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

Abstract

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

Pancreatic islet blood flow during euglycaemic, hyperinsulinaemic clamp in anaesthetized rats

“…We have previously shown that hypoglycaemia decreases islet blood perfusion, mainly through signalling mediated through the vagus nerve (Carlsson et al 2003). This is in contrast to findings in other studies, where an unchanged or increased islet blood flow was measured after acute insulin administration (Sparrow & Beckingham 1989, Iwase et al 2001.…”

“…This increased flow is usually, but not necessarily, associated with an increased insulin secretion (Jansson 1985. In contrast to this we found that hypoglycaemia induces a decreased islet blood perfusion mediated through signals transmitted via the vagus nerve (Carlsson et al 2003). Thus, in some studies administration of exogenous insulin did not affect (Iwase et al 2001) or increased islet blood flow (Sparrow & Beckingham 1989), whereas the hypoglycaemic agent tolbutamide also increased islet blood flow (Vetterlein et al 1985).…”

“…Thus, in some studies administration of exogenous insulin did not affect (Iwase et al 2001) or increased islet blood flow (Sparrow & Beckingham 1989), whereas the hypoglycaemic agent tolbutamide also increased islet blood flow (Vetterlein et al 1985). In contrast to this we found that hypoglycaemia induces a decreased islet blood perfusion mediated through signals transmitted via the vagus nerve (Carlsson et al 2003).…”

“…rats with a denervated pancreas) or animals given 2-deoxy glucose (Carlsson et al 2003). As previously demonstrated this is due to an activation of the vagus nerve as shown in wholepancreas transplanted rats (i.e.…”

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

“…In support of this, we have observed that most drugs used to treat diabetes in experimental animal models increase islet blood flow in control animals, but normalize islet blood flow in T2D animals (Jansson ; Carlsson et al. ). It may be that incretins exert additional beneficial effects on pancreatic islet function through actions on islet blood flow.…”