Biomedical subjects

I Lundquist

Publications and source records attributed to I Lundquist.

At least 73 records · Page 4Linked to original sources

PubMed1988

Selective alpha 2-adrenoceptor activation by clonidine: effects on 45Ca2+ efflux and insulin secretion from isolated rat islets.

A possible role for Ca2+ in the alpha-adrenoceptor-induced inhibition of glucose-stimulated insulin secretion was studied in isolated rat islets by the use of the selective alpha 2-adrenoceptor agonist clonidine. We found that clonidine, in contrast to the alpha 1-adrenoceptor agonist phenylephrine, inhibited glucose-stimulated insulin secretion at dose levels below 10(-6) mol l-1. In islets preloaded with 45Ca2+ and perifused at 2 mmol l-1 Ca2+, clonidine (10(-6) mol l-1) reduced the glucose (13.3 mmol l-1)-stimulated 45Ca2+ efflux during both the first and second phases of insulin secretion. Furthermore, the inhibitory effect of clonidine on glucose (13.3 mmol l-1)-stimulated insulin secretion was partially counteracted by raising the extracellular Ca2+ concentrations. Moreover, the calcium channel agonist Bay K 8644 counteracted the inhibition by clonidine on glucose-stimulated insulin secretion. Our results suggest that selective alpha 2-adrenoceptor-induced inhibition of glucose-stimulated insulin secretion is mediated, at least partially, by restraint of Ca2+-influx. This action might in turn be exerted through interference with the voltage-dependent calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1988

Islet hormone secretion and islet lysosomal enzyme activities in the mouse: effects of chloroquine.

To examine the function of islet lysosomal enzymes in islet hormone secretory mechanisms, we investigated the effects of the lysosomotropic drug chloroquine on islet lysosomal enzyme activities and basal as well as stimulated insulin and glucagon secretion. Chloroquine, added to islet homogenates, did not affect the activities of the lysosomal enzymes acid amyloglucosidase, acid alpha-glucosidase, or N-acetyl-beta-D-glucosaminidase. The activity of acid phosphatase, however, was inhibited at a high concentration of chloroquine (10(-3) M). When injected together with glucose, chloroquine (2 or 10 mumol/kg) inhibited the peak plasma insulin response. Similarly, at 24 hrs after chloroquine injection (100 mumol/kg), the plasma insulin response to glucose was reduced. In contrast, islets isolated from mice pretreated 24 hrs before with chloroquine, displayed glucose-stimulated insulin secretion in vitro that was not different from controls. Such islets showed, furthermore, enhanced activities of the enzymes acid phosphatase and neutral alpha-glucosidase but not of acid amyloglucosidase, acid alpha-glucosidase or N-acetyl-beta-D-glucosaminidase. Arginine-stimulated insulin response in vivo displayed a complex pattern; it was increased when arginine was injected together with chloroquine but decreased at 24 hrs after chloroquine administration. Arginine-stimulated glucagon secretion was not affected by chloroquine. We conclude that chloroquine pretreatment 24 hrs prior to glucose injection decreases glucose-stimulated insulin secretion in vivo by mechanisms that are not correlated to an inhibitory action on islet activities of glycogenolytic lysosomal enzymes.

Animals↗

PubMed1987

Alpha 1- and alpha 2-adrenoceptor activation increases plasma glucagon levels in the mouse.

The effects of activation of the alpha-adrenoceptors on glucagon secretion are not yet clear. We therefore injected the alpha 1-selective agonist phenylephrine and the alpha 2-selective agonist clonidine (0.05-50 nmol/kg) intravenously to mice and measured the plasma glucagon levels. We found that both phenylephrine and clonidine enhanced the plasma glucagon levels. The peak level of plasma glucagon was seen at 2 min after clonidine injection whereas phenylephrine enhanced the plasma glucagon levels throughout a 10 min period after the injection. Furthermore, both clonidine and phenylephrine potentiated the plasma glucagon response to the cholinergic agonist carbachol and exerted additive stimulatory effects on the plasma glucagon response to both the beta-adrenoceptor agonist terbutaline and the C-terminal octapeptide of cholecystokinin, CCK-8. The elevated plasma insulin levels after injection of carbachol or terbutaline were lowered by clonidine but not by phenylephrine whereas the CCK-8-induced increase in plasma insulin levels was not affected by either clonidine or phenylephrine. We conclude that both alpha 1- and alpha 2-adrenoceptor activation enhances plasma glucagon levels in the mouse, and that alpha 2- but not alpha 1-adrenoceptor activation lowers plasma insulin levels.

