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Biomedical subjects

K Asplund

Publications and source records attributed to K Asplund.

At least 199 records · Page 11Linked to original sources

[32P] Orthophosphate efflux from pancreatic islets: graded response to glucose stimulation.

The dose-response relationships of the glucose-induced rapid transient efflux of [32P] orthophosphate from prelabeled pancreatic islets ("phosphate flush") have been investigated. Threshold levels for eliciting a "phosphate flush" were between 0.5 and 1.0 mg/ml glucose, the apparent "Km" for this event was 1.0-1.5 mg per ml and the apparent "Vmax" was reached at ambient glucose concentrations between 1.5 and 2.0 mg per ml. This dose-response curve is somewhat shifted to the left in comparison with previously published data for glucose-induced insulin release. Thus, the "phosphate flush" appears to display a more narrow dose-response curve to ambient glucose concentrations than the actual release of insulin. It is proposed that this may constitute further evidence that the "phosphate flush" reflects an early step in stimulus-secretion coupling and that there may be some loss of sensitivity as the glucose signal is transmitted from the site of recognition to the final site of hormone release.

Animals↗

Protein synthesis and amino acid accumulation during development in the rat: dissociation of diaphragm and heart muscle sensitivity to insulin.

Insulin is released into the circulation early during fetal life, but the physiological significance of the hormone in the fetus is still unclear. The present study was undertaken to evaluate the possible effects of insulin on the protein metabolism of skeletal and heart muscle during the perinatal period in the rat. When incubating hemidiaphragm in a bicarbonate buffer, 0.1 U/ml ox insulin failed to enhance the incorporation of leucine-4,5-3H into muscle protein before birth and during the immediate neonatal period. From 3 days of age onwards a stimulatory effect of insulin on protein synthesis was constantly observed. While insulin thus was ineffective in promoting protein synthesis in hemidiaphragms before the third postnatal day, it significantly enhanced the synthesis in heart muscle at an earlier stage of development. Insulin stimulated the uptake of alpha-aminoisobutyric acid-1-14C into the diaphragm muscle during late fetal life as well as through the early neonatal period. The role of insulin in protein metabolism during fetal life may thus be limited to the augmentation of amino acid transport in skeletal and heart muscle and to a stimulatory effect on protein synthesis only in certain tissue(s), e.g. heart muscle.

Aging↗

Decreased cyclic AMP and insulin response to glucose in isolated islets of neonatal rats.

The (3H) cyclic AMP accumulation was measured in incubations of pancreatic islets from one-day, six-day, and thirty-five-day-old rats exposed to a low (0.6 mg./ml.) or a high (3.0 mg./ml.) glucose concentration with or without the addition of 0.1 mM. of the phosphodiesterase inhibitor 3-isobutyl- 1 -methylxanthine (IBMX). In the thirty-five-day-old rats, (3H) cyclic AMP accumulation was significantly enhanced after sixty minutes' incubation in a high glucose concentration and further increased by IBMX. These changes were paralleled by a stimulated insulin release, measured simultaneously. By contrast, in the one-day-old rats, no effect of glucose with or without IBMX was seen on (3H) cyclic AMP, while the minor insulin release due to high glucose alone was markedly potentiated by IBMX. Even in the presence of this agent the insulin response to glucose was, however, clearly inferior to that seen in the thirty-five-day-old animals. The stimulatory patterns of glucose-induced insulin release in the six-day-old animals was intermediate between the other two age groups. At this age, stimulation of (3H) cyclic AMP due to glucose was observed only in the presence of IBMX. Measurement of (3H) cyclic AMP after three minutes' incubation confirmed these different stimulatory patterns of glucose in the age groups studied. It is suggested that the inefficiency of glucose to stimulate the adenyl cyclase-cyclic AMP system of the beta cell from fetal and neonatal animals may be one important factor determining the insensitivity to the insulin-releasing action of glucose that exists at this stage of development.

Adenylyl Cyclases↗

Transferrin types, iron-binding capacity and body iron stores.

