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Biomedical subjects

I Lundquist

Publications and source records attributed to I Lundquist.

At least 91 records · Page 5Linked to original sources
PubMed1985

Effects of alpha- and beta-adrenoceptor stimulation on 45Ca2+ efflux and insulin secretion from perfused rat islets.

Exposure to the beta 2-adrenoceptor agonist terbutaline resulted in a transient stimulation of 45Ca2+ efflux from 45Ca2+ preloaded rat islets perfused in 2 mM Ca2+ and 8.3 mM glucose. Concomitantly, an increase in insulin secretion occurred. Under the same experimental conditions, the alpha-adrenoceptor agonist noradrenaline promptly inhibited insulin release without any apparent influence on 45Ca2+ efflux. In contrast, in a medium containing 2 mM Ca2+ and a low glucose concentration (2.8 mM), terbutaline stimulated insulin secretion without any apparent effects on 45Ca2+ efflux. Noradrenaline had no effect on insulin secretion or 45Ca2+ efflux in this medium. When islets were perfused with 8.3 mM glucose in a Ca2+ deficient medium, with or without addition of the chelating agent EGTA, terbutaline induced a marginal stimulation of insulin secretion and a negligible stimulation of 45Ca2+ efflux. On the contrary, noradrenaline stimulated to an immediate and notable 45Ca2+ efflux in these Ca2+ deficient media. Noradrenaline also clearly inhibited insulin secretion, though less markedly and with a slower onset than in islets perfused in 2 mM Ca2+. When the islets were perfused in a Ca2+ deficient medium with 2.8 mM glucose, terbutaline had a slight insulin releasing effect, but stimulated 45Ca2+ efflux potently. Noradrenaline had no influence on insulin secretion but a weak stimulatory effect on 45Ca2+ efflux. The data suggest that the beta 2-adrenoceptor agonist terbutaline has the ability to stimulate insulin secretion in perfused rat islets, requiring extracellular Ca2+ for the full expression of its effects. These effects may be exerted through a Ca2+-Ca2+ exchange over the cell membrane and/or through cAMP and intracellular Ca2+ perturbations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1985

Effects of alpha-adrenoceptor blockade by phentolamine on basal and stimulated insulin secretion in the mouse.

The sympathetic nervous system is known to innervate the pancreatic islets and to have the capability to influence islet hormone release. The effects are, however, complex since the islet nerves contain catecholaminergic as well as peptidergic fibres, and the catecholamines stimulate alpha- as well as beta-adrenoceptors. The present study was undertaken to establish the possible influence of the alpha-adrenoceptors on basal and stimulated insulin secretion under in vivo conditions. The alpha-adrenoceptor blocker phentolamine was injected at various dose levels i.p. to mice and a dose-dependent increase in plasma concentrations of insulin was seen. The maximal plasma insulin levels were observed 10 min after injection and were accompanied by decreased plasma glucose concentrations. Additionally, plasma glucose levels fell in response to phentolamine by an apparent insulin-independent manner, since at the low dose of 2.6 mumol kg-1, plasma glucose levels did decrease without any apparent increase in plasma insulin levels. After injection of a low dose of phentolamine 10 min prior to a rapid i.v. injection of one of four different insulin secretagogues, the following effects on insulin release were observed. Glucose (+55%) and the cholinergic agonist carbachol (+140%) displayed a potentiated insulin secretory response after phentolamine pretreatment, whereas the beta 2-adrenoceptor agonist terbutaline (-45%) had a blunted, though not abolished, insulin response. The absolute insulin secretory response to CCK-8 was unaffected by phentolamine despite the fact that plasma glucose levels were lowered by phentolamine. In conclusion, phentolamine enhanced insulin secretion and depressed plasma glucose levels in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1985

Effects of L-dopa-induced dopamine accumulation on 45Ca2+ efflux and insulin secretion in isolated rat islets.