Adrenergic alpha-Agonists↗

PubMed1987

Neuropeptide Y: intrapancreatic neuronal localization and effects on insulin secretion in the mouse.

The intrapancreatic localization and the effects on basal and stimulated insulin secretion of neuropeptide Y (NPY) were investigated in the mouse. Immunocytochemistry showed NPY to be confined to intrapancreatic nerve fibers mainly associated with blood vessels. Fine varicose NPY fibers were also detected in the exocrine parenchyma and occasionally also within the islets. Double-staining experiments with the use of antisera for both NPY and tyrosine hydroxylase (TH) indicated that most of the NPY fibers were nonadrenergic in nature. Only a population of the NPY fibers occurring around blood vessels showed TH immunoreactivity. Under in vivo conditions, NPY was found to elevate plasma insulin levels slightly when injected intravenously at the high dose level of 8.5 nmol/kg. At lower dose levels, NPY did not affect basal plasma insulin levels, but instead inhibited glucose-induced insulin secretion. Thus, the glucose-induced increment in plasma insulin levels, which was 120 +/- 7 microU/ml in controls, was reduced to 87 +/- 5 microU/ml by NPY at 4.25 nmol/kg (p less than 0.01) and to 98 +/- 6 microU/ml by NPY at 1.06 nmol/kg (p less than 0.05). In contrast, the insulin secretory response to the cholinergic agonist carbachol was not affected by NPY. We conclude that NPY nerve fibers occur in the mouse pancreas and that most of these NPY nerve fibers are nonadrenergic. Furthermore, in the mouse, NPY enhances basal plasma insulin levels at high dose levels and inhibits glucose-induced, but not cholinergically induced insulin secretion at lower dose levels under in vivo conditions.

Animals↗

PubMed1987

Alpha-adrenoceptor blockade by phentolamine inhibits beta-adrenergically and cholinergically induced glucagon secretion in the mouse.

Glucagon secretion is known to be stimulated by activation of the alpha-adrenoceptors. In this study, we investigated whether alpha-adrenoceptor blockade by phentolamine affects basal and stimulated glucagon secretion in the mouse. Phentolamine was injected intraperitoneally to mice at dose levels varying from 2.6 to 260 mumol/kg. It was found that, while decreasing plasma glucose levels, phentolamine did not over this wide dose range affect basal glucagon concentrations indicating an inhibition of the hypoglycaemia-induced glucagon secretion. Further, phentolamine clearly inhibited the glucagon secretory response to beta-adrenergic or cholinergic stimulation. Thus, phentolamine (2.6 mumol/kg), impaired the glucagon secretory response to the beta 2-adrenoceptor agonist terbutaline by 51% (P less than 0.01), and to the cholinergic agonist carbachol by 44% (P less than 0.02). We conclude that alpha-adrenoceptor blockade by phentolamine inhibits the glucagon secretion following hypoglycaemia or stimulation by beta-adrenergic and cholinergic agonists. Thus, the alpha-adrenoceptors seem to be of great importance for glucagon secretion in the mouse.

Adrenergic alpha-Antagonists↗

PubMed1987

Glycogen and glycogen-hydrolysing lysosomal enzyme activity in mouse liver: effects of fasting, adrenoceptor antagonism and insulin-induced hypoglycaemia.

Whereas the phosphorolytic breakdown of liver glycogen is known to be of great physiological importance, the functional role of the hydrolytic glycogenolysis in the lysosomal system is less well understood. In the present study the effects of fasting, alpha- and beta-adrenoceptor antagonism and insulin-induced hypoglycaemia on liver lysosomal glycogen-hydrolysing enzyme activity were investigated in mice. In freely fed mice the glycogen-hydrolysing activity (acid amyloglucosidase) was only 50% of the maltose-hydrolysing activity (acid maltase). Starvation for 24 h reduced the acid amyloglucosidase activity by approximately 30% (P less than 0.001), whereas the activities of acid maltase, acid phosphatase and beta-glucuronidase appeared unaffected. N-acetyl-beta-D-glucosaminidase activity was moderately (20%; P less than 0.01) enhanced by fasting. Thus, liver lysosomal enzyme activities may change independently of each other during fasting. Further, during short-term hypoglycaemic conditions (45 min) induced by endogenous or exogenous insulin, the activity of liver acid amyloglucosidase was found to be moderately reduced (15-20%). Blockade of alpha- and beta-adrenoceptors by phentolamine and propranolol did not result in any apparent influence on acid amyloglucosidase activity except for the indirect effect exerted by the phentolamine-induced hypoglycaemia. A moderate negative correlation (r = -0.51; P less than 0.001) between total liver glycogen concentration and acid amyloglucosidase activity was observed in a series of 43 freely fed NMRI mice. Our data show that in mouse liver the acid maltase activity predominates over the acid amyloglucosidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1987

