scholarly journals Angiotensin II and the endocrine pancreas: effects on islet blood flow and insulin secretion in rats

Diabetologia ◽  
1998 ◽  
Vol 41 (2) ◽  
pp. 127-133 ◽  
Author(s):  
P.-O. Carlsson ◽  
C. Berne ◽  
L. Jansson
Keyword(s):  
Blood Flow ◽  
Insulin Secretion ◽  
Angiotensin Ii ◽  
Endocrine Pancreas ◽  
Islet Blood Flow

Angiotensin II type 1 receptor antagonists prevent glucose‐induced increases in islet blood flow in rats

2009 ◽  
Vol 69 (1) ◽  
pp. 145-150 ◽  
Author(s):  
Masanori Iwase ◽  
Yuji Uchizono ◽  
Sakae Nohara ◽  
Nobuhiro Sasaki ◽  
Kazuo Sonoki ◽  
...  
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Receptor Antagonists ◽  
Islet Blood Flow

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

1996 ◽  
Vol 298 (3) ◽  
pp. 287-292 ◽  
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

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

1992 ◽  
Vol 262 (5) ◽  
pp. E736-E740 ◽  
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.

Gender-specific regulation of pancreatic islet blood flow, insulin levels and glycaemia in spontaneously diabetic Goto–Kakizaki rats

2008 ◽  
Vol 115 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Zhen Huang ◽  
Leif Jansson ◽  
Åke Sjöholm
Keyword(s):  
Blood Flow ◽  
Insulin Secretion ◽  
Blood Glucose ◽  
Enzyme Inhibitor ◽  
Serum Insulin ◽  
Metabolic Effects ◽  
Male Rats ◽  
Insulin Levels ◽  
Islet Blood Flow ◽  
Specific Regulation

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.

Age-induced changes in pancreatic islet blood flow: evidence for an impaired regulation in diabetic GK rats

2000 ◽  
Vol 279 (5) ◽  
pp. E1139-E1144 ◽  
Author(s):  
Annika M. Svensson ◽  
Claes-Göran Östenson ◽  
Leif Jansson
Keyword(s):  
Blood Flow ◽  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Blood Perfusion ◽  
Flow Measurements ◽  
Gk Rats ◽  
Islet Blood Flow ◽  
Longitudinal Variations ◽  
Increasing Demand ◽  
Blood Flow Measurements

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.

scholarly journals Optogenetic Stimulation of Pancreatic Function via Vagal Cholinergic Axons

2019 ◽  
Author(s):  
Arjun K. Fontaine ◽  
David G. Ramirez ◽  
Samuel F. Littich ◽  
Robert A. Piscopio ◽  
Vira Kravets ◽  
...  
Keyword(s):  
Blood Flow ◽  
Insulin Secretion ◽  
Endocrine Pancreas ◽  
Therapeutic Potential ◽  
Serum Insulin ◽  
Flow Measurements ◽  
Optical Stimulation ◽  
Excitation Light ◽  
Pancreas Function ◽  
Stimulation Of

AbstractPrevious studies have demonstrated stimulation of endocrine pancreas function by vagal nerve electrical stimulation. While this increases insulin secretion; concomitant reductions in circulating glucose do not occur. A complicating factor is the non-specific nature of electrical nerve stimulation. Optogenetic tools enable high specificity in neural stimulation using cell-type specific targeting of opsins and/or spatially shaped excitation light. Here, we demonstrate light-activated stimulation of the endocrine pancreas by targeting vagal parasympathetic axons. In a mouse model expressing ChannelRhodopsin2 (ChR2) in cholinergic cells, serum insulin and glucose were measured in response to both ultrasound image-guided optical stimulation of axon terminals in the pancreas and optical stimulation of axons of the cervical vagus nerve, together with ultrasound-based measures of pancreas blood flow. Measurements were made in basal-glucose and glucose-stimulated conditions. Significant increases in plasma insulin occurred relative to controls under both pancreas and vagal stimulation, accompanying rapid reductions in glycemic levels. Additionally, a significant increase in pancreatic blood flow was measured following optical stimulation. Together, these results demonstrate the utility of in-vivo optogenetics for studying the neural regulation of endocrine pancreas function and suggest therapeutic potential for the control of insulin secretion and glucose homeostasis.

