Patients with diabetes are often treated with a statin for hyperlipidaemia and an ACE (angiotensin-converting enzyme) inhibitor or angiotensin receptor antagonist for hypertension or albuminuria. These drugs may also exert beneficial metabolic effects, causing improved glucose tolerance in patients. Gender-related differences have also been observed in the clinical responsiveness to these drugs, but the mechanism behind this is unclear. In the present study, we have investigated whether these drugs and the fatty acid palmitate influence the pancreatic microcirculation, thereby having an impact on insulin secretion and glycaemia in vivo, in spontaneously diabetic male and female Goto–Kakizaki rats. In male rats, pancreatic IBF (islet blood flow) and total PBF (pancreatic blood flow) were increased significantly by pravastatin, captopril and irbesartan. Serum insulin levels were increased by pravastatin and captopril. Palmitate suppressed pancreatic IBF and increased blood glucose. In female animals, pancreatic IBF was stimulated by captopril, candesartan and irbesartan. Total PBF was increased by captopril, candesartan and irbesartan, and by pravastatin. Palmitate suppressed pancreatic IBF and serum insulin secretion. In conclusion, the present study lends support to the view that a local pancreatic RAS (renin–angiotensin system) and pravastatin may be selectively influencing the pancreatic microcirculation and therefore affecting insulin secretion and glycaemia. NEFAs (non-esterified fatty acids) impaired pancreatic IBF, suppressed insulin secretion and increased blood glucose. Substantial gender-related differences in the vascular and metabolic responses to these drugs prevail in this animal model of diabetes.
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July 2008
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Research Article|
June 02 2008
Gender-specific regulation of pancreatic islet blood flow, insulin levels and glycaemia in spontaneously diabetic Goto–Kakizaki rats
Zhen Huang;
Zhen Huang
*Department of Internal Medicine, Karolinska Institutet, Stockholm South Hospital, SE 118 83 Stockholm, Sweden
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Leif Jansson;
Leif Jansson
†Department of Medical Cell Biology, University of Uppsala, SE-751 23 Uppsala, Sweden
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Åke Sjöholm
*Department of Internal Medicine, Karolinska Institutet, Stockholm South Hospital, SE 118 83 Stockholm, Sweden
Correspondence: Professor Åke Sjöholm (email ake.sjoholm@sodersjukhuset.se).
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Publisher: Portland Press Ltd
Received:
October 31 2007
Revision Received:
January 17 2008
Accepted:
January 21 2008
Accepted Manuscript online:
January 21 2008
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2008 Biochemical Society
2008
Clin Sci (Lond) (2008) 115 (1): 35–42.
Article history
Received:
October 31 2007
Revision Received:
January 17 2008
Accepted:
January 21 2008
Accepted Manuscript online:
January 21 2008
Citation
Zhen Huang, Leif Jansson, Åke Sjöholm; Gender-specific regulation of pancreatic islet blood flow, insulin levels and glycaemia in spontaneously diabetic Goto–Kakizaki rats. Clin Sci (Lond) 1 July 2008; 115 (1): 35–42. doi: https://doi.org/10.1042/CS20070386
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