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I Lundquist

Publications and source records attributed to I Lundquist.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of islet nitric oxide synthase increases arginine-induced insulin release.

NG-Nitro-L-arginine, an inhibitor of nitric oxide (NO) synthase, markedly (+50%) increased the L-arginine-induced insulin release from isolated mouse islets but did not itself influence insulin secretion. An abundance of mouse islet cells were positively stained for the enzyme NADPH diaphorase, which reportedly is a marker for NO synthase. The data suggest that the NO synthase activity in mouse islet tissue may inhibit insulin secreting processes and that L-arginine has a dual action on insulin release.

Amino Acid Oxidoreductases↗
PubMed1992

Homologous islet amyloid polypeptide: effects on plasma levels of glucagon, insulin and glucose in the mouse.

We examined the effects of a single intravenous injection of homologous islet amyloid polypeptide (IAPP) on the plasma levels of glucagon, insulin and glucose in the freely fed mouse. It was observed that IAPP suppressed basal glucagon levels concomitant with a decrease of the blood glucose concentrations. Basal plasma insulin levels were not affected. IAPP did not appreciably modulate the plasma concentration of glucose, insulin or glucagon after an intravenous glucose load. Further, IAPP inhibited the insulin secretory response to beta 2-adrenoceptor stimulation. IAPP also lowered the plasma glucagon levels following beta 2-adrenoceptor stimulation, whereas no apparent effect on plasma levels of glucose was observed. The data suggest that IAPP suppresses glucagon secretion and lowers blood glucose levels in the freely fed mouse. It might also exhibit a negative feedback inhibition on beta 2-adrenoceptor-induced insulin secretion, but has little influence on glucose-induced insulin release. Since IAPP is co-secreted with insulin, it is not inconceivable, that in the freely fed mouse, IAPP may act to amplify the blood glucose lowering effect of insulin through a direct suppression of glucagon secretion via the islet microcirculation.

Amyloid↗
PubMed1992

The relationship of islet amyloglucosidase activity and glucose-induced insulin secretion.

We have previously presented evidence for the involvement of islet acid amyloglucosidase, a lysosomal glycogen-hydrolyzing enzyme, in certain insulin secretory processes. In the present investigation, we studied whether differential changes in islet amyloglucosidase activity could be related to the insulin secretory response to glucose. It was observed that the dose-response curve for glucose-induced insulin response in vivo was shifted to the left by pretreatment of mice with purified fungal amyloglucosidase. In enzyme-pretreated mice, the ED50 was 2.1 mmol/kg glucose as compared with 5.7 mmol/kg in saline-pretreated controls (p less than 0.005). Also, the maximal insulin response to glucose was enhanced by amyloglucosidase pretreatment. Parenteral administration to mice (four injections during 2 days) of the pseudotetrasaccharide acarbose, a recognized inhibitor of intestinal alpha-glucosidases, surprisingly induced a marked increase in the activities of islet acid amyloglucosidase (+ 120%; p less than 0.001) and acid alpha-glucosidase (+ 45%; p less than 0.01) without affecting the activities of other lysosomal enzymes such as acid phosphatase and N-acetyl-beta-D-glucosaminidase. No effect on the microsomal neutral alpha-glucosidase was recorded. Moreover, in these mice, the insulin secretory response to glucose was enhanced both at a maximal dose of glucose 11.1 mmol/kg and at a dose in the ED25-ED50 range, 3.3 mmol/kg (p less than 0.005). Direct addition of acarbose to islet homogenates strongly suppressed acid amyloglucosidase activity, the EC50 being approximately 1 microM. Acid alpha-glucosidase activity was also strongly inhibited, whereas the activities of acid phosphatase and N-acetyl-beta-D-glucosaminidase were unaffected. Neutral alpha-glucosidase was slightly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acarbose↗
PubMed1991

Effect of L-dopa administration on islet monoamine oxidase activity and glucose-induced insulin release in the mouse.