Increased body iron stores and transferrin (TF) variants have been found to be associated with adverse health effects believed to be caused by oxygen free radicals. Previous attempts to establish a relationship between TF types, serum TF concentrations and iron-binding have been inconclusive. We have studied serum iron, total iron-binding capacity (TIBC), TF saturation and serum ferritin in relation to genetic TF types in a population sample (691 females and 639 males) from northern Sweden in an attempt to elucidate whether individuals with TF variants associated with adverse somatic and reproductive effects (TFC2 and C3) have increased body iron stores. As expected there was a highly significant sex difference, males manifesting increased body iron stores viz. increased levels of serum iron, TF saturation and serum ferritin, and a lower TIBC. There was no consistent and statistically significant association between the TFC2 variant and the parameters that indicate iron binding and storage. Thus the associations between TFC2 and somatic and reproductive damage appear to be independent of iron binding and body iron stores. TIBC (and TF levels) showed significant differences between TF types in females (p = 0.0015) but not in males. In females the TFC3 variant was associated with a significantly lower (p = 0.002) TIBC value. This decreased TIBC value was, however, not accompanied by an increased ferritin value, thus there was no unequivocal evidence for an association between TFC3 and increased body iron stores.

Alleles↗

Population studies in northern Sweden. 18. Geographical covariation between hypercholesterolemia and Finnish genetic influence.

The population of northern Sweden shows a marked ethnic heterogeneity and a unique distribution of disorders with a monogenic or polygenic background, among them cardiovascular diseases. We have studied variations between 23 North Swedish subpopulations (regions) with respect to hypercholesterolemia and its possible determinants including dietary factors, obesity and the degree of Finnish genetic influence. A significant regional heterogeneity was found concerning hypercholesterolemia, obesity and high consumption of 'boiled' coffee. Hypercholesterolemia showed significant geographical covariations with Finnish genetic influence and consumption of 'boiled' coffee. The results are consistent with the hypothesis that in addition to environmental factors Finnish genetic influence contributes to the development of hypercholesterolemia and thereby to the increased rate of cardiovascular disease found in northern Sweden.

Adult↗

Long-term outcome in cerebrovascular disease in relation to findings at aortocervical angiography. A 12-year follow up.

The natural history of cerebrovascular disease (CBVD) was evaluated in 169 non-treated patients followed for at least 12 years after aortocervical angiography. The outcome was related to type and location of atherosclerotic changes in the neck vessels. At the time of angiography, 108 patients had completed strokes, 20 had transient ischemic attacks (TIAs), and 41 had angiography for reasons other than acute CBVD. In patients with stroke, non-stenotic lesions as well as stenoses/occlusions were associated with a better long-term survival when they affected the vertebral territory than when the carotid arteries were involved. Patients with normal angiograms had no better prognosis than those with non-stenotic atherosclerosis. Only 2 of 12 deaths in patients with lesions in the vertebral artery were caused by cerebrovascular accidents. In all other groups (normal, carotid lesions only, changes in both carotid and vertebral arteries) the majority of deaths were attributed to CBVD. Rates of recurrent stroke were relatively low in patients with changes in the vertebral arteries and in subjects with non-stenotic lesions in one carotid artery. Intermediate rates were observed when the angiograms were normal, high rates when compound lesions had been demonstrated at angiography. Results show that in patients with stroke the location of atherosclerotic changes to different vessel territories appears to predict the clinical course better than the extent of the lesion(s). No specific angiographic finding was associated with a high initial and a low rate of stroke recurrencies. Therefore, drug therapy to prevent recurrent stroke must probably be life-long in all patients with CBVD not treated by surgery.

Adult↗

A randomized controlled trial of hemodilution therapy in acute ischemic stroke.

Rapid hemodilution in the early phase of ischemic stroke by the combination of venesection (250-650 ml during the first 2 days) and administration of low-molecular weight dextran was evaluated in a prospective controlled trial. Fifty-two patients were randomized to hemodilution therapy and 50 to a control group; the two groups were comparable in important prognostic variables. Mean hemoglobin was reduced from 147 to 127 g/l, hematocrit from 43 to 37% and, in a subsample of patients, whole-blood viscosity at a shear rate of 23 sec-1 from 7.0 to 4.3 cps over the first 2 days. Hemodilution was then maintained by repeated dextran infusions. Of the hemodiluted patients, 85% improved in neurological scoring over the first 10 days as compared to 64% of the control patients (p less than 0.025). The case fatality rate during the first 3 months was little affected by hemodilution. Among the survivors, 8% of the hemodiluted and 31% of the non-hemodiluted patients were unable to walk at 3 months. The proportion of surviving patients still hospitalized at the 3-month follow-up was 13% in the hemodilution group and 39% in the control group (p less than 0.01). The combination of venesection and dextran 40 administration is thus an unsophisticated but effective way to achieve rapid hemodilution in patients with acute cerebral infarction, and it improves the overall clinical outcome over the first 3 months.

Aged↗