Biomedical subjects

A M Svensson

Publications and source records attributed to A M Svensson.

12 recordsLinked to original sources

PubMed1997

Gastric inhibitory polypeptide and splanchnic blood perfusion: augmentation of the islet blood flow increase in hyperglycemic rats.

The aim of the study was to investigate how the incretin candidate hormone gastric inhibitory polypeptide (GIP) affects splanchnic blood flow, especially pancreatic islet blood flow. For this purpose, male Sprague-Dawley rats were injected intravenously with either saline or GIP (5 or 15 micrograms/kg body weight) 10 min before blood flow measurements by a microsphere technique. Furthermore, 3 min before the blood flow measurements, 1 ml of either saline or 30% D-glucose was given intravenously. All glucose-injected animals were markedly hyperglycemic (> 20 mmol/liter) at the time of the blood flow measurements. Both doses of GIP potentiated basal and glucose-stimulated insulin release. In the normoglycemic rats, the lowest dose of GIP did not affect the blood perfusion to any of the investigated organs. The highest dose of GIP decreased whole pancreatic and duodenal blood flow, whereas islet blood flow was unaffected. As a result, fractional islet blood flow was increased. In the hyperglycemic rats, where the islet blood flow was increased compared with control animals, both doses of GIP further enhanced islet blood flow. No effect on pancreatic, fractional islet, or duodenal blood flow was seen after GIP administration to hyperglycemic animals. It is concluded that administration of GIP can further augment the glucose-induced stimulation of islet blood flow. This may contribute to facilitating release of insulin from the islets.

Animals↗

PubMed1997

Prolactin regulation of islet-derived INS-1 cells: characteristics and immunocytochemical analysis of STAT5 translocation.

The major changes in pancreatic islet function during pregnancy and after exposure to lactogens are an increase in beta-cell proliferation and enhanced insulin secretion. In this study we examined INS-1 cells as a potential model for further inquiry into PRL signaling in beta-cells. Proliferation of beta-cells, insulin secretion, and quantitative immunocytochemical analysis of STAT5 translocation were studied. PRL treatment of INS-1 cells resulted in a 2- to 4-fold increase in cell proliferation compared to that in the control group. In contrast, there was no effect of PRL treatment on HIT cell proliferation and only a very small effect on RIN cell proliferation. A significant effect on INS-1 cell proliferation was observed at 10 ng/ml and reached a maximum at 200 ng/ml. PRL treatment resulted in enhanced insulin secretion from INS-1 cells. There was a time-dependent increase in insulin secretion, which when corrected for cell number was 1.5-fold greater in the PRL-treated cells. The effects of PRL on cell division and insulin secretion were glucose dependent. The presence of the JAK family of tyrosine kinases and the transcription factor STAT5 in INS-1 cells was examined by immunocytochemical techniques. Although all members of the JAK family of kinases were detected, the staining intensity of JAK-2 was noticeably more intense. Initial studies of STAT5 translocation were performed using PRL-dependent Nb2 lymphoma cells, in which PRL treatment resulted in a nearly complete translocation of cytoplasmic STAT5 to the nucleus. Under control conditions there was a near-equal fluorescence intensity of STAT5 staining in the nucleus and cytoplasm of INS-1 cells. PRL treatment resulted in a time-dependent increase in STAT5 staining in the nucleus, with a corresponding decrease in the cytoplasm. The STAT5 staining intensity in the nucleus remained elevated for the duration of PRL treatment. This effect was reversible upon removal of PRL from the medium. Besides PRL, both GH and FBS induced a similar translocation of STAT5 to the nucleus. Although present in RIN cells, no detectable changes in STAT5 were observed in RIN cells after exposure to PRL, GH, or FBS. INS-1 cells should provide a good model for further inquiry into the intracellular signaling pathways used by PRL and how these events alter islet function.

Animals↗

PubMed1996

L-arginine and pancreatic islet blood flow in anesthetized rats.

The aim of the present study was to see if L-arginine, which induces insulin release and is a precursor of the endothelial-derived relaxing factor nitric oxide, affects whole pancreatic and/or islet blood flow. For this purpose, anesthetized male Sprague-Dawley rats were injected intravenously with either saline or L-arginine (25, 100 or 250 mg/kg body weight). All doses of arginine caused a slight increase in blood glucose concentration, while the highest dose (250 mg/kg body weight) also increased insulin concentration. However, no changes in either mean arterial blood pressure, whole pancreatic or islet blood flow could be discerned with any of the doses of arginine used. It is concluded that insulin release is not necessarily associated with an increased islet blood perfusion.

