scholarly journals Unaltered pancreatic islet blood perfusion in islet amyloid polypeptide-deficient mice

2002 ◽  
pp. 107-112 ◽  
Author(s):  
PO Carlsson ◽  
E Karlsson ◽  
H Mulder ◽  
S Gebre-Medhin

OBJECTIVE: Several biological activities have been ascribed to islet amyloid polypeptide (IAPP). However, their physiological relevance remains unclear. Previous studies in rats with exogenous administration of IAPP suggest that the peptide may increase splanchnic vascular resistance and redistribute the blood flow within the pancreas to the islets. In this study, the use of IAPP-deficient mice allowed us to evaluate possible effects of the lack of IAPP on splanchnic blood perfusion and we could thereby circumvent the potentially pharmacological actions of exogenously administered IAPP. DESIGN: Regional splanchnic blood flow was measured after exogenous administration of IAPP and in IAPP-deficient mice. METHODS: Blood flow values were determined using a non-radioactive microsphere technique in anesthetized animals. RESULTS: No differences in whole pancreatic blood flow or islet blood flow could be detected in IAPP-deficient mice when compared with control mice; neither did IAPP deficiency affect the glucose-induced increase in islet blood flow. Duodenal, ileal and colonic blood flows were similar in IAPP-deficient and control mice. Exogenous administration of IAPP selectively increased islet blood flow in wild-type control mice. CONCLUSIONS: The present findings in the IAPP-deficient mice suggest that the vascular effects seen in the islets after exogenous administration of IAPP to normal mice reflect pharmacological, rather than physiological effects of the peptide. We conclude that the lack of endogenous IAPP within the splanchnic vascular system does not alter the blood perfusion of pancreatic islets or other splanchnic organs.

1992 ◽  
Vol 263 (1) ◽  
pp. E57-E63 ◽  
Author(s):  
L. Jansson ◽  
S. Sandler

It has recently been shown that selective B-cell toxins alloxan and streptozotocin (STZ) possess marked effects also on the vascular system. To evaluate to what extent changes in blood perfusion of islets induced by alloxan or STZ could be of importance for diabetogenic action of these compounds, we first investigated acute effects of alloxan (75 mg/kg body wt iv) and STZ (40 mg/kg body wt iv) on both whole pancreatic blood flow (PBF) and islet blood flow (IBF) in adult rats. Alloxan caused a marked increase in IBF, which was most pronounced 3 min after administration and remained for 30 min. PBF, however, was decreased 3 min after alloxan administration but was similar to that of control animals from 10 min and onward. These two opposite effects on IBF and PBF caused the fraction of whole PBF diverted through islets to increase from approximately 10 to 50%. Pretreatment with glucose (2 g/kg body wt iv), indomethacin (3.5 mg/kg body wt iv), dimethyl sulfoxide (10 ml/kg body wt ip of a 33% solution), superoxide dismutase (SOD, 1,000 kU/kg body wt iv), NG-methyl-L-arginine (30 mg/kg body wt iv), theophylline (7 mg/kg body wt iv), or terbutaline (1 mg/kg body wt iv) failed to affect stimulation of IBF by alloxan observed at 3 min. SOD was found to exert a marked stimulation of IBF both when given alone and together with alloxan. Alloxan increased IBF and decreased PBF also in a syngeneic pancreaticoduodenal graft in rats but did not affect flow distribution in a perfused pancreas-duodenum preparation.(ABSTRACT TRUNCATED AT 250 WORDS)


2007 ◽  
Vol 292 (6) ◽  
pp. E1616-E1623 ◽  
Author(s):  
En Yin Lai ◽  
A. Erik G. Persson ◽  
Birgitta Bodin ◽  
Örjan Källskog ◽  
Arne Andersson ◽  
...  

Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor, which also stimulates insulin release. The aim of the present study was to evaluate whether exogenously administered ET-1 affected pancreatic islet blood flow in vivo in rats and the islet arteriolar reactivity in vitro in mice. Furthermore, we aimed to determine the ET-receptor subtype that was involved in such responses. When applying a microsphere technique for measurements of islet blood perfusion in vivo, we found that ET-1 (5 nmol/kg) consistently and markedly decreased total pancreatic and especially islet blood flow, despite having only minor effects on blood pressure. Neither endothelin A (ETA) receptor (BQ-123) nor endothelin-B (ETB) receptor (BQ-788) antagonists, alone or in combination, could prevent this reduction in blood flow. To avoid confounding interactions in vivo, we also examined the arteriolar vascular reactivity in isolated, perfused mouse islets. In the latter preparation, we demonstrated a dose-dependent constriction in response to ET-1. Administration of BQ-123 prevented this, whereas BQ-788 induced a right shift in the response. In conclusion, the pancreatic islet vasculature is highly sensitive to exogenous ET-1, which mediates its effect mainly through ETA receptors.


