Pancreatic and islet blood flow in F1-hybrids of the non-insulin-dependent diabetic GK-Wistar rat

Abstract

Previous studies have indicated that various conditions under which an increased functional load is posed on the pancreatic islets, e.g. partial pancreatectomy and continuous glucose infusions, may influence the microcirculation of the pancreas. To investigate further the effects of elevated functional demand on the islets, the blood perfusion of the whole pancreas and the pancreatic islets was measured with a microsphere technique in an animal model presenting impaired glucose tolerance and mild hyperglycemia, namely F1-hybrids of the spontaneously non-insulin-dependent diabetic GK-Wistar rat. Normal Wistar rats served as controls. All hybrids had a pathological intraperitoneal glucose tolerance test 1 week before the blood flow measurements, which were performed in 10-12-week-old rats. Both the whole pancreatic and the islet blood flows were increased in the hybrids compared to controls. The fractional islet blood flow, i.e. the fraction of whole pancreatic blood flow diverted through the islets, also was increased in the hybrid rats (12.6 +/- 0.6% vs 9.8 +/- 0.5% in controls, p < 0.01). A bilateral abdominal vagotomy performed 30 min before the blood flow measurement markedly decreased the blood flow values of the islets and the whole pancreas in both groups of rats. After vagotomy, the islet blood flow in the hybrid rats was similar to that of the vagotomized control animals (8.2 +/- 0.8 and 7.5 +/- 1.4%, respectively). It is concluded that the increased pancreatic and islet blood perfusion observed in F1-hybrids of the GK-Wistar rat depends on a mechanism mediated by the vagus nerve.

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

“…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.…”

“…Although neuropathic changes are known to occur in diabetic GK rats [49,50], an even more pronounced decrease in islet blood flow occurred in the GK rats than in normal rats. Of interest, diabetic GK rats and their hybrids have been shown to have an increased islet blood flow during normal conditions dependent on a glucose-dependent mechanism mediated by the vagus nerve [11,13]. Whether also the more pronounced hypoglycaemia-induced decrease in islet blood flow in GK rats compared to normal rats, relates to changed vagal nervous activity is not known.…”

“…Although the decrease was not as substantial as that in islet blood flow, especially GK rats but also their F 1 -hybrids, responded with a pronounced decrease in total pancreatic blood flow to insulin-induced hypoglycaemia. Not only islet blood flow, but also whole pancreatic blood flow, have been observed to depend on an increased vagal nervous activity in GK rats and their F1-hybrids [11,47].…”

Young capillary vessels rejuvenate aged pancreatic islets

“…Our study now shows that the islet as an organ seems to be threatened by factors that affect vascular function. The increased functional demand aged islets face may lead to increased islet blood flow (43,44), which in turn may trigger increased capillary pressure and compromise islet microcirculation (45). In addition, with aging, the vascular phenotype makes a proinflammatory shift that contributes to endothelial dysfunction (46).…”

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

“…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.…”