Neuropeptide Y and calcitonin gene-related peptide: effects on glucagon and insulin secretion in the mouse.

Neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) are both intrapancreatic neuropeptides that are known to inhibit stimulated insulin secretion. In the present study, we examined their influences on basal and stimulated glucagon and insulin secretion in the mouse. Either NPY or CGRP was injected intravenously at two dose levels (0.85 or 4.25 nmol/kg). When injected alone, neither of them did affect basal plasma glucagon levels but CGRP reduced basal plasma insulin levels. Glucagon secretion stimulated by the cholinergic agonist carbachol was modestly inhibited by NPY at 4.25 nmol/kg (P less than 0.01) but not affected by CGRP. In contrast, glucagon secretion stimulated by the beta 2-adrenoceptor agonist terbutaline was markedly inhibited by NPY already at the lower dose level (P less than 0.01) and potentiated by CGRP (P less than 0.01). Insulin secretion stimulated by carbachol was inhibited by CGRP (P less than 0.01) but not affected by NPY, whereas terbutaline-induced insulin secretion was inhibited by both NPY (P less than 0.05) and CGRP (P less than 0.01). We conclude that the two intrapancreatic neuropeptides NPY and CGRP have opposite actions on stimulated glucagon secretion in the mouse: NPY in an inhibitory and CGRP in a potentiatory direction. Both peptides, however, inhibit insulin secretion stimulated by terbutaline.

Animals↗

PubMed1987

Biochemical determination of islet lysosomal enzyme activities following crinophagy-stimulating treatment with diazoxide in mice.

The pattern of islet lysosomal enzyme activities, islet insulin concentration and the plasma levels of insulin and glucose were studied in freely fed mice after the in vivo administration of diazoxide in doses known to induce crinophagy in islet beta-cells. After diazoxide treatment at time 0 and at 18 hr, the plasma glucose levels at 20 hr were markedly enhanced from 6.6 +/- 0.2 mmol/l (controls) to 27.2 +/- 2.7 mmol/l (diazoxide). Inhibition of insulin secretion by diazoxide was reflected in the insulinogenic index, which was reduced by approximately 40% (p less than 0.01) in the diazoxide-treated animals, who also displayed an increased concentration of islet insulin (+50%; p less than 0.01). Moreover, we found that the activities of certain lysosomal enzymes in islet tissue were markedly increased following diazoxide treatment. Thus the activities of the acid phosphatase, (+57%; p less than 0.02) the hexosaminidase N-acetyl-beta-D-glucosaminidase, (+52%; p less than 0.001), and the carboxyl proteinase cathepsin D (+41%; p less than 0.001), were all enhanced after diazoxide, whereas the activity of another lysosomal enzyme, the glycogen hydrolysing acid amyloglucosidase, was not altered by diazoxide treatment. The present data thus indicate that the morphological observation of diazoxide-induced crinophagy in pancreatic beta-cells has a biochemical correlate in enhanced levels of certain islet lysosomal enzyme activities known to participate in degradative processes. The results also suggest that islet lysosomal enzyme activities and/or lysosome populations can be modulated by a relative independence from each other.

Acetylglucosaminidase↗

PubMed1986

Effects of alpha 1- and alpha 2-adrenoceptor stimulation and blockade on plasma insulin levels in the mouse.