Previous studies have shown that the amine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is rapidly converted to its corresponding amine, dopamine, in islet beta-cells. In the present investigation, we studied the effect of acute L-DOPA administration on islet monoamine oxidase (MAO) activity and on glucose-induced insulin secretory response in mice. It was observed that at 2 min after intravenous L-DOPA administration, there was a marked increase (+35%) in islet MAO activity, with serotonin as substrate. At 7 min, MAO activity towards dopamine was enhanced by 32% and that towards serotonin and phenylethylamine (PEA) was decreased by 23 and 25%, respectively. The inhibitor of L-aromatic amino acid decarboxylase, benserazide, abolished L-DOPA-induced changes of MAO activity, suggesting that the formed dopamine, and not L-DOPA itself, was responsible for the observed effects. At 60 min, no effect by L-DOPA administration on islet MAO activity was noticed. L-DOPA (125 or 250 mumol/kg), given together with glucose, induced a decrease in glucose-induced insulin response. L-DOPA (125 mumol/kg), given 7 min before glucose, totally suppressed glucose-induced insulin response. This inhibition was eliminated through pretreatment with benserazide. Enhancement of glucose-stimulated insulin response, after deposition of horseradish peroxidase (HRP) in beta-cell vacuolar system, was suppressed by L-DOPA. We conclude that acute L-DOPA-induced dopamine accumulation in pancreatic islets is accompanied by rapid changes in MAO activity, concomitant with an inhibitory effect on glucose-stimulated insulin response. Increased hydrogen peroxide production, following increased MAO activity, may possibly augment the inhibitory effect of dopamine accumulation on insulin release.

Animals↗
PubMed1991

Effect of the lysosomotropic drug suramin on islet lysosomal enzyme activities and the insulin-secretory response induced by various secretagogues.

The trypanocidal drug suramin is known to concentrate in lysosomes and to depress the activity of different lysosomal enzymes. We have previously shown that suramin can inhibit the activity of the islet lysosomal enzyme acid amyloglucosidase, a glycogenolytic glucose-producing hydrolase, which seems to be involved in certain insulin-secretory processes. In the present investigation we studied the pH dependency and dose-response effects of suramin on islet lysosomal enzyme activities as well as the effect of suramin treatment on the insulin-secretory response to various secretagogues in mice. It was found that two injections of suramin (0.18 mmol/kg) to normal NMRI mice at -24 and -2 h induced a moderate depression of the activities of islet acid amyloglucosidase (-22%) and acid phosphatase (-13%), whereas no effect was recorded for the activities of acid alpha-glucosidase, N-acetyl-beta-D-glucosaminidase and the non-lysosomal enzyme neutral alpha-glucosidase. Direct addition of different concentrations of suramin to islet homogenates showed that the drug was a potent inhibitor of acid amyloglucosidase and acid alpha-glucosidase at pH 4.0. At pH 5.0, suramin induced a large increase in acid alpha-glucosidase activity, whereas acid amyloglucosidase and acid phosphatase were inhibited. Suramin-injected mice showed a reduced insulin-secretory response to the sulphonylurea drug glibenclamide (-45%), whereas the insulin response to the cholinergic agonist carbachol or the phosphodiesterase inhibitor IBMX (1-isobutyl-3-methylxanthine) was unaffected. It is concluded that suramin inhibits islet acid amyloglucosidase activity in vivo and in vitro, whereas its effect on acid alpha-glucosidase is complex and pH dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1991

Cholecystokinin is not a major determinant for the changes in beta-cell function seen after pancreatico-biliary diversion in rats.

The influence of longterm increase in the plasma CCK levels on beta-cell function in rats was studied by using the pancreatico-biliary diversion (PBD) model. An intravenous glucose load (800 mg glucose/kg) was performed three weeks after the PBD operation. Additionally a group of PBD operated animals as well as an unoperated group received the CCK receptor antagonist L364,718 continuously during the three week study period. The proliferation rate of endocrine pancreatic cells was studied by means of 3H-thymidine administration. PBD caused a decrease in basal levels of insulin and glucose and an augmented insulin secretory response after glucose injection. There was no appreciable influence on the glucose elimination rate. When PBD animals were given the CCK receptor antagonist no differences were observed with regard to insulin and glucose compared to PBD animals without antagonist. The CCK-antagonist did not influence the beta-cell function in unoperated animals. Further, the proliferation rate of the endocrine pancreatic cells was not significantly changed in the PBD rats. The results suggest that PBD is accompanied by significant changes in basal and stimulated insulin secretion. These changes are probably not a direct consequence of the increased plasma CCK levels that follows PBD. Moreover, the insulin secretory response to glucose in normal rats was not influenced by longterm administration of the CCK receptor antagonist. Our observations should encourage further studies on the complex entero-insular interactions following pancreaticobiliary diversion.