It has previously been demonstrated in several species that the secretory granules of pancreatic beta-cells have the ability to store substantial amounts of calcium and bioactive amines, such as dopamine and serotonin. Furthermore, evidence for a similar topographical localization for amine and calcium within the periphery of the granules has been obtained. In the present study, a possible interaction between dopamine and calcium on insulin release was investigated. Isolated rat islets were loaded with 45Ca2+ in the presence of theophylline and high glucose and then perifused in a dynamic system where radioactivity and insulin were determined in the effluent. When perifused in a bicarbonate buffer with 2 mmol/l Ca2+ and supplemented with the monoamine oxidase inhibitor pargyline, L-3,4-dihydroxyphenylalanine (L-dopa)-induced dopamine accumulation in the islets brought about a slight and transient increase in 45Ca2+ efflux. This increase was more pronounced and sustained in a Ca2+-deficient buffer or in a Ca2+-deficient buffer supplemented with ethyleneglycolbis(aminoethylether)tetraacetic acid (EGTA). Insulin release was transiently stimulated by islet dopamine accumulation in the Ca2+-deprived media, but not in a medium with 2 mmol/l Ca2+. Glucose-induced insulin release in 2 mmol/l Ca2+ was potentiated by acute dopamine accumulation. The combined effect of glucose stimulation and islet accumulation of dopamine induced a transient insulin release in the Ca2+-deprived media with and without EGTA. This release of insulin was accompanied by an increased 45Ca2+ efflux which was most pronounced in the presence of EGTA. Stimulation with glucose alone, i.e. without addition of L-dopa tended to decrease insulin release and 45Ca2+ efflux in a Ca2+-deficient medium. No effects of L-dopa or L-dopa + glucose were encountered in a Ca2+-deficient buffer when the monoamine oxidase inhibitor pargyline was replaced by the dopa-decarboxylase inhibitor benserazide. The results are interpreted as being a consequence of a complex interaction between the accumulated dopamine and a pool of Ca2+ mainly confined to the secretory granules. This interaction could be followed by a transient increase in cytosolic Ca2+ and a subsequent efflux of Ca2+ out of the cell, eventually accompanied by insulin release. Increasing the cytosolic Ca2+ by acute dopamine accumulation makes the cell more sensitive to a concomitant stimulation with glucose, and the release of insulin is triggered. A long-term dopamine accumulation. On the other hand, might diminish the granular Ca2+ pool to such a level where insulin release is inhibited after stimulation with certain secretagogues.

Animals↗
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↗
PubMed1985

Hormonal and metabolic responses to breakfast meals in niddm: comparison of white and whole-grain wheat bread and corresponding extruded products.

The post-prandial glucose and hormonal responses were followed in nine non-insulin-dependent diabetics after four randomized breakfast meals containing mainly wheat products. The effect of conventionally baked breads was compared with extruded crispbread-like products prepared from white or whole-grain wheat flour, respectively. The extruded whole-grain product gave significantly larger areas under the glucose and insulin curves than the corresponding baked bread, and resulted in higher C-peptide, gastric inhibitory polypeptide, and glucagon concentrations at certain time points. The mean incremental areas under the glucose curves were similar after white bread and the two extruded crispbread-like products. There were no significant differences between white and whole-grain bread. The results indicate that baked whole-grain wheat bread is to be preferred to corresponding extruded products in non-insulin-dependent diabetes mellitus.

Adult↗
PubMed1985

Islet lysosomal enzyme activities and plasma insulin levels in obese hyperglycemic mice following injection of the lysosomotropic drug suramin.

The pattern of islet lysosomal enzyme activities and the plasma levels of insulin and glucose were studied in adult obese hyperglycemic mice (aged 6-8 months) after in vivo administration of the lysosomotropic drug suramin. After suramin administration, 5.2 mumol/mouse, at time 0 and at 18 hr, the plasma insulin levels in the obese mice gradually decreased and were reduced by about 85% at 20 hr. At the same time point the suramin-induced inhibition of insulin secretion was reflected by a notable (250%) increase in islet insulin content. A negative correlation (r = -0.81; p less than 0.01) was observed between plasma insulin level and islet insulin storage. The plasma glucose levels were not affected by the drug. Furthermore, it was observed that the islet activity of the glucose producing glycogenolytic hydrolase, acid amyloglucosidase, which is excessively high in the obese mouse, was markedly reduced by suramin (about 70%) at 20 hr. A good correlation (r = 0.88; p less than 0.001) was found to exist between the islet acid amyloglucosidase activity and the plasma insulin concentration in controls and suramin-treated mice. When glycogen was replaced by maltose or 4-methylumbelliferyl-alpha-D-glucoside as substrate for the acid alpha-1,4-glucoside splitting activity the inhibitory effect of suramin was less pronounced (about 50%). The ratio, glycogen splitting/maltose splitting activity in islet tissue was reduced by suramin from 1.25 +/- 0.12 (control) to 0.69 +/- 0.06 (p less than 0.005). The neutral, nonlysosomal alpha-1,4-glucoside splitting activity was not affected by the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

High frequency of natural autoantibodies in normal newborn mice.

