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Biomedical subjects

I Lundquist

Publications and source records attributed to I Lundquist.

At least 109 records · Page 6Linked to original sources
PubMed1983

Hormonal and cholinergic influences on pancreatic lysosomal and digestive enzymes in rats.

Hormonal and cholinergic influences on lysosomal and digestive enzyme activities in pancreatic tissue were studied in normal adult rats. Hormonal stimulation by the cholecystokinin analogue, caerulein, induced a marked enhancement of the activities of cathepsin D and N-acetyl-beta-D-glucosaminidase in pancreatic tissue, whereas the activities of amylase and lipase tended to decrease. Acid phosphatase activity was not affected. Further, caerulein was found to induce a significant increase of cathepsin D output in bile-pancreatic juice. This output largely parallelled that of amylase. Cholinergic stimulation by the muscarinic agonist carbachol, at a dose level giving the same output of amylase as caerulein, did not affect pancreatic activities of cathepsin D and N-acetyl-beta-D-glucosaminidase. Further, cholinergic stimulation induced an increase of amylase activity and a slight decrease of acid phosphatase activity in pancreatic tissue. Lipase activity was not affected. No apparent effect on cathepsin D output in bile-pancreatic juice was encountered after cholinergic stimulation. The activities of neither the digestive nor the lysosomal enzymes were influenced by the administration of secretin. The results suggest a possible lysosomal involvement in caerulein-induced secretion and/or inactivation of pancreatic digestive enzymes, whereas cholinergic stimulation seems to act through different mechanisms.

Acetylglucosaminidase↗
PubMed1983

Influence of dietary fiber on exocrine pancreatic function in the rat.

Dietary fiber inhibits pancreatic enzyme activity--i.e., trypsin, lipase and amylase--in buffer solutions and in human duodenal juice in vitro. It is well established that oral administration of trypsin inhibitor stimulates the secretion and growth of the rat pancreas. In the present study, trypsin inhibitor (Trasylol) as well as dietary fiber such as pectin of low (37%) methoxylic esterification and wheat bran were found to stimulate pancreatic enzyme secretion in acute experiments in conscious rats with bile-pancreatic fistulae. Feeding for 10 days with wheat bran resulted in increased pancreatic weight and in increased protein and trypsinogen content. Administration of pectin of high (73%) methylic esterification caused increased pancreatic protein content and that of low methylic esterification increased pancreatic trypsinogen activity/milligram tissue. The results suggest that pectin and wheat bran may interfere with the feedback regulation of pancreatic enzyme secretion exerted by intraluminal trypsin, and, like trypsin inhibitor, have a secretagogue and trophic effect on the pancreas.

Amylases↗
PubMed1983

Interaction of gastric inhibitory polypeptide (GIP) and cholecystokinin (CCK-8) with basal and stimulated insulin secretion in mice.

The interaction of GIP and CCK-8 with basal insulin secretion and with insulin release induced by glucose or by the beta-adrenoceptor agonist L-isopropylnoradrenaline (L-IPNA) was studied in mice. GIP and CCK-8, when injected in threshold doses not affecting basal insulin secretion, did markedly enhance basal insulin release when given simultaneously. Maximal doses of the two peptides, on the other hand, did not potentiate each other's action, but displayed a pure additive effect on insulin secretion. Insulin release induced by a half-maximal dose of glucose was slightly potentiated by the threshold dose of GIP and markedly potentiated by the maximal dose i.e. the effect was greater than the algebraic sum of the individual actions. CCK-8 was without potentiating effect at both dose levels. The combination of GIP and CCK-8 did not display the potentiating effect of GIP alone on glucose-stimulated insulin release. However, an additive action was observed at both dose levels. Insulin release stimulated by a half-maximal dose of L-IPNA was not affected by either GIP or CCK-8 at the threshold doses. The combination of the two peptides and L-IPNA, however, displayed a lower response than that expected from an additive effect. Similarly, at the high dose level of the peptides, the combination of GIP plus CCK-8 and L-IPNA as well as CCK-8 alone plus L-IPNA displayed a lower insulin response than that expected from an additive effect. GIP alone plus L-IPNA gave the expected additive effect. The results show that interactions between different gastrointestinal polypeptides with insulin release may greatly change the expected effect exerted by any individually tested peptide, and that the action of the peptides on stimulated insulin secretion is highly dependent on the nature of the secretagogue. Such complex interactions must be borne in mind in the search for the incretin factor(s).