Glucose intolerance and reduced islet blood flow in transgenic mice expressing the FRK tyrosine kinase under the control of the rat insulin promoter

2007 ◽  
Vol 292 (4) ◽  
pp. E1183-E1190 ◽  
Author(s):  
Cecilia Annerén ◽  
Michael Welsh ◽  
Leif Jansson
Keyword(s):  
Blood Flow ◽  
Insulin Secretion ◽  
Transgenic Mice ◽  
Tyrosine Kinase ◽  
Cell Mass ◽  
Β Cells ◽  
Β Cell ◽  
Islet Blood Flow ◽  
Insulin Promoter

The FRK tyrosine kinase has previously been shown to transduce β-cell cytotoxic signals in response to cytokines and streptozotocin and to promote β-cell proliferation and an increased β-cell mass. We therefore aimed to further evaluate the effects of overexpression of FRK tyrosine kinase in β-cells. A transgenic mouse expressing kinase-active FRK under control of the insulin promoter (RIP-FRK) was studied with regard to islet endocrine function and vascular morphology. Mild glucose intolerance develops in RIP-FRK male mice of at least 4 mo of age. This effect is accompanied by reduced glucose-stimulated insulin secretion in vivo and reduced second-phase insulin secretion in response to glucose and arginine upon pancreas perfusion. Islets isolated from the FRK transgenic mice display a glucose-induced insulin secretory response in vitro similar to that of control islets. However, islet blood flow per islet volume is decreased in the FRK transgenic mice. These mice also exhibit a reduced islet capillary lumen diameter as shown by electron microscopy. Total body weight and pancreas weight are not significantly affected, but the β-cell mass is increased. The data suggest that long-term expression of active FRK in β-cells causes an in vivo insulin-secretory defect, which may be the consequence of islet vascular abnormalities that yield a decreased islet blood flow.

Vasoactive drugs enhance pancreatic islet blood flow, augment insulin secretion and improve glucose tolerance in female rats

2006 ◽  
Vol 112 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Zhen Huang ◽  
Leif Jansson ◽  
Åke Sjöholm
Keyword(s):  
Blood Flow ◽  
Body Weight ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Pancreatic Islet ◽  
Renin Angiotensin System ◽  
Female Rats ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Islet Blood Flow

Pravastatin, irbesartan and captopril are frequently used in the treatment of patients with Type 2 diabetes. These drugs also exert beneficial metabolic effects, causing an improved glucose tolerance in patients, but the precise mechanisms by which this is achieved remain elusive. To this end, we have studied whether these drugs influence insulin secretion in vivo through effects on islet blood perfusion. Captopril (3 mg/kg of body weight), irbesartan (3 mg/kg of body weight) and pravastatin (0.5 mg/kg of body weight) were injected intravenously into anaesthetized female Wistar rats. Blood flow rates were determined by a microsphere technique. Blood glucose concentrations were measured with test reagent strips and serum insulin concentrations were measured by ELISA. Pancreatic blood flow was markedly increased by pravastatin (P<0.001), captopril (P<0.05) and irbesartan (P<0.01). Pancreatic islet blood flow was significantly and preferentially enhanced after the administration of captopril (P<0.01), irbesartan (P<0.01) and pravastatin (P<0.001). Kidney blood flow was enhanced significantly by pravastatin (P<0.01), irbesartan (P<0.05) and captopril (P<0.01). Captopril and pravastatin also enhanced late-phase insulin secretion and positively influenced glycaemia in intraperitoneal glucose tolerance tests. In conclusion, the present study suggests that a local pancreatic renin–angiotensin system and pravastatin treatment may be selectively controlling pancreatic islet blood flow, augmenting insulin secretion and thereby improving glucose tolerance. Our findings indicate significant gender-related differences in the vascular response to these agents. Since statins and renin–angiotensin system inhibitors are frequently used by diabetic patients, the antidiabetic actions of these drugs reported previously might occur, in part, through the beneficial direct islet effects shown in the present study.

scholarly journals Pancreatic islet blood flow during pregnancy in the rat: an increased islet mass is associated with decreased islet blood flow

2004 ◽  
Vol 180 (3) ◽  
pp. 409-415 ◽  
Author(s):  
AM Svensson ◽  
B Bodin ◽  
A Andersson ◽  
L Jansson
Keyword(s):  
Blood Flow ◽  
Insulin Secretion ◽  
Post Partum ◽  
Blood Perfusion ◽  
Late Pregnancy ◽  
Vascular Density ◽  
Total Blood ◽  
Islet Mass ◽  
Islet Blood Flow ◽  
Islet Tissue

Increased blood perfusion of pancreatic islets is seen during various conditions of increased demand for insulin secretion. Pregnancy confers an increased need for insulin secretion, met by increased islet mass and volume as well as a decreased threshold for glucose-induced insulin secretion. In the present study, whole pancreatic and islet blood flow were studied with a microsphere technique in Wistar rats on days 15, 18 and 20 of pregnancy and days 2 and 7 post-partum. There were no changes in total pancreatic blood flow during pregnancy and the first post-partum week. Total blood perfusion through islet tissue expressed as flow per weight of whole pancreas was higher at day 15 of pregnancy. When islet blood flow was expressed per gram of islet tissue there was a decrease at day 18 of pregnancy. This decrease of islet blood flow was concomitant to a short-lived increase of the islet mass at the end of pregnancy. We conclude that upregulation of insulin output during late pregnancy does not specifically include increased net blood perfusion through the islets. One possible reason for this might be lack of synchronization between the proliferation of endocrine cells and angiogenesis, resulting in a relative decrease in islet vascular density in the islets.

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