Animals↗
PubMed1986

Insulin secretion and lysosomal enzyme activities in isolated mouse islets. Effects of glucose, diazoxide and isobutylmethylxanthine.

The influences of glucose, the benzothiadiazide derivative diazoxide (an inhibitor of insulin release), and the potent non-glucose insulin secretagogue 3-isobutyl-1-methylxanthine (IBMX) on insulin secretion and the activities of 3 different lysosomal enzymes were studied in isolated mouse islets. We found that the increase in insulin secretion during a 4 hr incubation period in the presence of 16.7 mM glucose was accompanied by an increase in islet activities of the lysosomal enzymes acid amyloglucosidase and acid alpha-glucosidase. These alpha-1,4-glucoside splitting enzyme activities were increased by 45-55% (p less than 0.01). No influence by glucose was encountered for the activities of N-acetyl-beta-D-glucosaminidase or the non-lysosomal neutral alpha-glucosidase. Upon incubation with 0.2 mM diazoxide and glucose (16.7 mM) the glucose-induced insulin secretion was markedly suppressed and no significant increase in islet lysosomal enzyme activities was observed. On the other hand, insulin secretion induced by IBMX to the same magnitude as with 16.7 mM glucose, was accompanied by an increase in islet activity of N-acetyl-beta-D-glucosaminidase (p less than 0.05), whereas no apparent changes in acid amyloglucosidase and acid alpha-glucosidase activities could be detected. In conclusion, the determination of lysosomal enzyme activities in isolated mouse islets revealed that glucose was able to induce an increased activity of glucose producing glycogenolytic acid hydrolases under conditions when a concomitant insulin secretion occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1985

Glucose tolerance and insulin and C-peptide responses after various insulin secretory stimuli in hyper- and hypothyroid subjects before and after treatment.

Immunoreactive insulin (IRI) and C-peptide secretory responses to terbutaline, glucagon, glucose and a standardized meal during continuous blood glucose monitoring were investigated in hyper- and hypothyroid patients before and after treatment. The beta 2-adrenoceptor agonist terbutaline (125 micrograms IV) induced prompt IRI and C-peptide responses in hyperthyroid patients. On the contrary, in the hypothyroid, no insulin or C-peptide responses were seen despite a slight enhancement of blood glucose concentrations. Thyroxine treatment of these patients improved the IRI and C-peptide responses and no blood glucose increment was then seen. Glucagon (250 micrograms IV) induced prominent IRI and C-peptide responses of similar magnitude in hyper- and hypothyroid patients before as well as after treatment. Before treatment, the blood glucose increment was greater in the hypothyroid patients than in the hyperthyroid but after treatment no difference between the 2 groups was seen. After a small load of glucose (6 g IV) no apparent difference in glucose tolerance was seen between hyper- and hypothyroid patients. However, the hyperthyroid patients had greater IRI and C-peptide responses to glucose than the hypothyroid but the differences diminished after treatment. Before treatment, hypothyroid patients had lower blood glucose response to a meal intake than hyperthyroid patients but no differences were seen between the 2 patient groups with regard to IRI- and C-peptide responses. After treatment, no differences between the 2 groups were seen with regard to blood glucose, IRI or C-peptide responses to the meal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1979

Insulin secretion and carbohydrate metabolism in the dystrophic mouse.

