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Källskog, Örjan
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Publications (10 of 15) Show all publications
Broman, L. M., Carlström, M., Källskog, Ö. & Wolgast, M. (2017). Effect of nitric oxide on renal autoregulation during hypothermia in the rat.. Pflügers Archiv: European Journal of Physiology, 469(5-6), 669-680
Open this publication in new window or tab >>Effect of nitric oxide on renal autoregulation during hypothermia in the rat.
2017 (English)In: Pflügers Archiv: European Journal of Physiology, ISSN 0031-6768, E-ISSN 1432-2013, Vol. 469, no 5-6, p. 669-680Article in journal (Refereed) Published
Abstract [en]

Hypothermia-induced reduction of metabolic rate is accompanied by depression of both glomerular perfusion and filtration. The present study investigated whether these changes are linked to changes in renal autoregulation and nitric oxide (NO) signalling. During hypothermia, renal blood flow (RBF) and glomerular filtration rate (GFR) were reduced and urine production was increased, and this was linked with reduced plasma cGMP levels and increased renal vascular resistance. Although stimulation of NO production decreased vascular resistance, blood pressure and urine flow, intravenous infusion of the NO precursor L-arginine or the NO donor sodium nitroprusside did not alter RBF or GFR. In contrast, inhibition of NO synthesis by N(w)-nitro-L-arginine led to a further decline in both parameters. Functional renal autoregulation was apparent at both temperatures. Below the autoregulatory range, RBF in both cases increased in proportion to the perfusion ±pressure, although, the slope of the first ascending limb of the pressure-flow relationship was lower during hypothermia. The main difference was rather that the curves obtained during hypothermia levelled off already at a RBF of 3.9 ± 0.3 mL/min then remained stable throughout the autoregulatory pressure range, compared to 7.6 ± 0.3 mL/min during normothermia. This was found to be due to a threefold increase in, primarily, the afferent arteriolar resistance from 2.6 to 7.5 mmHg min mL(-1). Infusion of sodium nitroprusside did not significantly affect RBF during hypothermia, although a small increase at pressures below the autoregulatory range was observed. In conclusion, cold-induced rise in renal vascular resistance results from afferent arteriolar vasoconstriction by the autoregulatory mechanism, setting RBF and GFR in proportion to the metabolic rate, which cannot be explained by reduced NO production alone.

Keywords
Autoregulation, GFR, Hypothermia, Nitric oxide, Renal blood flow, Vascular resistance
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-317887 (URN)10.1007/s00424-017-1967-1 (DOI)000401865900008 ()28315005 (PubMedID)
Funder
Swedish Research Council, K97-04X-11557-02B, 2016-01381Swedish Heart Lung Foundation, 20140448
Available from: 2017-03-21 Created: 2017-03-21 Last updated: 2017-08-07Bibliographically approved
Jansson, L., Barbu, A., Bodin, B., Drott, C. J., Espes, D., Gao, X., . . . Carlsson, P.-O. (2016). Pancreatic islet blood flow and its measurement. Upsala Journal of Medical Sciences, 121(2), 81-95
Open this publication in new window or tab >>Pancreatic islet blood flow and its measurement
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2016 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 2, p. 81-95Article, review/survey (Refereed) Published
Abstract [en]

Pancreatic islets are richly vascularized, and islet blood vessels are uniquely adapted to maintain and support the internal milieu of the islets favoring normal endocrine function. Islet blood flow is normally very high compared with that to the exocrine pancreas and is autonomously regulated through complex interactions between the nervous system, metabolites from insulin secreting beta-cells, endothelium derived mediators, and hormones. The islet blood flow is normally coupled to the needs for insulin release and is usually disturbed during glucose intolerance and overt diabetes. The present review provides a brief background on islet vascular function and especially focuses on available techniques to measure islet blood perfusion. The gold standard for islet blood flow measurements in experimental animals is the microsphere technique, and its advantages and disadvantages will be discussed. In humans there are still no methods to measure islet blood flow selectively, but new developments in radiological techniques hold great hopes for the future.