Animals↗

PubMed1996

Diet-induced obesity and pancreatic islet blood flow in the rat: a preferential increase in islet blood perfusion persists after withdrawal of the diet and normalization of body weight.

The aim of the present study was to evaluate the effects of diet-induced obesity on pancreatic islet blood perfusion in normal Wistar rats. Furthermore, we investigated to what extent any obesity-associated changes in islet blood flow could be reversed after reversion to a normal diet with normalization of body weight. Young adult female Wistar rats were offered a palatable mixed high-caloric diet (cafeteria diet) in addition to standard pelleted chow. Age-matched control rats received standard pelleted chow only. After 4 weeks the diet-treated rats had a body weight of approximately 15% more than that of the controls. All diet-treated rats had decreased glucose tolerance and increased serum insulin concentrations, but basal blood glucose concentrations were similar in anesthetized diet-treated and control rats. Whole pancreatic and islet blood flow rates were measured with a microsphere technique. The islet blood flow as well as fractional islet blood flow were increased (P < 0.01) in rats fed the cafeteria diet, while blood perfusion of the whole pancreas was similar to that of the control rats. In a second experiment, rats received the cafeteria diet for 4 weeks and were then fed standard pelleted food alone for another 3 weeks, while controls received standard diet for 7 weeks. After this period total body weight, retroperitoneal fat pad weight and glucose tolerance were similar to those of the controls. Whole pancreatic blood flow was unchanged as compared with that of control rats. However, both islet blood flow (P < 0.01) and fractional blood flow (P < 0.01) were increased. We conclude that diet-induced obesity in rats is associated with decreased glucose tolerance, hyperinsulinemia and a specific increase in absolute and fractional islet blood perfusion. This increase persists for at least 3 weeks after the diet is withdrawn despite normalization of body weight and glucose tolerance.

Animals↗

PubMed1995

Dynamic on-line vectorcardiography improves and simplifies in-hospital ischemia monitoring of patients with unstable angina.

OBJECTIVES: This study sought to validate computerized vectorcardiography against the established technique of Holter electrocardiographic (ECG) monitoring and to compare the feasibility of the two methods for monitoring patients with unstable angina pectoris. BACKGROUND: Detection of myocardial ischemic episodes is an important objective in patients admitted to the hospital for unstable angina pectoris. Standard ECG monitoring may be sufficient for detection of symptomatic episodes but will often overlook silent ischemia. Holter ECG monitoring has a higher likelihood of discovering such episodes, but analysis is time-consuming, and the results are not available on-line. METHODS: We simultaneously monitored 53 consecutive patients with unstable angina, 46 of whom had technically adequate 24-h Holter ECGs and computerized vectorcardiograms. RESULTS: The Holter tapes had a mean (+/- SD) of 15.3 +/- 10.3 h of recording with both channels technically adequate for analysis compared with 23.7 +/- 1.77 h of vectorcardiographic recording that could be analyzed (p < 0.01). Of the 15 symptomatic episodes detected by Holter ECG monitoring, 13 were also detected with dynamic vectorcardiography. In contrast, eight patients had 18 episodes of chest pain, with simultaneous ST segment changes detected by dynamic vectorcardiography; only 9 of these episodes were also detected by Holter ECG monitoring. CONCLUSIONS: Monitoring of myocardial ischemia with dynamic vectorcardiography seems to be more efficient than Holter monitoring and may have a higher sensitivity. Computerized, continuous vectorcardiography has a complete real-time capacity, allowing monitoring over prolonged periods of time, and the results are immediately available without time-consuming analysis.

Adult↗

PubMed1995

The blood flow in pancreatico-duodenal grafts in rats: inhibition of nitric oxide synthase preferentially decreases islet blood flow.

