PubMed Health⌕ Search

Biomedical subjects

J Iversen

Publications and source records attributed to J Iversen.

At least 55 records · Page 3Linked to original sources

Insulin sensitivity in alcoholic cirrhosis.

The amount-of-substance rate of glucose metabolism and its sensitivity to the concentration of insulin was quantified in 10 non-diabetic patients with alcoholic cirrhosis of varying severity, using the 'glucose clamp technique'. Fasting glucose and insulin were 5.4 +/- 0.3 mmol/l and 187 +/- 50 pmol/l (mean +/- SEM), respectively. During the hyperglycaemic clamp (blood glucose at 12.5 mmol/l) the glucose metabolic rate (divided by body mass) was 27 +/- 4 mumol X min-1 X kg-1 at an insulin concentration of 998 +/- 158 pmol/l. Thus the insulin sensitivity of the tissue glucose metabolism was 22 +/- 7 m3 X min-1 X kg-1. During the euglycaemic clamp exogenous insulin was given to a concentration of 574 +/- 72 pmol/l. The resulting glucose metabolic rate was 20 +/- 4 mumol X min-1 X kg-1 and the insulin sensitivity the same as during hyperglycaemia. The calculated systemic delivery rate of insulin (divided by body surface area) was 783 +/- 172 pmol X min-1 X m-2. Fasting glucagon was 32 +/- 5 pmol/ and only partly depressed by glucose or insulin. In comparison with stated relevant control groups cirrhotics exhibit glucose intolerance characterized by decreased sensitivity to insulin, hyperinsulinaemia due to increased release, and hyperglucagonaemia with decreased suppressibility. There was no relation between clinical or biochemical data of the patients and the above results, suggesting that the abnormal glucose metabolism does not depend directly on the decreased liver function but on a disturbed pancreatic-hepatic-peripheral axis.

Aged↗

The Ibc protein fraction of group B streptococci: characterization of protein antigens extracted by HCL.

The Ibc protein fraction of group B streptococci was prepared by HCL extraction of the type Ic strains A909 and 335. The fraction from strain A909 contained two protein antigens (alpha A 909 and beta A909) that could be separated by ion-exchange chromatography and isoelectric focusing. The 335 extract contained the alpha (alpha 335)-but not the beta antigen. The alpha 335 antigen was purified by similar procedures. The beta A909 antigen had a molecular weight of several hundred thousands, was immunogenic in rabbits and dissociated into several polypeptides on SDS-PAGE. Polypeptides with sub-unit molecular weights corresponding to 70,000 daltons showed antigenic activity. The alpha 335 antigen had a molecular weight of approximately 75,000 daltons as judged from gel filtration and SDS-PAGE. The antigen was immunogenic in rabbits. In contrast, the alpha A909 antigen showed neither protein lines on SDS-PAGE, nor immunogenicity in rabbits. However, the two alpha antigens showed serological crossreactivity in tests with the anti-alpha 335 serum.

Animals↗

Characterization of the inhibitory effect of somatostatin upon insulin and glucagon release in the isolated perfused canine pancreas: evidence for interaction with calcium.

Somatostatin is a potent inhibitor of insulin and glucagon release from the isolated perfused canine pancreas. The present investigation was undertaken to characterize the pancreatic effects of somatostatin by studying its ability to influence insulin and glucagon release from the same perfusion preparation in response to various well-known stimuli and modulators. Somatostatin inhibited insulin and glucagon release in all test situations chosen but one. Thus, somatostatin inhibits pancreatic hormone secretion irrespective of whether it is modulated by (1) a primary initiator of insulin release--glucose (1.3 or 8.3 mM), leucine (4.1 mM), tolbutamide (2.6 mM); (2) a potentiator of insulin release, i.e., a substance that requires the presence of glucose--arginine (1 mM); (3) substances known to increase the level of cyclic AMP (cAMP) in the islets--glucagon (2 ng/ml), cAMP (1 mM), theophylline (1 mM); (4) an autonomic agent--epinephrine (2 ng/ml), acetylcholine (10 microM); or (5) alpha and beta adrenergic antagonists--phentolamine (1 microM), propranolol (1 microM). In contrast, high Ca++ concentrations (4.8 and 8.2 mM) abolished the inhibitory action of somatostatin on both insulin and glucagon release. These findings lend support to the hypothesis that somatostatin acts at a stage of secretory processes, possibly related to Ca++ inactivation, late in the chain of events leading to hormone release.

