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

Iwase, Masanori; Uchizono, Yuji; Tashiro, Kotaro; Goto, Daisuke; Iida, Mitsuo

doi:10.2337/diabetes.51.8.2530

Cited by 32 publications

(24 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reasons for the discrepancy between these studies are not known. Compared to most studies on islet blood flow in adult rats [1,10,12,31,32] one group [14] obtained a considerably lower value (~2% vs 7-20%) for the control rats. Such low islet blood flow values have previously only been recorded in very young animals [16,33,34].…”

Section: Discussionmentioning

confidence: 72%

Hypoglycaemia induces decreased islet blood perfusion mediated by the central nervous system in normal and Type 2 diabetic GK rats

et al. 2003

View full text Add to dashboard Cite

Aims/hypothesis. The aim of this study was to evaluate the effects of induced hypoglycaemia on pancreatic-islet blood flow in normal rats and in the GK rat, an animal model of Type 2 diabetes which normally has an increased islet blood perfusion. Methods. A 50% reduction in blood glucose concentrations was achieved by intravenous administration of a rapidly acting insulin (15 IU/kg body weight). Blood flows were measured by a non-radioactive microsphere technique. Results. A pronounced decrease in islet blood flow was observed in all animals, but preferentially in the Type 2 diabetic GK rats. When a similar dose of insulin was given to whole-pancreas transplanted rats only islet blood flow in the native pancreas was decreased, whereas that of the transplanted, i.e. denervated, pancreas was unchanged. Administration of 2-deoxy-Dglucose, which induces intracellular glucopenia especially in neurons, also decreased islet blood flow despite a systemic hyperglycaemia. Conclusion/interpretation. Hypoglycaemia leads to a preferential decrease in pancreatic-islet blood perfusion. The effect is probably mediated by the central nervous system, since 2-deoxy D-glucose-induced neuronal glucopenia caused a similar decrease in blood flow. The effects of islet blood flow are not likely to be mediated by nervous stimulation of the adrenal glands, with an associated release of catecholamines, because the transplanted pancreas was not affected by hypoglycaemia. The decreased islet blood perfusion could possibly diminish the output of insulin from the islets, thereby preventing a further decrease in blood glucose concentrations. [Diabetologia (2003[Diabetologia ( ) 46:1124[Diabetologia ( -1130

show abstract

Section: Discussionmentioning

confidence: 72%

Hypoglycaemia induces decreased islet blood perfusion mediated by the central nervous system in normal and Type 2 diabetic GK rats

et al. 2003

View full text Add to dashboard Cite

show abstract

“…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] . Islet hypoperfusion was noted in long-term hyperglycemia [17] .…”

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.]

View full text Add to dashboard Cite

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.

show abstract

“…5). Whether the glucose-induced increase in islet blood flow may be detrimental under pathological states like chronic hyperglycemia is not known (11). Likewise, the reduced islet blood flow during hypoglycemia suggests that a glucose level below the physiological range slows insulin delivery into the systemic circulation, as would be desired during hypoglycemia.…”

Section: Discussionmentioning

confidence: 99%

Glucose-dependent blood flow dynamics in murine pancreatic islets in vivo

Nyman

Ford

Powers

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Pancreatic islets are highly vascularized and arranged so that regions containing ␤-cells are distinct from those containing other cell types. Although islet blood flow has been studied extensively, little is known about the dynamics of islet blood flow during hypoglycemia or hyperglycemia. To investigate changes in islet blood flow as a function of blood glucose level, we clamped blood glucose sequentially at hyperglycemic (ϳ300 mg/dl or 16.8 mM) and hypoglycemic (ϳ50 mg/dl or 2.8 mM) levels while simultaneously imaging intraislet blood flow in mouse models that express green fluorescent protein in the ␤-cells or yellow fluorescent protein in the ␣-cells. Using line scanning confocal microscopy, in vivo blood flow was assayed after intravenous injection of fluorescent dextran or sulforhodamine-labeled red blood cells. Regardless of the sequence of hypoglycemia and hyperglycemia, islet blood flow is faster during hyperglycemia, and apparent blood volume is greater during hyperglycemia than during hypoglycemia. However, there is no change in the order of perfusion of different islet endocrine cell types in hypoglycemia compared with hyperglycemia, with the islet core of ␤-cells usually perfused first. In contrast to the results in islets, there was no significant difference in flow rate in the exocrine pancreas during hyperglycemia compared with hypoglycemia. These results indicate that glucose differentially regulates blood flow in the pancreatic islet vasculature independently of blood flow in the rest of the pancreas.THE ISLETS OF LANGERHANS are highly vascularized miniorgans within the pancreas. Researchers have long observed an intimate relationship between pancreatic islets and their distinguished vasculature (7). The vessels within the islet are more numerous and more tortuous than vessels in the surrounding exocrine tissue (2, 4). These characteristics of islet vasculature are likely related to the islets' function of sensing and responding to changes in blood glucose. The morphology of the pancreatic islet is notable in that regions containing ␤-cells are distinct from those containing ␣-and ␦-cells (19). However, investigations of the physiological importance of this distinct cellular organization of the islet and its vasculature are limited (19,26,27).Prior studies have shown two predominant islet blood flow patterns in murine islets (6,18,23,25). The most common pattern is where the blood initially perfuses the islet core and then the islet perimeter (3,18,22,25). In the second pattern, blood flows from one side of the islet to the other side, and thus perfuses core and perimeter areas simultaneously (16,18). The majority of these experimental data, however, have been gathered irrespective of blood glucose levels. Thus, little is known about islet blood flow during different metabolic states or changes in blood glucose levels. Since it has been suggested that glucose and/or insulin levels affect blood flow (10), we examined the islet blood flow dynamics as a function of blood glucose level.To examine ...

show abstract

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

Cited by 32 publications

References 39 publications

Hypoglycaemia induces decreased islet blood perfusion mediated by the central nervous system in normal and Type 2 diabetic GK rats

Hypoglycaemia induces decreased islet blood perfusion mediated by the central nervous system in normal and Type 2 diabetic GK rats

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

Glucose-dependent blood flow dynamics in murine pancreatic islets in vivo

Contact Info

Product

Resources

About