Adrenergic beta-Agonists↗
PubMed1983

Effects of pectin on glycaemia and insulinaemia after starch loading in normal, alloxan diabetic, and pancreatic duct-occluded rats.

In normal rats, and in rats with reduced intraluminal amylolytic activity, acute administration of low methoxyl pectin with soluble starch via an oro-gastric tube was found to delay starch digestion. In normal rats pectin slightly lowered plasma glucose levels after a starch load. In pancreatic duct-occluded rats, in which intestinal pancreatic digestive enzyme activities are markedly reduced, an increased insulin secretion and a reduced glucose response were seen after starch loading even without the addition of pectin, when compared to normal control rats. In these duct-occluded rats pectin was found to further reduce starch digestion, and markedly suppress plasma glucose levels after a starch load without changing plasma insulin levels. In moderately alloxan diabetic rats, in which intestinal amylase activity also was substantially reduced, pectin reduced the glucose response to starch to a similar extent (about 30%) as in duct-occluded rats without changing the impaired insulin response. The results suggest that pancreatic insufficiency accompanied by reduced intraluminal activities of pancreatic digestive enzyme activities may be associated with a decreased glucose and an increased insulin response to starch loading and that the ability of dietary fibre to reduce postprandial glycaemia may, inter alia, involve an inhibiting action by fibre on starch digestion, especially manifested in conditions of amylolytic insufficiency.

Amylases↗
PubMed1982

Interaction of vasoactive intestinal peptide (VIP) with cholinergic stimulation of glucagon secretion.

VIP-containing nerve fibers as well as cholinergic nerve fibers have a ubiquitous distribution in the body and both types of nerves have been demonstrated to innervate the pancreatic islets. The present study shows, in the intact, conscious mouse, that VIP and the cholinergic agonist carbachol stimulate glucagon secretion in a dose-dependent manner. Furthermore VIP and carbachol were found to exert potentiating interactions on glucagon secretion. These results suggest the existence of an interactive neural regulation of glucagon secretion, exerted by acetylcholine and VIP.

Animals↗
PubMed1982

Improved effect of glibenclamide on administration before breakfast.

In an attempt to assess whether intake of glibenclamide before meals would improve its therapeutic capacity, the present investigation compared the effect of glibenclamide 2.5 mg t.i.d. given before and together with meals. In addition, these effects were compared with that of glibenclamide given as a single morning dose of 7.5 mg. The subjects studied were six Type 2 diabetics not previously exposed to sulphonylurea drugs. Irrespective of dosage and mode of administration, addition of glibenclamide to a standardized breakfast, lunch and dinner enhanced plasma IRI concentrations and reduced blood glucose concentrations as compared to administration of meals without the drug. The different modes of glibenclamide administration did not differ significantly with respect to IRI responses. However the blood glucose reduction after breakfast was significantly greater when glibenclamide 2.5 mg had been given before the meal than when 2.5 or 7.5 mg were given with the meal; a similar, but non-significant tendency was observed after lung; no consistent difference was seen after dinner. Food intake did not affect glibenclamide kinetics. It appears that administration of glibenclamide 2.5 mg before breakfast improved glucose utilization following the breakfast load, due to earlier attainment of an effective concentration of glibenclamide.

Adult↗
PubMed1982

Influences of gastro-intestinal polypeptides and glucose on glucagon secretion induced by cholinergic stimulation.