Dystrophic mice were investigated with regard to their regulation of blood glucose and insulin secretion in vivo. The following were also measured: tissue glycogen levels, activity of the glycogenolytic hydrolase, acid amyloglucosidase, and in vitro glucose utilization by liver, muscle and adipose tissue. Basal levels of blood glucose and plasma insulin of dystrophic mice were essentially within the same range as in the clinically unaffected littermate controls. Dystrophic mice had a decreased tolerance to glucose and glibenclamide; the secretion of insulin in response to these secretagogues was moderately reduced. Insulin release following beta-adrenergic stimulation, however, was increased in the dystrophic mice. Glycogen levels and acid amyloglucosidase activity were increased in dystrophic muscles but were normal in liver. Acid amyloglucosidase activity in pancreatic islets was lower in the dystrophic mouse. Glucose utilization in vitro appeared normal in liver tissue from dystrophic mice; in dystrophic muscle there was a threefold increase in 14CO2-production with no concomitant increase in either glycogen or 14C-incorporation into glycogen. 14CO2 production and 14C-incorporation into lipid and glycogen were increased in dystrophic adipose tissue. We suggest that the decreased glucose tolerance, and the reduced insulin response to glucose in the dystrophic mouse are compensated by an increased glucose utilization in muscle and adipose tissue and an increased beta-adrenergic-mediated secretion of insulin.

Adipose Tissue↗
PubMed1979

T-tubule endocytosis in dystrophic chicken muscle and its relation to muscle fiber degeneration.

Pectoralis muscles from normal and dystrophic chickens were investigated 2 h after an i.v. injection of horseradish peroxidase, by cytochemical and biochemical techniques to demonstrate peroxidase activity. Light microscopic examination of dystrophic muscles showed that peroxidase activity could be detected inside a population of fibers, in deliminated bodies often restricted to segments of the muscle fiber. Such bodies containing peroxidase were not observed in normal muscle fibers. Electron microscopy of dystrophic muscle fibers revealed that numerous vesicles containing peroxidase were frequently present in fiber regions with signs of cytoplasmic degradation. These vesicles, which occasionally were found to be coated, were 50--100 nm in size and appeared to be derived from t-tubules. Larger (up to 1.7 micrometers) inclusions containing peroxidase and delimited by a single membrane were also present at degenerating areas of dystrophic muscle fibers. These bodies seemed to be formed by fusion between several primary t-tubule vesicles and probably also lysosomes. Vacuoles containing the peroxidase were frequently encountered. Biochemical determination of horseradish peroxidase activity, performed after extensive washing of the muscle tissue, showed that dystrophic muscles contained about twice as much peroxidase as normal control muscles. It is suggested that endocytosis from t-tubules is an early and essential pathological phenomenon in dystrophic muscle fibers, which may be related to lysosomal function and muscle fiber degeneration

Animals↗
PubMed1979

Inhibitory effect of somatostatin on insulin secretion during alpha-adrenergic blockade in three different species.

It has recently been suggested from experiments in dogs that somatostatin suppresses insulin release via a stimulation of the inhibitory alpha-adrenoceptors of the pancreatic B-cell. The effect of somatostatin on insulin secretion during alpha-adrenergic blockade with phentolamine was therefore studied in three different species; the rat, the cat and the mouse. It was found that somatostatin significantly depressed insulin release during alpha-adrenoceptor blockade in all three species. In the rat, infusion of somatostatin at a dose of 0.3 microgram/kg/min decreased basal plasma insulin concentration by 92%. In the presence of phentolamine, the same dose of somatostatin lowered plasma insulin by 85%. In the cat, a similar infusion of somatostatin lowered basal plasma insulin concentration by 87%, but its depressive effect during alpha-adrenergic blockade was comparatively less pronounced (68%) than in the rat. In the mouse, a single iv injection of somatostatin induced a short-lasting depression of plasma insulin concentration during alpha-adrenergic blockade. From these results it seems unlikely that somatostatin should inhibit insulin release simply by stimulation of alpha-adrenoceptors on the B-cell. It cannot be ruled out, however, that a more complex interaction exists between somatostatin and the sympatho-adrenal system with regard to the control of insulin secretion.

Animals↗
PubMed1979

Influence of anticholinergic treatment on rat pancreatic protein and amylase concentrations.

Pancreatic protein and amylase concentrations were measured after subcutaneous administration of an anticholinergic drug (Pro-Banthine to rats in different doses. In doses comparable to those given in acute pancreatitis an increase of both pancreatic protein and amylase concentrations was found. If pancreatitis is indeed caused or maintained by proteases released from the acinar cell, anticholinergics--giving rise to an accumulation of enzymes within the pancreas--may do more harm than good in the treatment of acute pancreatitis.