Animals↗

Pancreatic polypeptide, glucagon and insulin secretion from the isolated perfused canine pancreas.

The release of pancreatic polypeptide (PP) by gut hormones, acetyl choline and adrenaline was investigated in an isolated perfused pancreas preparation. PP was potently released by 1 nmol/1 caerulein (186 +/- 12%, p is less than 0.001) and gastric inhibitory peptide (GIP) (211 +/- 31%, p is less than 0.005) as well as by 1 mumol/1 acetyl choline (1097 +/- 59%, p is less than 0.001). A significant two-fold release of PP was also evoked by 1 nmol/1 vasoactive intestinal peptide (VIP) (129 +/- 38%, p is less than 0.02 and gastrin (108 +/- 25% p is less than 0.01). Insulin release, induced by high glucose concentration was enhanced by both GIP (210 +/- 38%, p is less than (0.01) and VIP (48 +/- 5%, p is less than 0.001). In addition GIP enhanced the release of glucagon by 179 +/- 18% (p is less 0.001) at 1.4 mmol/1 glucose and by 127 +/- 24% (p is less than 0.005) at 8.3 mmol/1 glucose. Thus no simple inter-relationship appears to exist between the control of the three circulating islet hormones.

Acetylcholine↗

Dual action of mn++ upon the secretion of insulin and glucagon from the isolated, perfused canine pancreas. Possible interactions with ca++.

Since Mn++ apparently interferes with excitation-contraction coupling by both reducing inward movement of Ca++ across the cell membrane and by displacing Ca++ from an intracellular store, studies were performed in the isolated, perfused canine pancreas to elucidate the existence of a similar effect in stimulus-secretion coupling and to draw comparisons with the effect of Mg++, which antagonizes Ca++ at the cell membrane. The results show: 1. than Mn++ (0.05, 0.125, and 0.25 mmol/l) inhibits the release of insulin and glucagon in a dose dependent fashion during the first 3-4 min of infusion followed by a dose-dependent increase in hormone release, the 'escape phase'. 2. The inhibitory action of Mn++ (0.25 mmol/l) upon release of both hormones is progressively counteracted when perfusate calcium is increased from 0.7 to 1.3 to 5.0 mmol/l. 3. Mg++ (5 mmol/l) inhibits the release of both hormones with no sign of an 'escape phase'. 4. Mn++ (0.5 mmol/l) during calcium depletion causes a gradual stimulation of the release of both hormones. The dual action of Mn++ upon hormone release from the endocrine pancreas suggests that Mn++ can cross the cell membrane and can interfere with stimulus-secretion coupling both at the membrane level, by competitively inhibiting the Ca++ influx, and at some intracellular level by releasing calcium from an intracellular store.

Animals↗

Intranasal exposure of the Richardson's ground squirrel to Western equine encephalomyelitis virus.

Adult Richardson's ground squirrels were infected with western equine encephalomyelitis virus by intranasal instillation. Mortality followed the instillation of a minimum threshold of 4.7 logs of virus while infection was produced by a dosage of 2.3 logs. The incubation period was from four to seven days, being preceded by a viremic phase. Signs were depression, ataxia and paralysis of the limbs. Highest titres of virus were recovered from the brain and histopathological changes involving the central nervous system included meningitis, vasculitis, perivascular cuffing, gliosis, neuronophagia and neuronal degeneration. The virus was also found in a variety of extraneural tissues. Lesions in extraneural tissues included necrosis of brown fat and an apparent increase in number of Kupffer's cells in the liver. The lymphoid tissue was involved indicating a possible source for viremia. The duration and magnitude of viremia were ample enough to provide virus source for arthropods. The potential for transmission of the virus independent of arthropods was discussed in view of the pathogenesis demonstrated in the experimental infections.

Animals↗

Effect of Verapamil on pancreatic glucagon release from the isolated, perfused canine pancreas.

The effect of Verapamil, a potent calcium antagonist, upon pancreatic glucagon release was investigated in the isolated, perfused canine pancreas. Verapamil at concentrations ranging between 10(-5)-10(-4) mol/l caused a dose-related inhibition of glucagon release at a glucose concentration of 25 mg/dl. The inhibition was an immediate and reversible phenomenon. The inhibitory effect was reduced when the Ca2+ concentration was increased from 1.3 to 5.0 mmol/l. The results are compatible with earlier findings from our laboratory demonstrating that calcium plays a key role in the stimulus-secretion coupling of glucagon release.