UNLABELLED: Glucagon secretion from the endocrine pancreas is known to be enhanced by cholinergic stimulation. It has previously been described that vasoactive intestinal polypeptide (VIP) is a potent potentiator of this cholinergically induced glucagon secretion. In the present study, the effects of several gastro-entero-pancreatic polypeptides and glucose on glucagon secretion induced by the cholinergic agonist carbachol were investigated in vivo in the mouse. Carbachol was injected i.v. and it stimulated glucagon secretion. The polypeptides neurotensin and gastric inhibitory polypeptide (GIP) were both found to potentiate the carbachol-induced glucagon secretion, whereas substance P, pancreatic polypeptide, and two different molecular variants of cholecystokinin, CCK-8 and CCK-39, were without effect on cholinergically induced glucagon secretion. Neither of these polypeptides had any influence on basal glucagon secretion when tested over a wide dose range. Somatostatin and glucose both markedly inhibited carbachol-induced glucagon secretion. IN CONCLUSION: carbachol is a potent stimulator of glucagon secretion. This cholinergically induced glucagon secretion can be modified by several gastro-entero-pancreatic hormones influencing the release process both in potentiating and inhibiting direction. The physiological relevance of these interactions remains to be further investigated.

Animals↗
PubMed1982

Enhancement of insulin secretion during selective blockade of alpha 1- and alpha 2-adrenoceptors in the rat: effects of somatostatin.

The effects of somatostatin on plasma concentrations of insulin and glucose in the presence of the selective alpha 1-adrenoceptor blocking agent prazosin or the selective alpha 2-adrenoceptor blocking drug yohimbine were studied in vivo in anesthetized rats. Infusion of both prazosin (0.080 mg/min) and yohimbine (0.018 mg/min) increased plasma insulin levels within 10 min. Prazosin, but not yohimbine, caused a significant increment in plasma glucose concentrations during the infusion of both prazosin and yohimbine, suggesting that the inhibitory effect of somatostatin is not mediated via a direct action on alpha 1- or alpha 2-adrenoceptors. Plasma glucose concentration fell slightly during somatostatin administration. A marked increment in insulin release occurred in response to cessation of the somatostatin infusion, both during prazosin- and yohimbine-treatment. We conclude that somatostatin efficiently inhibits insulin secretion during selective alpha 1- and alpha 2-adrenoceptor blockade and, further, that the insulin off-response after somatostatin treatment is potentiated by alpha-adrenoceptor blockade. This study also indicates that blockade of alpha 1- as well as alpha 2-adrenoceptors leads to an increased insulin secretion.

Adrenergic alpha-Antagonists↗
PubMed1982

Cholinergic muscarinic effects on insulin release in mice.

Insulin secretion and blood glucose homeostasis were studied in mice following administration of cholinergic agonists, antagonists and other possible modifiers of cholinergic insulin secretory mechanisms. It was observed that administration to mice of the cholinergic agonists acetylcholine, carbachol and pilocarpine resulted in an increase in plasma immuno-reactive insulin levels accompanied by a significant fall in blood glucose levels. Nicotine had no effect. Carbachol was found to enhance insulin release in a dose-dependent manner. Muscarinic blockade by atropine or methylatropine totally suppressed carbachol-induced insulin secretion. No blocking effect was accomplished by beta-adrenoceptor blockade. Glucose-induced insulin secretion was not affected by atropine in normal non-fasted mice. In mice fasted for 24 h, however, the insulin response to glucose was impaired by atropine suggesting that the nutritional state is important for cholinergic modulation of glucose-induced insulin response. Pretreatment of animals with the glycogenolytic hydrolase, acid amyloglucosidase, enhanced tolbutamide-induced insulin release but did not influence insulin secretion stimulated by carbachol. Pretreatment with the monoamine oxidase inhibitor, pargyline, plus L-dopa, leading to an intracellular accumulation of dopamine in the insulin cells, totally suppressed carbachol-induced insulin release. It is suggested that, in mice, cholinergic stimulation promotes insulin secretion through activation of muscarinic receptors on the insulin cell. Blockade of these receptors does not influence glucose-stimulated insulin release in the non-fasting state, but may impair the insulin response to glucose after fasting. Cholinergic stimulation of insulin release is inhibited after L-dopa-induced accumulation of dopamine in the insulin cells. In contrast to tolbutamide-induced insulin release cholinergic insulin release is not dependent on acid amyloglucosidase activity.