Keywords
Blood flow measurements, islet blood flow, microspheres, pancreatic islets
National Category
General Practice
Identifiers
urn:nbn:se:uu:diva-299775 (URN)10.3109/03009734.2016.1164769 (DOI)000376695600004 ()27124642 (PubMedID)
Funder
Swedish Research CouncilSwedish Diabetes AssociationSwedish Childhood Cancer FoundationNovo Nordisk
Available from: 2016-07-27 Created: 2016-07-27 Last updated: 2018-01-10Bibliographically approved
Lai, E., Pettersson, U., Verdugo, A. D., Carlsson, P.-O., Bodin, B., Källskog, Ö., . . . Jansson, L. (2014). Blood lipids affect rat islet blood flow regulation through beta(3)-adrenoceptors. American Journal of Physiology. Endocrinology and Metabolism, 307(8), E653-E663
Open this publication in new window or tab >>Blood lipids affect rat islet blood flow regulation through beta(3)-adrenoceptors
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2014 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 307, no 8, p. E653-E663Article in journal (Refereed) Published
Abstract [en]

Pancreatic islet blood perfusion varies according to the needs for insulin secretion. We examined the effects of blood lipids on pancreatic islet blood flow in anesthetized rats. Acute administration of Intralipid to anesthetized rats increased both triglycerides and free fatty acids, associated with a simultaneous increase in total pancreatic and islet blood flow. A preceding abdominal vagotomy markedly potentiated this and led acutely to a 10-fold increase in islet blood flow associated with a similar increase in serum insulin concentrations. The islet blood flow and serum insulin response could be largely prevented by pretreatment with propranolol and the selective beta(3)-adrenergic inhibitor SR-59230A. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester prevented the blood flow increase but was less effective in reducing serum insulin. Increased islet blood flow after Intralipid administration was also seen in islet and whole pancreas transplanted rats, i.e., models with different degrees of chronic islet denervation, but the effect was not as pronounced. In isolated vascularly perfused single islets Intralipid dilated islet arterioles, but this was not affected by SR-59230A. Both the sympathetic and parasympathetic nervous system are important for the coordination of islet blood flow and insulin release during hyperlipidemia, with a previously unknown role for beta(3)-adrenoceptors.

Keywords
pancreatic islets
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-236532 (URN)10.1152/ajpendo.00680.2013 (DOI)000343223700004 ()25139049 (PubMedID)
Available from: 2014-11-26 Created: 2014-11-19 Last updated: 2017-12-05Bibliographically approved
Jansson, L., Kampf, C. & Källskog, Ö. (2013). Functional stimulation of graft nerves has minor effects on insulin release from transplanted rat pancreatic islets. Upsala Journal of Medical Sciences, 118(4), 209-216
Open this publication in new window or tab >>Functional stimulation of graft nerves has minor effects on insulin release from transplanted rat pancreatic islets
2013 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 4, p. 209-216Article in journal (Refereed) Published
Abstract [en]

Introduction. Morphological evidence for reinnervation of pancreatic islet grafts is plentiful. However, to what extent intra-graft nerves influence the endocrine functions of the islet transplant is largely unknown. We therefore aimed to directly stimulate nerves leading to islet grafts with electrodes and measure insulin secretion in response to this.

Methods. We implanted syngeneic islets under the renal capsule of rats, and examined them 1 or 7-9 months later. In anesthetized rats blood samples were collected from the renal vein and femoral artery, respectively, during electrode stimulation of the nerves leading to the islet grafts. Results. As expected, nerve stimulation decreased renal blood flow. However, serum insulin concentrations in samples derived from the renal vein or femoral artery changed in concert with one another, both during normoglycemia and acute hyperglycemia.

Conclusion. Reinnervation which occurs after islet transplantation under the renal capsule has minor effects on graft endocrine function.