In this study normoglycemic inbred Wistar-Furth rats were implanted with a syngeneic pancreatico-duodenal graft, i.e. a denervated pancreas. The blood flow to the intact native pancreas and to the transplanted gland was measured with a microsphere technique in anesthetized rats 2 weeks after transplantation. The animals were given an intravenous injection with saline alone, NG-nitro-L-arginine (25 mg/kg body weight) or sodium nitroprusside (10 micrograms/kg body weight) 10 min before blood flow measurements. Administration of NG-nitro-L-arginine increased mean arterial blood pressure and caused a pronounced decrease in whole pancreatic blood flow in both the native and transplanted gland. The islet blood flow was more markedly decreased by NG-nitro-L-arginine in both the native and transplanted pancreas, and constituted about 4% of whole pancreatic blood flow compared with 10% in the control animals. Sodium nitroprusside markedly decreased mean arterial blood pressure, but did not affect pancreatic or islet blood flow in any of the glands. It is concluded that inhibition of nitric oxide synthase causes a preferential decrease in islet blood flow both in the native pancreas and in the transplanted pancreas. This suggests that nitric oxide which affects islet blood flow is mainly endothelial-derived, and does not emanate from external nervous fibers.

Amino Acid Oxidoreductases↗

PubMed1994

Inhibition of nitric oxide synthase by NG-nitro-L-arginine causes a preferential decrease in pancreatic islet blood flow in normal rats and spontaneously diabetic GK rats.

To elucidate the effect of nitric oxide (NO) on the blood flow of the pancreatic islets, the NO synthase inhibitor NG-nitro-L-arginine (N-arg; 25 mg/kg BW) was administered iv to rats 10 min before pancreatic blood flow was measured with a nonradioactive microsphere technique. In male Sprague-Dawley rats, N-arg induced a marked decrease in islet blood flow (16 +/- 4 vs. 44 +/- 8 microliters/min.g pancreas; P < 0.001) and a less pronounced decrease in whole pancreatic blood flow (0.27 +/- 0.04 vs. 0.43 +/- 0.06 ml/min.g; P < 0.05), leading to a markedly decreased fractional islet blood flow (5.5 +/- 0.9% vs. 10.3 +/- 1.3%; P < 0.02). In a second experiment, injection of D-glucose (300 mg/kg BW, iv) in male Sprague-Dawley rats induced a selective increase in islet blood flow (P < 0.05). Such an increase has previously been shown to be mediated by a vagal cholinergic mechanism. Administration of N-arg to these rats resulted in decreased pancreatic (P < 0.05), islet (P < 0.001), and fractional (P < 0.001) islet blood flow, which did not differ from those observed in normoglycemic rats after treatment with N-arg. Furthermore, we studied the mechanism behind the previously described increase in islet blood perfusion, mediated by the vagus nerve, in F1-hybrids of the GK (Goto-Kakizaki) rat, a spontaneous animal model of noninsulin-dependent diabetes mellitus. Administration of N-arg to female GK rats resulted in decreases in islet (P < 0.001), pancreatic (P < 0.01), and fractional islet blood flow (P < 0.001) to the levels observed in female Wistar rats treated in parallel. These data are consistent with the possibility that NO is an important physiological regulator of islet blood flow. Furthermore, the vagally dependent high levels of islet blood flow demonstrated in the GK rat appear to be mediated by a mechanism involving NO.

Amino Acid Oxidoreductases↗

PubMed1994

Pancreatic and islet blood flow in F1-hybrids of the non-insulin-dependent diabetic GK-Wistar rat.

Previous studies have indicated that various conditions under which an increased functional load is posed on the pancreatic islets, e.g. partial pancreatectomy and continuous glucose infusions, may influence the microcirculation of the pancreas. To investigate further the effects of elevated functional demand on the islets, the blood perfusion of the whole pancreas and the pancreatic islets was measured with a microsphere technique in an animal model presenting impaired glucose tolerance and mild hyperglycemia, namely F1-hybrids of the spontaneously non-insulin-dependent diabetic GK-Wistar rat. Normal Wistar rats served as controls. All hybrids had a pathological intraperitoneal glucose tolerance test 1 week before the blood flow measurements, which were performed in 10-12-week-old rats. Both the whole pancreatic and the islet blood flows were increased in the hybrids compared to controls. The fractional islet blood flow, i.e. the fraction of whole pancreatic blood flow diverted through the islets, also was increased in the hybrid rats (12.6 +/- 0.6% vs 9.8 +/- 0.5% in controls, p < 0.01). A bilateral abdominal vagotomy performed 30 min before the blood flow measurement markedly decreased the blood flow values of the islets and the whole pancreas in both groups of rats. After vagotomy, the islet blood flow in the hybrid rats was similar to that of the vagotomized control animals (8.2 +/- 0.8 and 7.5 +/- 1.4%, respectively). It is concluded that the increased pancreatic and islet blood perfusion observed in F1-hybrids of the GK-Wistar rat depends on a mechanism mediated by the vagus nerve.

