Alloxan, but not streptozotocin, increases blood perfusion of pancreatic islets in rats

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)

1983 ◽  
Vol 244 (6) ◽  
pp. G660-G667 ◽  
Author(s):  
T. Homma ◽  
K. U. Malik

We investigated the effect of secretin and caerulein on pancreatic circulation and exocrine secretion and its relation to prostaglandin (PG) synthesis by studying the effect of these peptides on the pancreatic blood flow and the flow rate of pancreatic exocrine secretion in the isolated blood-perfused pancreas of pentobarbital-anesthetized dogs without or with pretreatment with the cyclooxygenase inhibitors, indomethacin and meclofenamate. Intra-arterial administration of secretin (0.1–0.3 U/kg) produced an initial vasoconstriction followed by vasodilation. On the other hand, caerulein (50–200 ng/kg) produced vasodilation and increased pancreatic blood flow in a dose-related manner. Both secretin and caerulein increased the flow rate of pancreatic exocrine secretion. In animals pretreated with either indomethacin or meclofenamate, the ability of secretin to produce an initial vasoconstriction was abolished and the subsequent vasodilator component of the response as well as caerulein-induced vasodilation were reduced in duration. The effect of caerulein but not of secretin to stimulate the flow rate of pancreatic exocrine secretion was reduced by indomethacin and meclofenamate. Administration of PGI2 and PGE2 into the pancreas caused vasodilation, whereas PGF2 alpha and PGD2 produced a biphasic effect, i.e., an initial vasoconstriction followed by vasodilation. Infusion of either PGI2 or PGE2 but not that of PGF2 alpha or PGD2 minimized the effect of cyclooxygenase inhibitors to reduce the duration of vasodilator response elicited by secretin and caerulein. Prostaglandins neither altered the basal nor the rise in flow rate of pancreatic exocrine secretion produced by secretin and caerulein. These data indicate that in the canine pancreas prostaglandins contribute to the effects of secretin and caerulein to increase pancreatic blood flow but not to their effect on pancreatic exocrine secretion.


1990 ◽  
Vol 259 (1) ◽  
pp. E52-E56 ◽  
Author(s):  
L. Jansson ◽  
S. Sandler

Adult rats were partially depancreatized, and approximately 500 islets were isolated from each excised pancreas, maintained in tissue culture for 7 days, and subsequently transplanted back to the same animals beneath the renal capsule. Four weeks after transplantation the animals were anesthetized and given an intravenous injection of 1 ml of either saline, 30% (wt/vol) D-glucose, 30% (wt/vol) D-galactose, DL-propranolol (15 mg/kg body wt) dissolved in saline, or terbutaline (1 mg/kg body wt) dissolved in saline. Five minutes later blood perfusion of the islet grafts and the pancreatic remnant were measured with a microsphere technique. Islet blood flow was also measured in animals with pancreas intact and no islet grafts after administration of saline, glucose, or galactose. These animals demonstrated a significant and preferential increase in islet blood flow after glucose administration, whereas galactose caused a selective decrease in islet blood perfusion. Both whole pancreatic blood flow and islet blood flow in the pancreatic remnant were decreased by terbutaline administration, whereas the other substances had no effect. Blood flow to the transplanted islets was decreased by glucose and galactose, whereas propranolol and terbutaline had no effect compared with the saline-injected animals. These results suggest that blood flow regulation differs between transplanted pancreatic islets, islets in the normal pancreas, and islets in the pancreatic remnant after partial pancreatectomy. Whether this reflects lack of innervation or an altered reactivity of the newly formed blood vessels in islet grafts is presently unknown.


1996 ◽  
Vol 271 (6) ◽  
pp. E990-E995 ◽  
Author(s):  
P. O. Carlsson ◽  
A. Andersson ◽  
L. Jansson

The present study evaluated whether a microsphere technique could be used for islet blood flow measurements in anesthetized mice. When this was confirmed, we applied the technique in different strains of mice. Approximately 9 x 10(4) microspheres could be given without interfering with mean arterial blood pressure. Mixing of the microspheres with arterial blood was adequate, and the extraction of microspheres in capillary beds was nearly 100%. In NMRI mice whole pancreatic blood flow was estimated to be 0.54 +/- 0.11 ml.min-1.g pancreatic tissue-1 and islet blood flow to be 18 +/- 4 microliters.min-1.g pancreas-1 (n = 12 animals per experiment), whereas corresponding values in lean C57Bl/6 mice were twice as high. In C57Bl/6 mice glucose (3 g/kg iv) doubled islet blood flow without affecting whole pancreatic blood flow, whereas no effect was seen after an equimolar dose of 3-O-methylglucose. In obese-hyperglycemic C57Bl/6 mice, islet blood flow was more than five times higher than in the lean C57Bl/6 mice when expressed as blood flow per gram pancreas. However, when islet blood perfusion was corrected for islet weight, it was lower in the obese than in the lean mice, suggesting an impaired ability in obese mice to increase blood flow in concert with the increased islet mass. This may contribute to the insufficient insulin secretion and resulting hyperglycemia seen in these animals.


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.


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