Stimulation of alpha-adrenoceptors is known to inhibit insulin secretion under a variety of conditions. In this study, the question of whether these alpha-adrenoceptors are of the alpha 1- or the alpha 2-subtype was investigated in the mouse. The selective alpha 2-adrenoceptor agonist clonidine (0.05-50 nmol/kg) was found to markedly inhibit the insulin secretory response to both glucose and the cholinergic agonist carbachol. This inhibition of insulin secretion was counteracted by the alpha 2-adrenoceptor antagonist yohimbine (2.6 mumol/kg), but not by the alpha 1-adrenoceptor antagonist prazosin (2.6 mumol/kg). In contrast, the alpha 1-adrenoceptor agonist phenylephrine (0.05-50 nmol/kg) did not affect the insulin secretory response to either glucose or carbachol. Moreover, both yohimbine and prazosin increased basal plasma insulin levels. It is concluded that alpha 1- and alpha 2-adrenoceptor blockade is followed by enhancement of basal plasma insulin levels in the mouse, whereas alpha 2-adrenoceptor stimulation but not alpha 1-adrenoceptor stimulation impairs the insulin secretory response to glucose and carbachol.

Adrenergic alpha-Agonists↗

PubMed1986

Effects of six cholecystokinin (CCK) fragments on insulin secretion in the mouse.

In a recent study it was demonstrated that the C-terminal octapeptide of cholecystokinin (CCK-26-33; often abbreviated CCK-8) and CCK-39 (= CCK--6-33) potently and with the same efficacy stimulated basal insulin secretion when injected intravenously to mice. In the present study, the effects of four other CCK fragments, CCK-30-33 (= CCK-4), CCK-1-33 (= CCK-33), CCK-1-21 (= CCK-21) and CCK-10-20, on basal and glucose-induced insulin secretion were studied. It was found that CCK-33 stimulated insulin secretion. At a dose level of 4.25 nmol/kg, plasma insulin concentrations were elevated by 58 +/- 7 microU/ml (P less than 0.001). On the contrary, neither CCK-4, nor CCK-21, nor CCK-10-20 displayed any effect on basal insulin secretion, not even at high dose levels. When injecting CCK-8, CCK-33 or CCK-39 at dose levels substimulatory on basal insulin secretion (0.53 nmol/kg), together with glucose, CCK-39 potentiated glucose-induced insulin secretion whereas CCK-8 and CCK-33 were without effects. In contrast, at the higher dose level of 5.3 nmol/kg, CCK-8, CCK-33, and CCK-39 all potentiated glucose-induced insulin secretion. The three other fragments, CCK-4, CCK-21, and CCK-10-20, were all without effects on glucose-induced insulin secretion. In conclusion, the potent stimulatory action on basal insulin secretion in the mouse exerted by various CCK fragments is confined to the C-terminal octapeptide (= CCK-8 or CCK-26-33).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Secretin potentiates cholinergically induced glucagon secretion in the mouse.

Glucagon secretion is stimulated by cholinergic activation, and it is known that the polypeptides VIP (vasoactive intestinal polypeptide) and GIP (gastric inhibitory polypeptide) both potentiate this cholinergically induced glucagon secretion. In this study, we investigated whether secretin, which shows structural similarities to both VIP and GIP, affects basal and cholinergically induced glucagon secretion in the mouse. Secretin was injected i.v. to mice at dose levels varying from 0.53 to 17 nmol kg-1, and plasma samples were taken at 2, 6 and 10 min following injection. It was found that secretin in this wide dose range did not affect basal glucagon concentrations. When the cholinergic agonist carbachol was injected i.v. at 0.16 mumol kg-1, plasma glucagon levels were elevated; at 2 min at 0.84 +/- 0.04 ng ml-1 compared to 0.31 +/- 0.02 ng ml-1 in controls (P less than 0.001). A combination of carbachol and secretin (4.25 nmol kg-1) enhanced plasma glucagon levels to 1.22 +/- 0.07 ng ml-1. Thus, secretin potentiated carbachol-induced glucagon secretion by 70% (P less than 0.001). Concomitantly, plasma glucose levels were elevated: 10.8 +/- 0.4 mmol l-1, compared to 9.2 +/- 0.4 mmol l-1 in controls (P less than 0.001). We conclude that secretin, while being without effect on basal glucagon secretion, markedly potentiates cholinergically induced glucagon secretion in the mouse, resulting in increased plasma glucose levels.

Animals↗

PubMed1986

Influence of bile duct occlusion on plasma insulin responses to glucose in rats.