2005 ◽  
Vol 153 (2) ◽  
pp. 345-351 ◽  
Author(s):  
Leif Jansson ◽  
Birgitta Bodin ◽  
Örjan Källskog ◽  
Arne Andersson

Objectives: The aim of this study was to evaluate islet blood-flow changes during stimulated growth of the islet organ without any associated functional impairment of islet function. Design: A duct ligation encompassing the distal two-thirds of the pancreas was performed in adult, male Sprague–Dawley rats. Methods: Pancreatic islet blood flow was measured in duct-ligated and sham-operated rats 1, 2 or 4 weeks after surgery. In some animals studied 4 weeks after surgery, islet blood flow was also measured also during hyperglycaemic conditions. Results: A marked atrophy of the exocrine pancreas was seen in all duct-ligated rats. Blood glucose and serum insulin concentrations were normal. An increased islet mass was only seen 4 weeks after surgery. No differences in islet blood perfusion were noted at any time point after duct ligation. In both sham-operated and duct-ligated rats islet blood flow was increased during hyperglycaemia; the response was, however, slightly more pronounced in the duct-ligated part of the gland. Conclusions: Normal, physiological islet growth does not cause any major changes in the islet blood perfusion or its regulation. This is in contrast to findings during increased functional demands on the islets or during deteriorated islet function, when increased islet blood flow is consistently seen.


1996 ◽  
Vol 151 (3) ◽  
pp. 507-511 ◽  
Author(s):  
A M Svensson ◽  
C Hellerström ◽  
L Jansson

Abstract 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. Journal of Endocrinology (1996) 151, 507–511


1981 ◽  
Vol 241 (1) ◽  
pp. R36-R43 ◽  
Author(s):  
R. B. Page ◽  
D. J. Funsch ◽  
R. W. Brennan ◽  
M. J. Hernandez

Regional neurohypophyseal and cerebral blood flows were measured by the radiolabeled microsphere technique in 30 adult sheep under light barbiturate anesthesia. Regional blood flows were determined under basal conditions. The responses of regional blood flow to alterations in arterial PCO2 and to changes in arterial blood pressure wee also determined. In addition, the relationship between regional neurohypophyseal blood flow and neurosecretory activity as judged by plasma arginine vasopressin levels was assessed. Under basal conditions median eminence blood flow averaged 461 ml.100 g-1.min-1 and did not significantly differ from neural lobe blood flow (436 ml.100 g-1.min-1). Blood flow in the neurohypophysis was about 8 times cortical and 16 times white matter blood flow in these animals. Median eminence and neural lobe blood flow proportionately increased far less than regional cortical or white matter blood flow under conditions of hypercarbia. With alteration of arterial blood pressure, regional neurohypophyseal blood flow remained constant beyond the limits of cerebral autoregulation. The neurohypophysis demonstrates a degree of blood flow homeostasis that exceeds that of any other brain area studied. Although the neurohypophysis is a diverticulum of the brain, its vascular system forms a unique functional as well as a unique anatomic unit.


2000 ◽  
Vol 279 (5) ◽  
pp. E1139-E1144 ◽  
Author(s):  
Annika M. Svensson ◽  
Claes-Göran Östenson ◽  
Leif Jansson

The present study aimed to compare longitudinal variations in islet blood perfusion in rats with different degrees of impairment of glucose metabolism. For this purpose, mildly diabetic Goto-Kakizaki (GK) rats, glucose intolerant F1 hybrids of GK and Wistar (W) rats (H), and control W rats were examined at 5 wk, 12 wk, or 1 yr of age, using the microsphere technique for blood flow measurements. W rats showed progressively increasing islet blood flow (IBF) throughout the experiment. Both GK and H rats demonstrated increasing IBF between 5 and 12 wk. However, H rats showed no further increment in IBF at 1 yr, whereas GK rats displayed a pronounced decrease in IBF between 12 wk and 1 yr of age. The augmented IBF seen in older W rats may constitute an adaptation to the increasing demand for insulin secretion in aging rats. The inability to adapt to the increased demand for insulin secretion by upregulation of islet blood flow could contribute to the progressive deterioration of glucose metabolism seen in the aging GK rat.


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