Peut-on espérer une régression de la neuropathie diabétique après transplantation d’îlots ? Résultats d’une étude expérimentale chez le rat

Abstract

Aims/hypothesis

Type 1 diabetes is a chronic disease leading to complications such as peripheral neuropathies, nephropathy, and cardiovascular disease. Pancreatic islet transplantation is being extensively investigated for blood glucose control in animals and in patients with type 1 diabetes; however, the question of whether it can reverse long-term diabetic complications has not been fully explored. We investigated the effects of islet transplantation on diabetic complications in a rat model of streptozotocin-induced diabetes.

Methods

Three groups of rats were used: healthy controls, diabetic rats, and diabetic rats transplanted with microencapsulated islets at 2 months after diabetes induction, when neuropathywas detectable by a decrease in tail nerve conduction velocity (NCV) and impaired nociceptive thresholds. Blood glucose levels and body weight were measured weekly. The variables considered were as follows: thermal (hot platetest) and mechanical sensitivity (Randal-Selitto paw withdrawal test), NCV, and Na+, K+-ATPase activity in the sciatic nerve. At the end of the experiments, hearts were removed for morphometric determination and myocyte number, and kidneys were removed for histological examination.

Results

Islet transplantation in diabetic rats induced normoglycemia in a few days, accompanied by a rapid rise in body weight and amelioration of impaired nociceptive thresholds, as well as normalization of NCV and Na+, K+-ATPase, which were both about 25% below normal in diabetic rats. Myocyte loss was reduced (−34%) by islet transplantation, and the observed mild kidney damage of diabetic rats was prevented.

Conclusions/Interpretation

Besides controlling glycemia, transplantation of microencapsulated pancreatic islets induced almostcomplete regression of neuropathy and prevented cardiovascular alterations.