Animals↗
PubMed1982

In vitro inhibition of pancreatic enzyme activities by dietary fiber.

Trypsin, amylase, lipase and phospholipase activities were assayed in buffer solutions and in human duodenal juice after incubation with different types of dietary fiber. In buffer solutions, trypsin activity was slightly reduced and amylase activity heavily reduced by pectin of low methylic esterification (LM pectin). Lipase activity was markedly reduced by LM pectin and also moderately reduced by pectin of high methylic esterification (HM pectin). Phospholipase was hardly influenced at all by fiber. Activities of pancreatic enzymes in human duodenal juice were examined after in vitro incubation with pectins, guar gum, wheat bran and ispaghula. Ispaghula did not affect the enzymes except for lipase activity, which was moderately inhibited. The other fiber preparations examined reduced amylase activity by 35-100% at fiber concentrations of up to 1.5 g%, lipase by 40-95% and trypsin by 40-85%. LM pectin had the strongest inhibitory effect among the different fiber preparations studied. Phospholipase activity was only influenced by the pectins, which caused a 75% reduction. It is concluded that dietary fiber of different kinds has the capacity to inhibit pancreatic enzyme activities. This inhibitory effect is dependent on the type of fiber and differently affects the different enzymes. Further, the inhibition seems to be more pronounced when exerted in human duodenal juice than in conventional buffer systems.

Buffers↗
PubMed1982

Influence of glucagon, gastric inhibitory polypeptide, pancreatic polypeptide and somatostatin on beta-adrenergically induced insulin secretion in the mouse.

The effect of four polypeptides, glucagon, Gastric Inhibitory Polypeptide (GIP), Pancreatic Polypeptide (PP) and somatostatin on beta-adrenoceptor stimulated insulin secretion in vivo in the mouse was investigated. The beta-adrenoceptor stimulation was induced by isoprenaline (IPNA). It was found that at dose levels without influence on basal insulin secretion the polypeptides produced the following pattern of interaction with IPNA. Insulin secretion induced by IPNA was increased by glucagon and inhibited by somatostatin. GIP and PP did not change IPNA-induced insulin release. It is concluded from this and earlier published studies that glucagon, but not always GIP, serves as a positive modulator of basal and stimulated insulin secretion, and that somatostatin is a general inhibitor of insulin release. beta-Adrenoceptor-induced insulin secretion however, seems to be less sensitive to somatostatin than insulin release induced by glucose.

Animals↗
PubMed1982

Effect of dietary fiber on pancreatic enzyme activity in vitro.

The importance of various factors for dietary fiber effects on pancreatic enzyme activities was studied in vitro. Pectin of high methylic esterification and guar gum, which reduced enzyme activities, particularly lipase activity, increased the viscosity of duodenal juice. Increasing duodenal juice viscosity by polyethlene glycol also caused a reduction particularly of lipase activity. Pectin of low methylic esterification, which reduced especially amylase and lipase activities, significantly lowered duodenal juice pH. Lowering duodenal juice pH by hydrochloric acid caused a reduction especially of amylase and lipase activities. Pretreating fiber at acid pH tended to increase its enzyme-inhibiting properties. Trypsin adsorption to wheat bran was partly reversible by buffer washings. Changing ionic strength and incubation time appeared relatively unimportant for the effects of the fiber on enzymes. It is assumed that the inhibitory effects of the fiber on enzymes are attributed inter alia to effects on viscosity, pH, and adsorption, and further that gastric acidification of fiber and conditions lowering intestinal pH may enhance these effects.

Adsorption↗
PubMed1982

Influence of gastrointestinal hormones on the course of acute experimental pancreatitis.

