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

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

doi:10.1152/ajpendo.2000.279.5.e1139

Cited by 40 publications

(33 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In general, increased functional demands on the pancreatic islets are associated with an islet blood hyperperfusion [1]. In line with this, an increased islet blood flow is seen in Type 2 diabetic GK rats and their F 1 -hybrids, but also disturbances in islet blood flow regulation [10,11,13,47,48]. The decreased islet blood perfusion that we observed in normal rats in response to hypoglycaemia is theoretically advantageous during hypoglycaemia, as it could reduce the dispersal of insulin to the peripheral circulation, thereby diminishing the degree of hypoglycaemia.…”

Section: Discussionmentioning

confidence: 71%

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: 71%

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

“…In the tolbutamide study, young rats, aged 5 weeks, were used, whereas we studied adult rats ϳ15 weeks old. We have previously noted marked differences in the absolute values in islet blood flow depending on the age of the animals, and it is also likely that the blood flow regulation differs (37,38). It is also possible that there are differences in the actions of tolbutamide and glipizide, although this seems less likely.…”

Section: Discussionmentioning

confidence: 98%

KATP Channels and Pancreatic Islet Blood Flow in Anesthetized Rats

et al. 2003

Self Cite

View full text Add to dashboard Cite

K ATP channels are important for insulin secretion and depolarization of vascular smooth muscle. In view of the importance of drugs affecting K ATP channels in the treatment of diabetes, we investigated the effects of these channels on splanchnic blood perfusion in general and pancreatic islet blood flow in particular. We treated anesthetized Sprague-Dawley rats with the K ATP channel openers diazoxide or NNC 55-0118 or the K ATP channel closer glipizide. Both diazoxide and NNC 55-0118 dose-dependently increased total pancreatic and islet blood flow in the presence of moderate hyperglycemia, but had no effects on the blood perfusion of other splanchnic organs. Diazoxide markedly lowered the mean arterial blood pressure and thus increased vascular conductance in all organs studied. NNC 55-0118 had much smaller effects on the blood pressure. Glipizide did not affect total pancreatic blood flow, but decreased islet blood flow by 50% in the presence of hypoglycemia. We conclude that K ATP channels actively participate in the blood flow regulation of the pancreatic islets and that substances affecting such channels may also influence islet blood flow.

show abstract

“…Age-related changes in islet blood flow have been studied in ob/ob mice (19) and GK rats (20). In these studies, islet blood flow was higher in 1-month-old ob/ob mice and in 5-and 12-week-old GK rats than in age-matched controls, when these animals had already developed obesity and/or overt diabetes.…”

Section: Discussionmentioning

confidence: 99%

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

Iwase

Uchizono²,

Tashiro³

et al. 2002

Diabetes

View full text Add to dashboard Cite

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.

show abstract

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

Cited by 40 publications

References 36 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

KATP Channels and Pancreatic Islet Blood Flow in Anesthetized Rats

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

Contact Info

Product

Resources

About