Acute Disease↗
PubMed1979

Trypsin as a regulator of pancreatic secretion in the rat.

The effect of intraduodenally administered trypsin on pancreatic exocrine secretion was investigated in conscious rats surgically prepared with bile--pancreatic fistulae. Introduction of NaHCO3 into the duodenum did not influence pancreatic secretion. Reintroduction of bile--pancreatic juice into the duodenum, however, suppressed pancreatic protein output, mainly because of changes in protein concentration. Infusion of trypsin into the duodenum in the absence of intraluminal pancreatic juice significantly suppressed the secretory volume and pancreatic enzyme output; addition of trypsin inhibitor to the trypsin infusion resulted in an immediate increase of pancreatic secretion. Trypsin inhibitor per se, however, was without effect. Bile--pancreatic juice affected amylase, kipase, and trypsinogen output in a parallel fashion; after addition of trypsin inhibitor to the infusion the inhibitory effects on pancreatic enzyme output was reversed in a parallel manner. The results support the hypothesis that pancreatic exocrine secretion is regulated by a feedback mechanism exerted--at least partly--by intraluminal trypsin.

Amylases↗
PubMed1978

beta-Adrenergic insulin release and adrenergic innervation of mouse pancreatic islets.

An investigation of the stereospecificity of beta-adrenergic insulin release, its relation to alpha-adrenergic blockade and the adrenergic innervation of the pancreatic islets was performed in the mouse. It was observed that in vivo beta-adrenergic stimulation of insulin release by isopropylnoradrenaline was stereospecific for the L-stereoisomer and selectively blocked by the L-isomer of the beta-adrenergic antagonist L-propranolol. D-propranolol had no effect. Pretreatment of mice with a dose of D-isopropylnoradrenaline devoid of insulin releasing activity, slightly increased the subsequent insulin response to a half-maximal dose of L-isopropylnoradrenaline. Basal insulin secretion was blocked by L-propranolol (beta-adrenergic blockade) and increased by phentolamine (alpha-adrenergic blockade). A beta-blocked insulin response to L-isopropyl-noradrenaline could be overcome by alpha-adrenergic blockade depending on the dose of the beta-agonist, suggesting a close association between the adrenergic receptors. The adrenergic innervation of the islet cells was studied by electron microscopic autoradiography after injection of 3H-L-noradrenaline. It was observed that labelled adrenergic nerve terminals were associated with both A1- (D-), A2- and B-cells. The nerves were mainly distributed in the periphery of the islets either as single axons or as bundles. The majority of the terminals were associated with A2-cells, the most frequent cell type in the islet periphery. However, in all islets examined terminals were found close to B-cells. Adrenergic terminals often caused indentations in the contour of an islet cell and were separated from the islet cell membrane only by a narrow intercellular space, about 20 nm in width. It is concluded that the islet cells of the mouse are equipped with the morphological substrate for direct adrenergic regulation. Further it is suggested that the B-cell is supplied with L-stereospecific beta-adrenergic receptors and that the alpha- and beta-adrenergic receptors are at least partially interrelated.

Adrenergic Fibers↗
PubMed1978

Lysosomal activation in mouse skeletal muscle induced by protamine in vitro.

Incubation of mouse skeletal muscle in a physiological Ringer solution containing protamine (60 microgram/ml) at +37 degrees C for 1 h induced ultrastructural changes including proliferation of tubular profiles and vesicles at the I-band level close to the A-I junction, formation of numerous acid phosphatase positive lysosomes in the longitudinal sarcoplasmic reticulum and autophagic vacuolation starting at the level of the A-I junction. Biochemical determination of acid phosphatase in the incubated muscles showed that protamine caused an increase in acid phosphatase activity of about 25% compared to enzyme activities obtained from muscles incubated without protamine at +37 degrees C or with protamine at +4 degrees C. The morphological findings suggest that the vesicles arising adjacent to the A-I junction originate from transverse tubules. Such vesicles, designated as endocytic, may acquire acid phosphatase activity in the longitudinal SR ano be active in an autophagic process resulting in large vacuoles. A causal relationship between endocytosis and lysosomal activation is suggested.

Acid Phosphatase↗