Spleen cells from 6-day-old nonimmunized BALB/c and BALB.B10 mice were fused with the nonsecreting hybridoma cell line Sp2/0. Three hundred and eighty-four immunoglobulin-secreting hybrids were screened for antibody activity against mouse actin, tubulin, and myosin, and against TNP, peroxidase, renin, DNA, and neurofilaments. At least 24 hybridomas in the collection (6.25%) exhibited antibody activity against this panel of antigens. Ten of these hybrids were cloned, were propagated, and the corresponding monoclonal IgM protein was isolated from ascitic fluids and was further characterized. At least four groups of antibody specificities were identified: 1) one clone reacting with TNP only; 2) one clone reacting with both actin and tubulin; 3) two clones which bound to both TNP and actin; and 4) a fourth group, comprising the six other clones, which all exhibited widespread reactivity and bound to actin, tubulin, myosin, and TNP. These results indicate: 1) B cell clones directed against self antigens are activated in the internal environment and are recovered consequently by somatic cell hybridization; 2) the widespread antibody specificities found for these newborn mouse antibodies are very similar to those previously characterized with human natural antibodies and human monoclonal Ig; and 3) the frequency of B cells binding to cytoskeletal proteins and TNP is very high (at least 6.25%).

Animals↗
PubMed1984

Effects of naloxone on basal and stimulated insulin secretion in the mouse.

Endogenous opiates have been suggested to have effects on insulin secretion. In order to investigate the in vivo importance of endogenous opiate receptor agonists on basal and stimulated insulin secretion, the effect on plasma insulin of opiate receptor blockade by naloxone was studied in the mouse. It was found that the plasma insulin levels in naloxone-injected mice were moderately lower than in the control animals after 5 min. Ten minutes later, however, naloxone-injected animals had slightly higher plasma insulin levels than did the controls. Naloxone moderately potentiated the insulin secretory responses to glucose and the beta 2-adrenoceptor agonist terbutaline. On the contrary, naloxone had no apparent effect on the insulin secretory response to the cholinergic agonist carbachol or the synthetic C-terminal octapeptide of cholecystokinin, CCK-8. In conclusion, endogenous opioid substances might moderate the regulation of basal insulin levels in the mouse. Further, they seem to have the capability to modulate the insulin release stimulated by glucose or beta-adrenoceptor agonists.

Animals↗
PubMed1984

Effect of dietary fibre on blood glucose, plasma immunoreactive insulin, C-peptide and GIP responses in non insulin dependent (type 2) diabetics and controls.

A high fibre and a low fibre breakfast meal were given to eight non insulin dependent diabetics ( NIDD ), and eight controls. Blood glucose response was monitored continuously for three hours and characterized using a straight line model. After the high fibre meal the rates of increase and decrease in blood glucose concentration were slower both in diabetics and controls than after the low fibre meal. The delay time, however, i.e. the time from meal intake to the start of glucose increase, hypothetically corresponding to gastric emptying time, was the same after both test meals. The postprandial glucose increment calculated as the area under the 0-120 min curve was lower after the high fibre meal in the NIDD , but not in the controls. The two-hour C-peptide and gastric inhibitory polypeptide values were lower for the diabetics after the high fibre breakfast. The results indicate a prolonged carbohydrate digestion and/or absorption after high fibre breakfast.

Adult↗
PubMed1984

Influence of intraluminal trypsin activity on the course of acute experimental pancreatitis.

