Carbon monoxide and pancreatic islet blood flow in the rat: Inhibition of haem oxygenase does not affect islet blood perfusion

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.

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Duct ligation and pancreatic islet blood flow in rats: physiological growth of islets does not affect islet blood perfusion

Acta Endocrinologica ◽

10.1530/eje.1.01966 ◽

2005 ◽

Vol 153 (2) ◽

pp. 345-351 ◽

Cited By ~ 6

Author(s):

Leif Jansson ◽

Birgitta Bodin ◽

Örjan Källskog ◽

Arne Andersson

Keyword(s):

Blood Flow ◽

Pancreatic Islet ◽

Serum Insulin ◽

Blood Perfusion ◽

Islet Function ◽

Sprague Dawley ◽

Islet Mass ◽

Islet Blood Flow ◽

Sprague Dawley Rats ◽

Duct Ligation

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.

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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

Journal of Endocrinology ◽

10.1677/joe.0.1510507 ◽

1996 ◽

Vol 151 (3) ◽

pp. 507-511 ◽

Cited By ~ 17

Author(s):

A M Svensson ◽

C Hellerström ◽

L Jansson

Keyword(s):

Blood Flow ◽

Body Weight ◽

Glucose Tolerance ◽

Pancreatic Islet ◽

Wistar Rats ◽

Blood Perfusion ◽

Cafeteria Diet ◽

Standard Diet ◽

Diet Induced Obesity ◽

Islet Blood Flow

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

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Effects of glucagon-like peptide-1-(7–36)-amide on pancreatic islet and intestinal blood perfusion in Wistar rats and diabetic GK rats

Clinical Science ◽

10.1042/cs20060272 ◽

2007 ◽

Vol 112 (6) ◽

pp. 345-351 ◽

Cited By ~ 20

Author(s):

Annika M. Svensson ◽

Claes-Göran Östenson ◽

Suad Efendic ◽

Leif Jansson

Keyword(s):

Blood Flow ◽

Pancreatic Islet ◽

Wistar Rats ◽

Blood Perfusion ◽

Glucose Administration ◽

Gk Rats ◽

Islet Blood Flow ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Pre Treatment

The aim of the present study was to evaluate the effects of GLP-1 [glucagon-like peptide-1-(7–36)-amide] on total pancreatic, islet and intestinal blood perfusion in spontaneously hyperglycaemic GK rats and normal Wistar rats using a microsphere technique. GK rats had hyperglycaemia and increased pancreatic and islet blood flow. Blood glucose concentrations were not affected when measured shortly (8 min) after GLP-1 administration in either GK or Wistar rats. GLP-1 had no effects on baseline pancreatic or islet blood flow in Wistar rats, but did prevent the blood flow increase normally seen following glucose administration to these animals. In GK rats, administration of GLP-1 decreased both pancreatic and islet blood flow. Glucose administration to the GK rats decreased pancreatic and islet blood flow. This decrease was not affected by pre-treatment with GLP-1. We conclude that administration of GLP-1 leads to a decrease in the augmented blood flow seen in islets of diabetic GK rats. The GLP-1-induced action on islet blood perfusion may modulate output of islet hormones and contribute to the antidiabetogenic effects of the drug in Type 2 diabetes (non-insulin-dependent diabetes).

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Age-Dependent changes of pancreatic islet blood flow in the rat

International Journal of Gastrointestinal Cancer ◽

10.1007/bf02924416 ◽

1989 ◽

Vol 5 (2) ◽

Author(s):

Leif Jansson ◽

Ingemar Swenne

Keyword(s):

Blood Flow ◽

Pancreatic Islet ◽

Islet Blood Flow ◽

Age Dependent

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A specific β3-adrenoceptor agonist induces increased pancreatic islet blood flow and insulin secretion in rats

European Journal of Pharmacology ◽

10.1016/0014-2999(95)00802-0 ◽

1996 ◽

Vol 298 (3) ◽

pp. 287-292 ◽

Cited By ~ 36

Author(s):

Nadia Atef ◽

Max Lafontan ◽

Alexandre Double ◽

Christophe Hélary ◽

Alain Ktorza ◽

...

Keyword(s):

Blood Flow ◽

Insulin Secretion ◽

Pancreatic Islet ◽

Islet Blood Flow ◽

Adrenoceptor Agonist

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Increased islet blood flow in obese rats: role of the autonomic nervous system

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.262.5.e736 ◽

1992 ◽

Vol 262 (5) ◽

pp. E736-E740 ◽

Cited By ~ 8

Author(s):

N. Atef ◽

A. Ktorza ◽

L. Picon ◽

L. Penicaud

Keyword(s):

Blood Flow ◽

Insulin Secretion ◽

Pancreatic Islet ◽

Ventromedial Hypothalamus ◽

Zucker Rats ◽

Islet Blood Flow ◽

Obese Rats ◽

Increased Sensitivity ◽

Obese Zucker Rats

Hyperinsulinemia, a main feature of both human and animal obesity, has been demonstrated to be due to both an increased sensitivity to nutrient secretagogues and an impairment of the nervous regulation of insulin secretion. Recent studies have shown that pancreatic islet blood flow increases under conditions associated with an enhanced insulin secretion. The aim of this study was to determine whether or not changes in islet blood flow are present in hyperinsulinemic obese rats. Using the nonradioactive microsphere technique, we were able to show a significantly higher islet blood flow in obese rats either of the Zucker strain or Wistar rats after lesion of the ventromedial hypothalamus than in their respective lean controls. Subdiaphragmatic vagotomy had no significant effect on basal islet blood flow of lean rats, whereas it decreased significantly that of obese Zucker rats. Conversely, clonidine, an alpha 2-adrenergic agonist, induced a higher decrease of islet blood flow in obese than in lean Zucker rats. The injection of an intravenous bolus of glucose (375 mg/kg iv) increased significantly more islet blood flow in obese than in lean Zucker rats. It is concluded that obese rats present an increased pancreatic islet blood flow, which may result, at least in part, from exaggerated parasympathetic activity and lower than normal sympathetic activity. This could participate in the hyperinsulinemia observed in these rats.

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