Keywords
Insulin release, islet transplantation, pancreatic islets, reinnervation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-210562 (URN)10.3109/03009734.2013.818601 (DOI)000325527300001 ()
Available from: 2013-11-13 Created: 2013-11-11 Last updated: 2017-12-06Bibliographically approved
Barbu, A., Johansson, Å., Bodin, B., Källskog, Ö., Carlsson, P.-O., Sandberg, M., . . . Jansson, L. (2012). Blood flow in endogenous and transplanted pancreatic islets in anesthetized rats: Effects of lactate and pyruvate. Pancreas, 41(8), 1263-1271
Open this publication in new window or tab >>Blood flow in endogenous and transplanted pancreatic islets in anesthetized rats: Effects of lactate and pyruvate
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2012 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 41, no 8, p. 1263-1271Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The objective of this study was to evaluate the effects of exogenously administered lactate and pyruvate on blood perfusion in endogenous and transplanted islets. METHODS: Anesthetized Wistar-Furth rats were given lactate or pyruvate intravenously, and regional blood perfusion was studied 3 or 30 minutes later with a microsphere technique. Separate rats received a 30-minute infusion of pyruvate or lactate into the portal vein before blood flow measurements. We also administered these substances to islet-implanted rats 4 weeks after transplantation and measured graft blood flow with laser Doppler flowmetry. The expression of monocarboxylate transporter 1 and lactate dehydrogenase A was analyzed. RESULTS: The expression of monocarboxylate transporter 1 and lactate dehydrogenase A was markedly up-regulated in transplanted as compared with endogenous islets. Administration of pyruvate, but not lactate, increased mesenteric blood flow after 3 minutes. Pyruvate decreased mesenteric blood flow after 30 minutes, whereas lactate decreased only islet blood flow. These responses were absent in transplanted animals. A continuous intraportal infusion of lactate or pyruvate increased selectively islet blood flow but did not affect blood perfusion of transplanted islets. CONCLUSIONS: Lactate and pyruvate affect islet blood flow through effects mediated by interactions between the liver and the nervous system. Such a response can help adjust the release of islet hormones during excess substrate concentrations.

Keywords
blood flow, lactate, pancreatic islets, pyruvate
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-186004 (URN)10.1097/MPA.0b013e31824bd97c (DOI)000310360500015 ()
Available from: 2012-11-28 Created: 2012-11-27 Last updated: 2017-12-07Bibliographically approved
Källskog, Ö. & Jansson, L. (2011). Autoregulation of Islet Graft Blood Flow Follows the Implantation. Journal of Surgical Research, 171(2), 865-870
Open this publication in new window or tab >>Autoregulation of Islet Graft Blood Flow Follows the Implantation
2011 (English)In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 171, no 2, p. 865-870Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Transplantation of pancreatic islets necessitates a revascularization, which is associated with a generalized graft vascular dysfunction, manifested, e.g., as a capillary hypertension, a decreased graft blood perfusion and graft hypoxia. Some of these changes can be due to impaired autoregulation of the newly formed vasculature in the islet grafts, and the aim of the present study was to further examine if this was the case.

MATERIALS AND METHODS: We implanted 250 syngeneic islets under the renal capsule of rats and studied them 1 or 12-13 mo later. The blood perfusion of the whole kidney, renal cortex, and islet grafts were recorded in anesthetized animals with an ultrasound probe or laser-Doppler probes, respectively. The blood pressure in the kidneys was then gradually decreased by an adjustable clamp, during simultaneous measurement of blood flow values. RESULTS: The whole kidney, renal cortex, and islet grafts regulated their blood flow in concert with one another down to pressures of approximately 60 mmHg both 1 and 12-13 mo after implantation. However, the variability was greater at 1 mo.

CONCLUSION: Islets transplanted under the renal capsule show similar autoregulatory properties with the kidney. It may be that the autoregulatory capacity of the renal interlobular arteries provides the underlying mechanism. This may be of importance for the good long-term survival of transplanted islets at this implantation site in experimental studies.

Keywords
autoregulation; blood flow; engraftment; islet transplantation; islet vasculature
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-141972 (URN)10.1016/j.jss.2010.07.061 (DOI)000296957900086 ()20888593 (PubMedID)
Available from: 2011-01-13 Created: 2011-01-13 Last updated: 2018-01-12Bibliographically approved
Jansson, L., Andersson, A., Bodin, B. & Källskog, Ö. (2007). Pancreatic islet blood flow during euglycaemic, hyperinsulinaemic clamp in anaesthetized rats. Acta Physiologica, 189(4), 319-324
Open this publication in new window or tab >>Pancreatic islet blood flow during euglycaemic, hyperinsulinaemic clamp in anaesthetized rats
2007 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 189, no 4, p. 319-324Article in journal (Refereed) Published
Abstract [en]

Aims: Previous studies have demonstrated that pancreatic islet blood flow is crucially dependent on blood glucose concentration. Thus, hyperglycaemia increases and hypoglycaemia decreases islet blood perfusion, by a combination of nervous and metabolic signals. The aim of the present study was to evaluate if hyperinsulinaemia, without associated hypoglycaemia, affects islet blood flow.