In short-term experiments (25 or 72 h) oral trypsin inhibitor administration to pancreatitic rats significantly decreased survival rate, whereas oral trypsin administration had no effect in this respect. Neither treatment influenced the activities of amylase in serum, pancreatic tissue or ascites. Trypsin given in excess together with the trypsin inhibitor abolished the deleterious effects on survival caused by the trypsin inhibitor. In a long-term experiment in healthy rats oral trypsin inhibitor ingestion caused a significant increase in pancreatic wet weight, protein concentration and activities of amylase, lipase and trypsinogen in pancreatic tissue; again, trypsin administration had no effect. The data support the idea that oral trypsin inhibitor administration causes release of cholecystokinin (CCK) or CCK-like factors from the intestine by interfering with the negative feedback regulation exerted by intraluminal trypsin. The results of the short-term experiments further indirectly suggest that even small amounts of trypsin within the intestine - as in acute pancreatitis - can exert the feedback regulation. Finally, the results of the long-term experiment suggest that oral administration of trypsin does not exert any suppressive effects on pancreatic wet weight and pancreatic enzyme content.

Acute Disease↗
PubMed1984

Effects of alpha 1-, alpha 2- and beta-adrenoceptor blockers on insulin secretion in the rat.

The effects of alpha- and beta-adrenoceptor blockade on plasma concentrations of insulin and glucose were studied in the anaesthetized rat. Infusion of the alpha 1-adrenoceptor blocker prazocin (80 micrograms/min), the alpha 2-adrenoceptor blocker yohimbine (15 micrograms/min) or the non-selective alpha-adrenoceptor blocker phentolamine (15 micrograms/min) during 50 min increased plasma insulin levels by about 1.5-2.5 ng/ml. The effects of phentolamine and prazosin on circulating insulin persisted throughout the infusion whereas the effect of yohimbine seemed to be more transient. Plasma glucose levels increased slightly during infusion of prazosin, but tended to decrease in response to phentolamine and yohimbine. The beta-adrenoceptor blocker propranolol (15 micrograms/min) lowered basal plasma insulin and glucose levels. It also depressed plasma insulin during infusion of all three alpha-adrenoceptor blockers without any appreciable influence on plasma glucose. It is suggested that both alpha 1- and alpha 2-adrenoceptor as well as beta-adrenoceptors are involved in the regulation of basal insulin secretion in the rat.

Adrenergic alpha-Antagonists↗
PubMed1984

Effects of pectin and wheat bran on intraluminal pancreatic enzyme activities and on fat absorption as examined with the triolein breath test in patients with pancreatic insufficiency.

In totally pancreatectomized patients breath 14CO2 excretion after ingestion of 14C-labeled triolein was significantly increased by a granulated pancreatic enzyme preparation and was reduced when pectin was added to the enzyme supplement. In the same patients pectin reduced trypsin, lipase, and amylase activities of jejunal aspirates after a test meal supplemented with pancreatic enzyme substitution, which was shown to give good enzyme activities in the intestine. In patients with chronic pancreatitis, breath 14CO2 excretion was reduced by wheat bran, which also caused a reduction in lipase and amylase activities of duodenal aspirates after a test meal. The findings demonstrate the efficiency of treatment with a granulated pancreatic enzyme preparation in restoring intraluminal enzyme activities and fat absorption in patients with pancreatic insufficiency. They also show that pectin and wheat bran may induce fat malabsorption and inhibit digestive enzyme activities in vivo.

Adult↗
PubMed1983

Hormonal and cholinergic effects on amylase and lysosomal enzyme activities in pancreatic tissue and ascites of rats with acute experimental pancreatitis.

The effects of hormonal or cholinergic stimulation on survival and on activities of lysosomal enzymes and amylase in pancreatic tissue and ascites were studied in rats with induced pancreatitis. Pancreatitis per se caused an increase of the activities of cathepsin D, N-acetyl-beta-D-glucosaminidase and amylase, and a decrease of acid phosphatase in pancreatic tissue. Pancreatic protein concentration was not influenced. In pancreatitic rats administration of cerulein or carbachol markedly decreased survival rate. Cerulein increased the activities of cathepsin D and amylase in ascites and cathepsin D and acid phosphatase in pancreatic tissue. Carbachol increased the activities of cathepsin D and amylase in ascites and acid phosphatase in pancreatic tissue. Both cerulein and carbachol decreased the activity of amylase in pancreatic tissue. Administration of secretin or the anticholinergic drug Pro-Banthine did not influence survival rate or the activities of lysosomal enzymes and amylase in ascites. In pancreatic tissue the activity of acid phosphatase was slightly increased by secretin or Pro-Banthine. In conclusion, the results show a nonparallel alteration of lysosomal enzyme activities in pancreatic tissue in rats with pancreatitis. Cerulein and cholinergic stimulation decreased survival rate and brought about a marked increase of cathepsin D activity in ascites and, in the case of cerulein, also in pancreatic tissue. The implication of lysosomes and especially the catheptic proteases in the pathogenesis and outcome of acute pancreatitis deserves further attention.

