, and the basal plasma insulin:blood glucose ratio increased after 5 weeks. The glycogen levels were increased after 3 and 5 weeks in liver. No effect on glucose oxidation (14CO2-production) in muscle was found. The 14C-incorporation into glycogen and the total glycogen content, however, was increased in muscle after both 3 and 5 weeks. Incubation of muscle tissue with serum from normal or diabetic rats treated with oral trypsin inhibitor for 3 and 5 weeks respectively had no apparent acute effects on the glucose metabolism. It is suggested that the observed action of oral trypsin inhibitors on glucose metabolism in peripheral tissues is mediated by one or more unknown gastrointestinal factor(s).

Administration, Oral↗
PubMed1975

Effect of vinblastine in vivo on ultrastructure and insulin releasing capacity of the B-cell following sulphonylurea and isopropyl-noradrenaline.

The effect of vinblastine in vivo on ultrastructure and insulin releasing capacity of the B-cell was studied in mice. Treatment with vinblastine (1.1 mumole/mouse) resulted in a 75% decrease of the amount of normal microtubules and the appearance of characteristic paracrystals. Basal plasma immunoreactive insulin levels were depressed to about 60% of the control level. The dose-response pattern for insulin release (first phase) following two chemically unrelated insulin secretagogues, the potent sulphonyl-urea derivative, glibenclamide, and the beta-adrenegic agonist L-isopropylnoradrenaline, (L-IPNA), was tested with and without vinblastine pretreatment. The dose-response curves for L-IPNA-induced insulin release in vinblastine-treated and control animals did not deviate significantly from each other, whereas insulin release following glibenclamide was almost totally suppressed by vinblastine except at the lowest dose level. Injection of maximal doses of glibenclamide or L-IPNA did not alter the ultrastructural changes induced by vinblastine in the B-cells. It is suggested that the microtubular system of the B-cell might play a minor role for certain insulin-releasing processes and/or that vinblastine might have other important effects on the insulin secretory machinery.

Animals↗
PubMed1975

Carbohydrate content and regulation following injection of different glycogenolytic enzymes.

The effect of injection of glycogenolytic enzymes on tissue glycogen, blood glucose and plasma insulin was studied in mice. No effects were observed following phosphorylase, whereas the hydrolytic enzymes, alpha-amylase and acid amyloglucosidase depressed liver glycogen. In addition acid amyloglucosidase induced a decrease in blood glucose, a slight elevation of plasma insulin and a marked increase in tolbutamide-stimulated insulin release. At the doses given none of the enzymes affected muscle glycogen. Amyloglucosidase pretreatment markedly enhanced insulin release induced by glibenclamide, leucine, isoleucine, lysine and glucose whereas insulin release stimulated by IPNA, ACTH, glucagon and "CCK-PZ" was unaffected. Injection of acid amyloglucosidase has a profound influence on carbohydrate content and regulation in mice. It is suggested that the dependence or independence of amyloglucosidase activity among the insulin secretagogues tested might reflect different or partially different mechanisms in the process of insulin secretion.

Adrenocorticotropic Hormone↗
PubMed1975

Interrelationships between alpha and beta-anomers of glucose affecting both insulin and glucagon secretion in the perfused rat pancreas. II.

Temporal and quantitative relationships between the alpha and beta anomers of glucose on insulin and glucagon secretion were studied in two surgical preparations of the in vitro perfused rat pancreas. Alpha-Glucose was a more effective stimulator of insulin release. Beta-Glucose, however, though less effective, was a positive modulator when admixed with alpha-glucose. Dose-response studies showed that alpha-glucose probably had a smaller apparent Km for insulin secretion, while the Vmax for the two anomers was the same-the effects of the two anomers being indistinguishable at high glucose concentrations (300 mg/dl). Alpha-Anomeric stereospecificity was demonstrable equally on both phases of insulin release and was maintained throughout 60-min perfusions. Spontaneous or arginine-stimulated glucagon release was also preferentially inhibited by alpha-glucose. Since others have shown that glucose uptake and phosphorylation in islets are not alpha-stereospecific, the data suggest that the initial signal for the first and second phases of insuulin release and glucose suppression of glucagon secretion is at the level of a glucoreceptor prior to, or indedendent of, major pathways of glucose metabolism.