The plasma insulin and glucose responses to intravenous glucose administration were studied in rats after 1, 3, and 6 weeks of bile duct occlusion. One week after the occlusion the first-phase plasma insulin response to glucose was clearly reduced, whereas the late-phase response was increased. Despite a relative hypoglycemia, a clearly increased glucose-induced elevation of plasma insulin was noted after 3 weeks' bile flow obstruction, at which time the median 15-min plasma insulin response to glucose was 38 microU/ml in duct-occluded rats and 7 microU/ml in control rats (p less than 0.001). At the same time an increased glucose elimination rate of 3.59%/min in duct-occluded rats and 3.08%/min in control rats (median values; p less than 0.05) was observed. Available evidence suggests that the effect on the insulin response may be induced by the trypsin-sensitive branch of the 'enteroinsular axis'.

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↗

PubMed1986

Differential changes in islet lysosomal enzyme activities in aging obese hyperglycemic mice.

The pattern of pancreatic islet lysosomal enzyme activities was investigated in adult obese mice (aged 5-7 months), old obese mice (aged 9-17 months) and aged-matched old "obese" mice suffering from excessive weight loss. A series of lean NMRI mice of comparable age was included as controls. It was observed that the islet activity of the glucose producing glycogenolytic hydrolase, acid amyloglucosidase, was excessively high in the adult obese mouse, being about 10 times higher than in the adult lean mouse. This high activity was reduced by about 65% in the islets of old obese mice and by about 80% in old mice suffering from weight loss. When glycogen and maltose were compared as substrates for the alpha-1,4-glucoside splitting activity, the ratio, glycogen splitting/maltose splitting activity in adult obese mice (1.68) showed amyloglucosidase predominance, whereas the ratio in old obese mice (0.67), and in old mice suffering from weight loss (0.79) revealed a significant change in this relation. The extremely elevated plasma insulin levels in the adult obese mice were reduced by about 65% in old obese mice and by about 95% in old mice with excessive weight loss and thus displaying the same pattern as islet amyloglucosidase activity. Further, in normoglycemic obese mice a highly significant correlation (r = 0.85; p less than 0.001) was found between islet acid amyloglucosidase activity and the actual insulin secretory rate as reflected by the plasma insulin concentrations. The activity of islet N-acetyl-beta-D-glucosaminidase showed an activity pattern opposite to that of acid amyloglucosidase.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

PubMed1986

Islet amyloglucosidase activity: some characteristics, and its relation to insulin secretion stimulated by various secretagogues.

The glucose-producing amylolytic activity in pancreatic islet tissue was characterized with regard to its properties with glycogen (amyloglucosidase) and maltose (maltase) as substrate, its optimum activity in islets from different strains of mice (NMRI, CBA and C-57BL) and after fasting, and its relation to the insulin secretory response after different secretagogues in vivo. Additionally the effects and fate of injected fungal acid amyloglucosidase were assessed. In the pancreatic islets of NMRI mice both the glycogen-splitting activity and the maltose-splitting activity displayed latency and an acid pH-optimum of about 5.0. After differential centrifugation a significant part of amyloglucosidase activity was found to be confined to the mitochondrial-lysosomal fraction. In crude islet homogenate the apparent Km for maltose at pH 5.0 was 2.1 mM. No Km for glycogen could be given because of complex kinetics in the presence of this substrate. The maltase activity was about 30% lower than the amyloglucosidase activity in islet tissue from NMRI mice. The reverse pattern was observed in the liver. Moreover, the liver amyloglucosidase activity was only one fourth of that of the islet tissue. The amyloglucosidase but not the maltase activity in islet tissue from CBA mice was lower than in islets from NMRI mice. Both activities were very low in islets from C-57 mice. A 24 hr fasting period reduced the amyloglucosidase but not the maltase activity in islets from NMRI mice. The insulin secretory response in vivo to an i.v. arginine load in the different strains and after fasting displayed the same pattern as the islet amyloglucosidase activity, whereas the insulin response following a glucagon injection was largest in the C-57 strain and unaffected by the fasting state. Pretreatment of mice with 0.05 mumol/kg of highly purified fungal amyloglucosidase, moderately (about 35%) enhanced the insulin secretory response to arginine, did not affect the response to glucagon, and greatly (about 100%) enhanced the response to glucose and tolbutamide. Moreover, treatment of mice with lysosomal stabilizers (glucocorticoids) reduced the insulin response to sulphonylureas and glucose, had no effect on the insulin response to beta-adrenergic and cholinergic stimulation, and increased ACTH-induced insulin release. A lysosomal labilizer (progesterone) enhanced the insulin response induced by glucose and tolbutamide.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1986

Effects of glipizide on various consecutive insulin secretory stimulations in patients with type 2 diabetes.