Methods: Thiobutabarbital-anaesthetized Wistar–Furth rats were subjected to an euglycaemic, hyperinsulinaemic clamp, that is they were infused for 60 min with either saline, insulin (18 mU kg−1 min−1), glucose (27 mg kg−1 min−1) or both glucose and insulin. This was followed by islet blood flow measurements with a microsphere technique.

Results: Animals receiving only glucose doubled their blood glucose and serum insulin concentrations, whereas rats receiving only insulin had blood glucose concentrations <2 mmol L−1 and a 10-fold increase in serum insulin concentrations. Animals given simultaneous glucose and insulin had normal blood glucose concentrations but a 10-fold increase in serum insulin concentrations. Total pancreatic blood flow was unaffected in all animals. Islet blood flow was increased in hyperglycaemic and decreased in hypoglycaemic rats compared with control rats. Islet blood flow did not differ between clamped and control rats.

Conclusions: Serum insulin concentration per se does not affect islet blood flow, whereas the ambient blood glucose concentration is of major importance in this context.

Keywords
euglycaemic hyperinsulinaemic clamp, hyperglycaemia, hypoglycaemia, Islet blood flow
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-11909 (URN)10.1111/j.1748-1716.2006.01666.x (DOI)000244887000002 ()
Available from: 2007-11-06 Created: 2007-11-06 Last updated: 2017-12-11Bibliographically approved
Fang, Z., Duthoit, N., Wicher, G., Källskog, Ö., Ambartsumian, N., Lukanidin, E., . . . Kozlova, E. N. (2006). Intracellular calcium-binding protein S100A4 influences injury-induced migration of white matter astrocytes.. Acta Neuropathol (Berl), 111(3), 213-9
Open this publication in new window or tab >>Intracellular calcium-binding protein S100A4 influences injury-induced migration of white matter astrocytes.
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2006 (English)In: Acta Neuropathol (Berl), ISSN 0001-6322, Vol. 111, no 3, p. 213-9Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-79818 (URN)16463066 (PubMedID)
Available from: 2007-01-22 Created: 2007-01-22 Last updated: 2011-01-11
Källskog, Ö., Kampf, C., Andersson, A., Carlsson, P.-O., Hansell, P., Johansson, M. & Jansson, L. (2006). Lymphatic vessels in pancreatic islets implanted under the renal capsule of rats.. Am J Transplant, 6(4), 680-6
Open this publication in new window or tab >>Lymphatic vessels in pancreatic islets implanted under the renal capsule of rats.
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2006 (English)In: Am J Transplant, ISSN 1600-6135, Vol. 6, no 4, p. 680-6Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-80251 (URN)16539624 (PubMedID)
Available from: 2007-11-07 Created: 2007-11-07 Last updated: 2011-01-11
Johansson, M., Carlsson, P.-O., Bodin, B., Andersson, A., Källskog, Ö. & Jansson, L. (2005). Acute effects of a 50% partial pancreatectomy on total pancreatic and islet blood flow in rats.. Pancreas, 30(1), 71-5
Open this publication in new window or tab >>Acute effects of a 50% partial pancreatectomy on total pancreatic and islet blood flow in rats.
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2005 (English)In: Pancreas, ISSN 1536-4828, Vol. 30, no 1, p. 71-5Article in journal (Refereed) Published
Keywords
Anesthesia, Animals, Blood Glucose, Insulin/blood, Islets of Langerhans/*blood supply/metabolism/*surgery, Male, Microspheres, Pancreas; Exocrine/*blood supply/*surgery, Pancreatectomy/methods, Rats, Rats; Sprague-Dawley, Regional Blood Flow, Research Support; Non-U.S. Gov't
Identifiers
urn:nbn:se:uu:diva-79737 (URN)15632702 (PubMedID)
Available from: 2006-12-11 Created: 2006-12-11 Last updated: 2011-01-11
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