Lack of compensatory increase in islet blood flow and islet mass in GK rats following 60% partial pancreatectomy

Svensson, Annika; Östenson, Claes‐Göran; Bodin, Birgitta; Jansson, Leif

doi:10.1677/joe.1.05676

Cited by 7 publications

(11 citation statements)

References 47 publications

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“…Our findings on GIP effects on glucose homeostasis were thus in line with previous studies and confirm the physiological effects of the used doses (Svensson et al. , ).…”

Section: Discussionsupporting

confidence: 93%

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Effects of GIP on regional blood flow during normoglycemia and hyperglycemia in anesthetized rats

et al. 2018

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The incretin hormone glucose‐dependent insulinotropic polypeptide (GIP) potentiates glucose‐stimulated insulin secretion, and affects β‐cell turnover. This study aimed at evaluating if some of the beneficial effects of GIP on glucose homeostasis can be explained by modulation of islet blood flow. Anesthetized Sprague–Dawley rats were infused intravenously with different doses of GIP (10, 20, or 60 ng/kg*min) for 30 min. Subsequent organ blood flow measurements were performed with microspheres. In separate animals, islets were perfused ex vivo with GIP (10−6–10−12 mol/L) during normo‐ and hyperglycemia and arteriolar responsiveness was recorded. The highest dose of GIP potentiated insulin secretion during hyperglycemia, but had no effect in normoglycemic rats. The highest GIP concentration decreased blood perfusion of whole pancreas, pancreatic islets, duodenum, colon, liver and kidneys. The decrease in blood flow was unaffected by ganglion blockade or adenosine receptor inhibition. In contrast to this, in single perfused islets GIP induced a dose‐dependent arteriolar dilation. Thus, high doses of GIP exert a direct dilatory effect on islet arterioles in isolated islets, but induce a generalized vasoconstriction in splanchnic organs, including the whole pancreas and islets, in vivo. The latter effect is unlikely to be mediated by adenosine, the autonomic nervous system, or endothelial mediators.

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“…Our findings on GIP effects on glucose homeostasis were thus in line with previous studies and confirm the physiological effects of the used doses (Svensson et al. , ).…”

Section: Discussionsupporting

confidence: 93%

“…In contrast, during hyperglycemia the highest GIP-dose potentiated glucose-induced insulin secretion. Our findings on GIP effects on glucose homeostasis were thus in line with previous studies and confirm the physiological effects of the used doses (Svensson et al 2000(Svensson et al , 2005.…”

Section: Discussionsupporting

confidence: 92%

Effects of GIP on regional blood flow during normoglycemia and hyperglycemia in anesthetized rats

et al. 2018

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“…GK rats might present a deficient angiogenesis due to lack of VEGF response and also possible eNOS uncoupling, because VEGF-induced-eNOS is an efficient pathway of angiogenesis [110], [111] as well as COX-2 [112]. In this context, the lack for GK rats to increase blood flow and islet mass after 60% pancreatectomy as opposed to Wistar rats should be noted [113].…”

Section: Discussionmentioning

confidence: 99%

Islet Endothelial Activation and Oxidative Stress Gene Expression Is Reduced by IL-1Ra Treatment in the Type 2 Diabetic GK Rat

et al. 2009

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BackgroundInflammation followed by fibrosis is a component of islet dysfunction in both rodent and human type 2 diabetes. Because islet inflammation may originate from endothelial cells, we assessed the expression of selected genes involved in endothelial cell activation in islets from a spontaneous model of type 2 diabetes, the Goto-Kakizaki (GK) rat. We also examined islet endotheliuml/oxidative stress (OS)/inflammation-related gene expression, islet vascularization and fibrosis after treatment with the interleukin-1 (IL-1) receptor antagonist (IL-1Ra).Methodology/Principal FindingsGene expression was analyzed by quantitative RT-PCR on islets isolated from 10-week-old diabetic GK and control Wistar rats. Furthermore, GK rats were treated s.c twice daily with IL-1Ra (Kineret, Amgen, 100 mg/kg/day) or saline, from 4 weeks of age onwards (onset of diabetes). Four weeks later, islet gene analysis and pancreas immunochemistry were performed. Thirty-two genes were selected encoding molecules involved in endothelial cell activation, particularly fibrinolysis, vascular tone, OS, angiogenesis and also inflammation. All genes except those encoding angiotensinogen and epoxide hydrolase (that were decreased), and 12-lipoxygenase and vascular endothelial growth factor (that showed no change), were significantly up-regulated in GK islets. After IL-1Ra treatment of GK rats in vivo, most selected genes implied in endothelium/OS/immune cells/fibrosis were significantly down-regulated. IL-1Ra also improved islet vascularization, reduced fibrosis and ameliorated glycemia.Conclusions/SignificanceGK rat islets have increased mRNA expression of markers of early islet endothelial cell activation, possibly triggered by several metabolic factors, and also some defense mechanisms. The beneficial effect of IL-1Ra on most islet endothelial/OS/immune cells/fibrosis parameters analyzed highlights a major endothelial-related role for IL-1 in GK islet alterations. Thus, metabolically-altered islet endothelium might affect the β-cell microenvironment and contribute to progressive type 2 diabetic β-cell dysfunction in GK rats. Counteracting islet endothelial cell inflammation might be one way to ameliorate/prevent β-cell dysfunction in type 2 diabetes.

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“…A study on hyperglycemic Goto-Kakizaki (GK) rats showed that following a 60% pancreatectomy, GK rats are unable to compensate for decreased beta-cell mass by increasing islet blood flow in contrast to normal animals [15] . And islet hyperperfusion during the pre-obese and pre-diabetic state was found in a rat model of obesity and type 2 diabetes [16] .…”

Section: Discussionmentioning

confidence: 99%

Effect of renin angiotensin system blockade on the islet microvessel density of diabetic rats and its relationship with islet function

et al. 2009

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin (30 mg/kg). After 8 weeks intervention with perindopril (AE, n=10) or valsartan (AR, n=10), the islet function of the animals was evaluated by intravenous insulin release test (IVIRT). The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor (VEGF) in the islets. The microvessel density (MVD) of islets was detected by counting CD34 positive cells. The hypoxia inducible factor (HIF)-1alpha mRNA expression in the islets was detected by RT-PCR. Compared with normal control group (NC, n=10), the area under the curve for insulin from 0 to 30 min (AUCI(0-30)) of diabetes group (DM, n=8) was decreased by 66.3%; the insulin relative concentration (IRC) of betacell was decreased significantly; the relative content of VEGF was increased obviously [(-4.21+/-0.13) vs (-4.06+/-0.29)]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1alpha mRNA was increased by 1.19 times (all P<0.01). Compared with DM group, the AUCI(0-30) of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1alpha was decreased by 27.2% and 29.0% respectively (all P<0.01 or P<0.05). There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.

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Lack of compensatory increase in islet blood flow and islet mass in GK rats following 60% partial pancreatectomy

Cited by 7 publications

References 47 publications

Effects of GIP on regional blood flow during normoglycemia and hyperglycemia in anesthetized rats

Effects of GIP on regional blood flow during normoglycemia and hyperglycemia in anesthetized rats

Islet Endothelial Activation and Oxidative Stress Gene Expression Is Reduced by IL-1Ra Treatment in the Type 2 Diabetic GK Rat

Effect of renin angiotensin system blockade on the islet microvessel density of diabetic rats and its relationship with islet function

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