Animals↗

Failure of somatostatin to correct manifest diabetic ketoacidosis.

Juvenile diabetic patients were studied 60-72 hours after insulin withdrawal when moderate ketoacidosis had developed. Somatostatin infusion for 4 hours in five patients resulted in almost complete suppression of plasma pancreatic glucagon and growth hormone, a fall in plasma-cyclic-adenosine-monophosphate (A.M.P.) concentrations, and a large fall in plasma-glucose concentration. After infusion plasma concentrations of these substances rose again. Blood-ketone-bodies, plasma-free-fatty-acids (F.F.A.), and plasma glycerol concentrations, however, did not decrease appreciably with somatostatin administration. In three patients 2 to 3 h somatostatin infusions were twice superimposed upon a continuous 9-5 h insulin infusion (1 unit/h). An insulin effect was noticeable within 30 minutes, with pronounced falls in the concentrations of plasma glucose, pancreatic glucagon, F.F.A., and blood-ketone-bodies. There was no significant change in these patterns when somatostatin was administered or withdrawn. These results do not indicate that somatostatin infusion would be useful in the treatment of manifest diabetic ketoacidosis.

Adult↗

Subcutaneous exposure of the Richardson's ground squirrel (Spermophilus richardsonii Sabine) to western equine encephalomyelitis virus.

Both adult and suckling Richardson's ground squirrels (Spermophilus richardsonii) were susceptible to subcutaneous exposure with western equine encephalomyelitis (WEE) virus, but the virus was more virulent for sucklings than adults. In sucklings, the incubation period was from 4 to 5 days, followed by apparent signs of central nervous system (CNS) involvement. Death occurred 10 to 13 days postexposure. In adults, infections were inapparent or acute with typical signs of CNS involvement similar to those observed in sucklings. In both age groups, brain and lymph nodes were the most frequently involved tissues. The highest titres of virus were recovered from brain, sections of which also showed the most marked histological changes. Lesions in the brain included multifocal vasculitis, perivascular edema, perivascular cuffing, focal or diffuse gliosis, parenchymal hemorrhage, meningitis with infiltration of mononuclear cells, neuronal degeneration, and occasional demyelination. For both age groups, viremias were detected for 3 to 5 days with a maximum virus titre of 4 to 6 logs, a sufficient time and magnitude to infect numerous mosquitoes, further supporting the hypothesis that S. richardsonii may serve as an amplifying host of WEE virus in the prairie provinces.

Animals↗

Demonstration of a class of proteins loosely associated with secretory granule membranes.

It is shown, in this study, that rat secretory granule membrane preparations, as prepared by the method of Amsterdam et al. [(1971) J. Cell Biol. 50, 187-200], contain a protein fraction which is removed by washing in isotonic medium. This fraction contains unusually high levels of Pro, Gly and Glx, and appears to label rapidly if the rats are pulsed with [14-c] amino acids prior to removal of the glands. The fraction, which may represent specifically adsorbed secretory protein(s) or peripheral membrane protein, is significant to investigators using this model system to study secretory phenomena.

Amino Acids↗

The protein composition of rat parotid saliva and secretory granules.

Rat parotid saliva was collected by surgical cannulation of the ducts and stimulation with pilocarpine; The secreted salivary proteins were resolved on columns of DEAE-Sephadex into five major Fractions, I-V, which were characterized by polyacrylamide disc gel electrophoresis, amino acid analyses and enzymatic assay. Rat parotid secretory granules were isolated by density gradient centrifugation and lysed in hypotonic buffers. Granule content proteins were resolved and examined by the same techniques as for secreted proteins. In both experiments, Fraction I contained RNAase and a major unidentified protein, M1, Fraction II contained the isoenzymes of amylase; DNAase was present in Fraction III and, to a lesser degree, in Fraction IV. The proportions of the enzyme-containing peaks were the same in saliva and granule contents. Fractions IV and V contain proteins of unknown function; Fraction IV contains exceptionally high levels of glutamic acid, glycine and proline in its protein moieties and approx. 6-8% neutral sugars.

Amino Acids↗