Acetylglucosaminidase↗
PubMed1983

Effect of fasting on islet lysosomal enzyme activities and the in vivo insulin response to different secretagogues.

The effect of a 24 hr starvation period on islet lysosomal enzyme activities and the in vivo insulin response to glucose, glibenclamide and L-isopropyl-noradrenaline (L-IPNA) was studied in mice. It was observed that fasting induced a significant decrease of islet acid amyloglucosidase activity, whereas the activities of acid phosphatase, beta-N-acetyl-glucosaminidase, and beta-glucuronidase in islet tissue were unaffected by the fasting period studied. Starvation markedly reduced the acute insulin response to a maximal dose of glucose or glibenclamide. However, the insulin response to a maximal dose of L-IPNA was of similar magnitude in both fed and fasted animals. Pretreatment of fasted mice with purified fungal acid amyloglucosidase could restore the impaired insulin response to glucose to the normal level seen in fed mice. It is suggested that islet acid amyloglucosidase activity is of importance for glucose-stimulated insulin secretion, and that reduced levels of islet amyloglucosidase may contribute to the impairment of glucose-induced insulin release seen after fasting.

Acetylglucosaminidase↗
PubMed1983

Role of the kidneys in elimination of glucagon, insulin, secretin and somatostatin in the rat.

Immunoreactive plasma glucagon and secretin in the rat was elevated 48 hours after nephrectomy and ureteral ligation. Since kidneys obstructed by ureteral ligation were unable to remove glucagon and secretin from the blood, renal handling of glucagon and secretin must include glomerular filtration. Insulin and somatostatin levels were significantly elevated 48 hours after nephrectomy, but not after ureteral ligation, indicating partial uptake from peritubular capillaries.

Animals↗
PubMed1983

Influence of pancreatic duct ligation on endocrine and exocrine rat pancreas.

A parallel investigation into endocrine and exocrine pancreatic function, after duct-ligation in the rat, was performed to study the effect of reduced intestinal trypsin levels on insulin secretion and glucose tolerance. Animals with only a slight exocrine insufficiency displayed a normal insulin secretion and a normal glucose tolerance 4 weeks after operation. At 4-5 month s these animals showed a slight increase in glucose-induced insulin release when compared with control rats. However, animals operated on with a more complete ligation of the pancreatic ducts, who showed a marked exocrine insufficiency accompanied by decreased levels of intestinal trypsin, displayed a markedly increased insulin secretory response to intravenous glucose and an increased glucose tolerance. The results lend further support to our previous suggestion that, in the rat, the levels of intestinal trypsin may influence insulin secretory processes via complex feed-back mechanisms which may involve cholecystokinin and/or other intestinal hormones.

Amylases↗
PubMed1983

Effects on the exocrine and endocrine pancreas of duct occlusion with two different tissue glues in the rat.

Exocrine and endocrine pancreatic function was studied in the rat after occlusion of the pancreatic ducts with acrylate or prolamine, respectively. After 5 months the effect of these procedures was a clear-cut exocrine insufficiency as evidenced by reduced enzyme activities in pancreatic tissue and in intestinal content, while the endocrine function was not impaired. The insulin secretory response to an intravenous glucose load was rather increased in duct-occluded rats, and the glucose tolerance was improved. The liver glycogen levels in duct occluded rats were decreased. As judged from the present investigation there was no striking difference between the effects of acrylate and prolamine on either exocrine or endocrine pancreas. The results suggest that long-term duct occlusion in the rat by acrylate or prolamine is harmless to the endocrine pancreas. The improvement of the glucose-induced insulin response and the glucose tolerance is probably due to an enteropancreatic feedback mechanism elicited by low levels of intestinal trypsin.

Animals↗