Immunoreactive insulin (IRI) and C-peptide secretory responses to consecutive stimulations with terbutaline, glucagon, glucose and a standard meal were investigated in fasted subjects with newly diagnosed, untreated Type 2 diabetes with and without concomitant administration of the sulphonylurea agent glipizide (5 mg). Basal concentrations of blood glucose were 8.7 +/- 0.8 mmol/l without glipizide, and 6.6 +/- 0.5 mmol/l with glipizide (p less than 0.01). This difference in prestimulation glucose levels persisted throughout the study. It was found that glipizide potentiated the IRI and C-peptide secretion in response to terbutaline (125 micrograms i.v.). The absolute IRI and C-peptide secretory responses to glucagon (250 micrograms i.v.) were of similar magnitudes with or without glipizide, despite the lower blood glucose concentrations after glipizide. Allowing for the lower blood glucose, IRI and C-peptide responses to glucagon were potentiated by glipizide. Glucose (6 g i.v.) exerted no IRI or C-peptide secretory effect in these patients either without or with glipizide. The changes in blood glucose concentration after injection of glucagon were not altered by glipizide. On the contrary, the terbutaline-induced increment in blood glucose concentration was inhibited by glipizide and the glucose elimination rate after glucose injection was slightly enhanced by glipizide; effects explained by the higher plasma insulin levels. After meal ingestion, the absolute IRI and C-peptide secretory responses were slightly enhanced by glipizide. Glipizide had no effect on the meal-induced changes in blood glucose concentrations. In conclusion, glipizide had the ability to cause an absolute potentiation of beta 2-adrenoceptor-stimulated and meal-induced insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Quinacrine accumulation in pancreatic islet cells of rat and mouse: relationship to functional activity and effects on basal and stimulated insulin secretion.

The fluorescent acridine derivative, quinacrine, was found to accumulate in rat and mouse pancreatic islet cells storing insulin, glucagon, pancreatic polypeptide, or somatostatin. Following administration of large doses of tolbutamide via an oro-gastric tube, the intensity of quinacrine fluorescence of insulin cells was substantially reduced. Similarly, the pancreatic insulin content was lowered. In contrast, the fluorescence intensity of the glucagon, pancreatic polypeptide and somatostatin cells appeared unaffected. Basal plasma insulin levels in the mouse were slightly elevated following quinacrine administration (25%). Glucose-stimulated insulin release was markedly enhanced (51%) in quinacrine-pretreated animals, whereas insulin release induced by cholinergic stimulation was unaffected. The results show that quinacrine accumulates in the various pancreatic islet cells. The drug seems to be confined to the secretory granules and affects the insulin response to glucose but not that to cholinergic stimulation, suggesting that these secretagogues act through different or partly different secretory pathways.

Animals↗

PubMed1985

Lysosomal enzyme activities in pancreatic islets from normal and obese hyperglycemic mice.

Lysosomal enzyme activities in pancreatic islets of obese hyperglycemic ob/ob mice aged 3 to 6 months were investigated and compared with those of normal lean NMRI mice of the same age. It was observed that the glycogenolytic glucose-producing hydrolase acid amyloglucosidase displayed a fivefold higher activity in the islets of obese mice than in the islets of normal NMRI mice. However, other islet lysosomal enzyme activities measured, such as N-acetyl-beta-D-glucosaminidase and beta-glucuronidase, were of the same magnitude in both obese and lean mice. A starvation period of 24 hours induced a significant depression of islet acid amyloglucosidase activity in obese as well as lean mice, whereas the activities of N-acetyl-beta-D-glucosaminidase and beta-glucuronidase were unaffected. Further, the activities of other types of islet lysosomal enzymes, such as acid phosphatase and cathepsin D, were also measured in obese mice. These activities were not found to be affected by the actual fasting period. A good correlation (r = 0.815; P less than 0.01) was observed between islet acid amyloglucosidase activity and plasma insulin concentrations in obese mice, whereas no such relationship was apparent with regard to other islet lysosomal enzyme activities recorded. Acid amyloglucosidase activity in liver tissue of the obese mouse was about 30 times lower than that of islet tissue. Further, the activity of liver amyloglucosidase was of the same order of magnitude in obese and lean mice. Similarly, other lysosomal enzyme activities in the liver of obese and lean mice were not strikingly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