The pancreatic islets in spontaneously hypertensive rats: islet blood flow and insulin production

Iwase, Masanori; Sandler, Stellan; Carlsson, Per‐Ola; Hellerström, Claes; Jansson, Leif

doi:10.1530/eje.0.1440169

Cited by 18 publications

(10 citation statements)

References 43 publications

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“…Changes in pancreatic islet microcirculation may impede insulin output in diabetic subjects, and could contribute to the pathogenesis of the disease. Islet hyperperfusion and abnormal modulation of IBF (islet blood flow) after glucose challenge have been observed in various animal models of glucose intolerance and diabetes, including obese animals [3] as well as the non-obese GK (Goto-Kakizaki) rats [4].…”

Section: Introductionmentioning

confidence: 99%

GLP-1, exendin-4 and C-peptide regulate pancreatic islet microcirculation, insulin secretion and glucose tolerance in rats

Olverling

Zhen

et al. 2011

Clinical Science

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GLP-1 (glucagon-like peptide 1) and its mimetic exendin-4 are used against Type 2 diabetes. C-peptide has also proven promising to enhance insulin action. Since insulin secretion in vivo can be rapidly tuned by changes in islet microcirculation, we evaluated the influence of GLP-1, exendin-4 and C-peptide on pancreatic IBF (islet blood flow), and dynamic changes in insulin secretion and glycaemia in the rat. Adult male Wistar rats were divided into four groups given intravenous saline, GLP-1, exendin-4 or C-peptide respectively and administered either saline or 30% glucose. Furthermore, we investigated the effect of intravenous infusion of different doses of exendin-4 into either the femoral vein or the portal vein on islet microcirculation. A non-radioactive microsphere technique was adopted to measure the regional blood flow. Both GLP-1 and exendin-4 prevented the glucose-induced PBF (pancreatic blood flow) redistribution into the islets. Infusion of exendin-4 into the portal vein did not alter pancreatic islet microcirculation, while infusion of exendin-4 into femoral vein significantly decreased basal IBF. C-peptide increased basal IBF and the proportion of IBF out of total PBF, but did not affect the islet microcirculation after glucose administration. GLP-1, exendin-4 and C-peptide stimulated insulin secretion and significantly decreased glycaemia. Blocking NO formation did not prevent the decreased IBF and post-load glycaemia evoked by exendin-4, but further decreased IBF and KBF (kidney blood flow) and increased basal glycaemia. Blocking the vagus nerve enhanced pancreatic IBF and further decreased post-load glycaemia and KBF and increased basal glycaemia. The vascular modulatory effect on pancreatic islet microcirculation described herein, with subsequent effects on in vivo insulin secretion and glycaemia, might be one of the mechanisms underlying the anti-diabetic actions of GLP-1 and its long acting mimetic exendin-4, as well as that of C-peptide.

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Section: Introductionmentioning

confidence: 99%

GLP-1, exendin-4 and C-peptide regulate pancreatic islet microcirculation, insulin secretion and glucose tolerance in rats

Olverling

Zhen

et al. 2011

Clinical Science

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“…The regulatory mechanisms that control islet blood flow are complex and include neural, hormonal, and local mechanisms that are independent of the surrounding exocrine pancreas (5). It has been reported that islet blood flow is altered in rodent models with type 1 (6) or type 2 diabetes (7,8), obesity (9 -11), and hypertension (12). Although it has been suggested that changes in islet blood flow may be closely relevant to changes in islet function and metabolism, the relationship between flow and function is not fully understood.…”

mentioning

confidence: 99%

Islet Hyperperfusion During Prediabetic Phase in OLETF Rats, a Model of Type 2 Diabetes

Iwase

Uchizono²,

Tashiro³

et al. 2002

Diabetes

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Although it has been hypothesized that initial hyperperfusion followed by late hypoperfusion in islet circulation occurs in rodent models of type 2 diabetes, islet blood flow has not been measured during prediabetic phase. We studied islet blood flow in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of slowly progressive obese type 2 diabetes. Islet blood flow was measured by the two-color microsphere method under anesthesia at different ages. Islet blood flow was significantly higher in young OLETF rats compared with control Long-Evans Tokushima Otsuka (LETO) rats when the former were not obese or diabetic and had normal insulin secretion at 5 weeks of age (LETO 4.6 ؎ 1.1, OLETF 8.8 ؎ 1.2 ml ⅐ min ؊1 ⅐ mg ؊1 , P < 0.01). At 6 months of age, islet hyperperfusion was observed in OLETF rats, and >40% of whole pancreatic blood flow was diverted into islets in OLETF rats. Prevention of obesity by food restriction increased basal islet blood flow. On the other hand, long-term hyperglycemia induced by sucrose feeding decreased fractional islet blood flow as well as glucose-stimulated islet blood flow. Our results indicate that hyperperfusion is present during the preobese and prediabetic phase in our type 2 diabetes rats.

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“…In spite of this, we saw no major changes in organ blood flows, besides an increase in adrenal, total pancreatic and islet blood flow. This is unlikely to be due to the increased mean arterial blood pressure, since we have previously shown that this is well within the interval in which these blood flow values are autoregulated (34). That also islet blood flow increases, is surprising in view of the sensitivity of islets to NO (see above).…”

Section: Discussionmentioning

confidence: 79%

Arginase Increases Total Pancreatic and Islet Blood Flow in Anaesthetized Mice

Jansson

Bodin

Källskog

2007

Upsala Journal of Medical Sciences

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Background. Previous studies have demonstrated that the high basal pancreatic islet blood perfusion is crucially dependent on nitric oxide formation. Arginase can interfere with the formation of nitric oxide by limiting substrate availability. The aim of the present study was to evaluate the influence of arginase on islet blood perfusion in anasthetized mice.Methods. The blood perfusion of the pancreatic islets was measured with a microsphere technique in anaesthetized NMRI mice after administration of arginase.Results: Arginase administration increased both total pancreatic and islet blood flow to the same degree. Also adrenal blood flow was increased, whereas other organ blood flow values were unaffected.Conclusion. Arginase induces a paradoxical increase in pancreatic and islet blood flow, the reasons for which are still unknown.

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The pancreatic islets in spontaneously hypertensive rats: islet blood flow and insulin production

Cited by 18 publications

References 43 publications

GLP-1, exendin-4 and C-peptide regulate pancreatic islet microcirculation, insulin secretion and glucose tolerance in rats

GLP-1, exendin-4 and C-peptide regulate pancreatic islet microcirculation, insulin secretion and glucose tolerance in rats

Islet Hyperperfusion During Prediabetic Phase in OLETF Rats, a Model of Type 2 Diabetes

Arginase Increases Total Pancreatic and Islet Blood Flow in Anaesthetized Mice

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