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Reversal of high pancreatic islet and white adipose tissue blood flow in type 2 diabetic GK rats by administration of the beta(3)-adrenoceptor inhibitor SR-59230A
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
2009 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 297, no 2, E490-E494 p.Article in journal (Refereed) Published
Abstract [en]

Pettersson US, Henriksnas J, Jansson L. Reversal of high pancreatic islet and white adipose tissue blood flow in type 2 diabetic GK rats by administration of the beta(3)-adrenoceptor inhibitor SR-59230A. Am J Physiol Endocrinol Metab 297: E490-E494, 2009. First published June 2, 2009; doi: 10.1152/ajpendo.00140.2009.-Previous studies have shown that the Goto-Kakizaki (GK) rat, a nonobese type 2 diabetes model, has an increased white adipose tissue (WAT) and islet blood flow when compared with control rats. The aim of the study was to examine if these increased blood flow values in GK rats could be affected by the beta(3)-adrenoceptor antagonist SR-59230A. We measured organ blood flow with a microsphere technique 10 min after administration of SR-59230A (1 mg/kg body wt), or the corresponding volume of 0.9% NaCl solution (1 ml/kg body wt) in rats anaesthetized with thiobutabarbital. The GK rat had an increased blood flow in all intra-abdominal adipose tissue depots except for the sternal fat pad compared with Wistar-Furth (WF) rats. However, no differences were seen in the blood perfusion of subcutaneous white or brown adipose tissue. The blood flow was also increased in both the pancreas and in the islets in the GK rat compared with WF rats. SR-59230A treatment affected neither WAT nor pancreatic blood flow in WF rats. In GK rats, on the other hand, SR-59230A decreased both WAT and islet blood flow values to values similar to those seen in control WF rats. The whole pancreatic blood flow was not affected by SR-59230A administration in GK rats. Interestingly, the brown adipose tissue blood flow in GK rats increased after SR-59230A administration. These results suggest that beta(3)-adrenoceptors are involved in regulation of blood flow both in islet and in adipose tissue.

Place, publisher, year, edition, pages
2009. Vol. 297, no 2, E490-E494 p.
Keyword [en]
microsphere, in vivo, Goto-Kakizaki
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-128366DOI: 10.1152/ajpendo.00140.2009ISI: 000268252700024OAI: oai:DiVA.org:uu-128366DiVA: diva2:331405
Available from: 2010-07-22 Created: 2010-07-20 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Blood Flow Regulation and Inflammatory Response in Experimental Models of Diabetes
Open this publication in new window or tab >>Blood Flow Regulation and Inflammatory Response in Experimental Models of Diabetes
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Type 2 diabetes is caused by defect pancreatic islet β-cells together with peripheral insulin resistance. The disease is often accompanied by obesity with associated low-grade visceral adipose tissue inflammation, which contributes to insulin resistance. As a consequence of, and a possible compensation for the increased insulin demand, blood flow to the pancreatic islets is increased in animal models of diabetes. This increased blood perfusion might with time affect the vascular network as well as β-cells within the islets.

This thesis investigates the role of changes of blood perfusion in pancreatic islets and adipose tissues, as well as the recruitment to and composition of leukocyte subpopulations in insulin-sensitive tissues in experimental models of diabetes.

Blood flow measurements in islets and adipose tissues of rats and mice were performed using the microsphere technique, while leukocyte recruitment was studied in the mouse cremaster muscle using intravital microscopy. Increased islet blood flow was observed in the GK rat model of type 2 diabetes, which was decreased by acute as well as continuous 2-week inhibition of β3-adrenoceptors without affecting plasma insulin concentrations. Increased inflammatory leukocyte recruitment was observed in both alloxan-induced and high-fat diet-induced diabetes. However, an impaired bacterial clearance was observed in diabetic mice, which was due to impaired phagocytosis. A gender difference was detected in mice fed a high-fat diet, since obese female mice did not show increased levels of pro-inflammatory circulatory markers or inflammatory leukocytes in the adipose tissue. The main effector cell in the adipose tissue inflammation in high-fat-fed male mice seemed to be the pro-inflammatory macrophage. The Treg population in adipose tissue was increased in female mice, but remained unchanged in male mice on high-fat diet.

In conclusion, increased islet blood flow in type 2 diabetes could be reversed by β3-adrenoceptor inhibition, which may maintain islet function. The diabetes-associated hyperglycemia activated leukocytes but impaired their phagocytic ability. High-fat-fed female mice showed less peripheral inflammation due to a smaller number of recruited inflammatory macrophages and a high-fat diet-induced Treg population in intra-abdominal adipose tissues.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 60 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 733
Keyword
Islets, beta-cells, pancreas, inflammation, obesity, adipose tissue, rats, mice, leukocytes, beta3-adrenoceptors
National Category
Physiology Cell and Molecular Biology
Research subject
Medical Cell Biology
Identifiers
urn:nbn:se:uu:diva-161807 (URN)978-91-554-8247-3 (ISBN)
Public defence
2012-02-10, B41, BMC, Husargatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2012-01-20 Created: 2011-11-17 Last updated: 2012-01-24Bibliographically approved

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