The influence of exogenous administration and endogenous release of certain g.i. hormones on the course of acute experimental pancreatitis was studied. Administration of 2 g of a pellet diet every eight hours decreased survival, as did repeated s.c. administration of the cholecystokinin-analogue caerulein. Also oral administration of a trypsin inhibitor--releasing intestinal factors or hormones stimulating pancreatic enzyme synthesis and secretion--decreased survival. On the other hand repeated s.c. administration of secretin or an anticholinergic drug (Pro-Banthine), or oral administration of 0.1 N HCl every eight hours did not influence survival. At blind macroscopic evaluation, caerulein was found to cause signs of more severe disease. All pancreatic rats had increased S-amylase levels, but there was no difference between any of the groups. In peritoneal fluid, however, caerulein caused an increase in the amylase activity. The results suggest that elevated S-levels of g.i. hormones, which primarily stimulate pancreatic enzyme synthesis and secretion, are harmful in acute experimental pancreatitis.

Acute Disease↗
PubMed1981

Effects of 4-aminopyridine on insulin secretion and plasma glucose levels in intact and adrenalectomized-chemically sympathectomized mice.

The effects of 4-aminopyridine (4-AP) on basal and glucose-induced insulin secretion and on plasma glucose concentrations were investigated in vivo in intact mice and in mice subjected to surgical adrenalectomy plus chemical sympathectomy induced by 6-hydroxydopamine. In normal intact mice, an i.v. injection of 4-AP, 26 micro mol/kg, induced an elevation of plasma glucose concentrations from 6.4 +/- 2 to 10.0 +/- 0.3 mmol/1 (P less than 0.001) seen after 30 min. Thereafter the plasma glucose concentration gradually returned to the normal level. Despite this marked elevation of plasma glucose levels, no change in plasma insulin concentrations was seen. In intact normal mice, the insulin secretion induced by a half-maximal dose of glucose was partially inhibited by 4-AP, 0.26 micro mol/kg. No further inhibition was observed after a larger dose, 26 micro mol/kg. In adrenalectomized-chemically sympathectomized mice, 4-AP, 26 micro mol/kg, did not affect plasma glucose concentrations or plasma levels of insulin. In these animals, 4-AP potentiated glucose-induced insulin secretion by approximately 65% at the two dose levels studied. This potentiation of glucose-induced insulin secretion was not affected by muscarinic receptor blockade. In summary, 4-AP increased plasma glucose levels in normal intact mice, but had no effect on plasma glucose levels in adrenalectomized-chemically sympathectomized mice. In addition, 4-AP inhibited glucose-induced insulin secretion in normal intact mice, but potentiated glucose-induced insulin secretion in adrenalectomized-chemically sympathectomized mice. It is concluded that the effect of 4-AP on insulin secretion and plasma glucose levels in normal mice is exerted indirectly, through stimulation of the sympatho-adrenal system. Further, from the results obtained in animals deprived of their sympatho-adrenal system it is suggested that the drug also has the capability to stimulate insulin secretion by acting directly on the insulin secreting cells.

4-Aminopyridine↗
PubMed1981

Effects of selective and non-selective beta-adrenergic agents on insulin secretion in vivo.

The effects of various beta-adrenergic agents on insulin secretion were investigated in vivo in mice. The non-selective beta-stimulator isopropylnoradrenaline and the selective beta 2-stimulator terbutaline both stimulated insulin secretion markedly, with the same efficacy and in a dose-dependent manner. The peak levels of plasma insulin after these two beta-agonists were achieved at a later time point (5-6 min) than after stimulation with glucose or carbachol (1.5-2.5 min). At very high dose levels the beta 2-stimulator isopropylaminothiazoloxypropanol slightly increased plasma insulin concentrations. The non-selective beta-blocker propranolol and the beta 2-selective blocker ICI 188,551 inhibited terbutaline-induced insulin release markedly and at comparable low dose levels, whereas the selective beta 1-blocker metoprolol exerted this effect only at a high dose level. At higher dose levels these three blockers moderately depressed the insulin response to glucose suggesting a partial dependence on intact beta-adrenoceptors for the effect of glucose. The beta 2-blocker butoxamine and the beta 1-blocker pamatolol did not influence insulin secretion. In conclusion, beta-adrenoceptor stimulation enhanced insulin secretion in vivo, but the beta-adrenoceptors regulating insulin secretion do not fit well into the conventional subdivision of beta 1 and beta 2, though they apparently are mainly of the beta 2-type.

Adrenergic beta-Agonists↗