Animals↗
PubMed1975

Differential changes in the 5-hydroxytryptamine and insulin content of guinea-pig B-cells.

In the guinea-pig pancreas, 5-hydroxy-tryptamine (5-HT) occurs in the B-cells as well as in enterochromaffin cells scattered in the exocrine parenchyma. In the present study we examined the effects on the pancreatic 5-HT and insulin content of drugs known to affect the B-cells. For this purpose a radioimmunoassay of guinea-pig insulin was developed. Streptozotocin reduced the number of detectable B-cells and partially degranulated those that remained. It also lowered the insulin content of the pancreas and the 5-HT content of the B-cells but did not affect the 5-HT content of the enterochromaffin cells. Reserpine lowered the 5-HT content of both B-cells and enterochromaffin cells. The number and ultrastructure of the B-cells and the pancreatic insulin content was not affected. Streptozotocin + reserpine seemed to have additive effects of B-cell 5-HT. The results with these 2 drugs indicate that roughly 50% of pancreatic 5-HT is contained in the B-cells. Diazoxide markedly increased the pancreatic insulin content without affecting pancreatic 5-HT. Despite the fact that 5-HT and insulin are stored together in the cytoplasmic granules of the B-cells, 5-HT was differentially depleted from this store by reserpine. A marked disproportionality between 5-HT and insulin content was also induced by diazoxide.

Animals↗
PubMed1975

Portal and pancreatic vein catheterization with radioimmunologic determination of insulin.

Percutaneous transhepatic catheterization of the portal vein along with the catheterization of the aorta and the vena cava was performed in six patients, one of whom had hypoglycemic attacks due to Whipple's triad. Blood samples from different branches in the different vessel systems were withdrawn for radioimmunologic determination of insulin. By this method, preoperative localization of the insulin producing pancreatic islet cell tumor was su-cessfully performed. Multiple tumors as well as liver metastases were preoperatively excluded. Recatheterization and blood sampling for radioimmunologic determination of insulin was performed postoperatively to verify the radicality of the operation. Insulin concentrations from the hypoglycemic patients were compared with those of the patients without insulinoma and found to be significantly higher. The procedure is proposed as a useful method for localizing all types of gastrointestinal hormone producing primary or secondary tumors in which a method for hormone determination is available. The postoperative investigation is useful as a check of the operation performed and as a follow-up examination for the early diagnosis of recurrence.

Adenoma, Islet Cell↗
PubMed1975

Studies on the reversibility of oral trypsin inhibitor induced changes of rat pancreatic exocrine enzyme activity and insulin secretory capacity.

Rats were given a daily dose of bovine trypsin inhibitor for 3 weeks (Group 3 A) or 8 weeks (Group 8 A) via an orogastric tube. In another rat group the trypsin inhibitor after 3 weeks was replaced by water for another 5 weeks (Group 8 B). In group 3 A and 8 A an enlargement of the pancreatic gland was found. In group 3 A and 8A the pancreatic protein was increased. In group 3 A and 8 A the pancreatic trypsinogen increased in a more pronounced way than the amylase, while the pancreatic lipase was found to be uninfluenced by the trypsin inhibitor treatment. Five weeks after the cessation of a 3-week treatment the only remaining effect on the exocrine pancreas was an increase of the pancreatic trypsinogen. In group 3A an impairment of insulin secretion following intravenous L-isopropylnoradrenaline and glibenclamide was found. Glucose levels were similar to those of the control rats. Furthermore, a slight decrease of the pancreatic insulin content per g protein was found in these rats. In group 8A and 8B, the insulin secretory pattern was found to be normal following intravenous glucose administration, and an increased glucose elimination rate (k-value) compared with the control group suggested a favourable effect of oral trypsin inhibitor treatment on the glucose tolerance,

Administration, Oral↗