Animals↗

PubMed1994

Pancreatic islet blood flow in the rat after administration of islet amyloid polypeptide or calcitonin gene-related peptide.

Anesthetized male Sprague-Dawley rats (350-400 g) were injected intravenously with either 0.1, 1, 15, or 25 nmol rat islet amyloid polypeptide (IAPP), 65 or 650 pmol rat calcitonin gene-related peptide (CGRP), or saline alone. IAPP at the two highest doses decreased the mean arterial blood pressure (BP), increased blood glucose concentrations, and decreased serum insulin concentrations. CGRP at both doses decreased the BP but did not affect the blood glucose concentrations. The blood flow to the whole pancreas, pancreatic islets, adrenal glands, colon, duodenum, liver, and kidney was measured with a microsphere technique 30 min after administration of IAPP and 3 min after injection of CGRP. The two higher doses of IAPP (15 and 25 nmol) markedly reduced the whole pancreatic blood flow, whereas the islet blood flow remained unaffected. This resulted in an increase in the fraction of whole pancreatic blood flow diverted through the islets from approximately 10 to 17%. No blood flow changes in the pancreas or the islets were observed when 0.1 or 1 nmol IAPP was injected. CGRP at both doses caused a decrease in both whole pancreatic and islet blood flow. No changes in fractional islet blood flow were observed, despite similar effects on mean arterial BP as observed after IAPP injections. Neither adrenal, duodenal, colonic, hepatic, skeletal muscle, nor renal blood flow were significantly affected by any of the concentrations of IAPP used, whereas 650 pmol CGRP decreased both duodenal and colonic blood flow. We conclude that IAPP and CGRP have different effects on pancreatic islet blood flow and that IAPP may be of importance for islet blood flow regulation.

Amyloid↗

PubMed1993

Early electrocardiographic changes in acute myocardial infarction treated by streptokinase or alteplase: a randomized study with dynamic, multi-lead, electrocardiographic monitoring.

Patients with a patent coronary artery after reperfusion therapy show an increased rate of evolution of QRS changes and of resolution of S-T changes as compared to patients with a persistent occlusion. Dynamic vectorcardiography permits multi-lead monitoring of changes in QRS complex and S-T segment over time. We monitored 150 patients randomized to alteplase or streptokinase for 24 h after admission. Alteplase was associated with significantly more rapid evolution of electrocardiographic changes but also with an increased occurrence of recurrent S-T changes. This may indicate a higher rate of early reperfusion with alteplase but due to recurrent ischemia, an electrocardiographic catch-up is seen with similar extent of myocardial damage observed after 24 h of monitoring.

Aged↗

PubMed1992

Glucose metabolism in embryos of normal and diabetic rats during organogenesis.

To investigate whether malformations in the offspring of diabetic rats are related to a disturbed embryonic glucose metabolism, lactate production, lactate content and glucose oxidation in embryos of normal and manifestly diabetic rats were measured in vitro during the period of organogenesis. The embryonic production and content of lactate decreased by 90% between gestational days 10 and 11. On both gestational days the embryos of diabetic rats showed increased lactate production and content compared to the embryos of normal rats. The embryonic oxidation of glucose decreased slightly from gestational day 10 to day 11, and the embryos of diabetic rats exhibited a lower glucose oxidation rate than those of normal rats on both days. The lactate production and content in the embryos increased with increasing concentrations of glucose in the incubation medium, whereas the oxidation of glucose was unaffected by the glucose concentration. The results suggest that the embryonic metabolism of glucose is only marginally affected by changes in the availability of glucose. The lactate production rate was higher and the glucose oxidation rate lower in the embryos of diabetic than in those of normal rats, even when the values for these metabolic variables were normalized to the embryonic DNA content. Thus, a causative role for a disturbance of the glucose metabolism in diabetes-induced embryonic dysmorphogenesis could be envisaged.

Animals↗

PubMed1988

The volume and area of the capillaries in the endocrine and exocrine pancreas of the rat.

The capillary volumes in the endocrine and exocrine parenchyma of the pancreas were compared with a point-sampling technique. The islets were found to have a capillary volume of approximately 3.5%, while the value for the exocrine pancreas was significantly (P less than 0.001) lower at 2%. When the capillary wall area was measured, however, both types of parenchyma had a similar value of approximately 20 mm2/mm3 tissue. The reason for the discrepancy between these parameters is probably the lack of lymphatic capillaries, with their relatively small lumen in the islets.

Alkaline Phosphatase↗