Regression of diabetic complications by islet transplantation in the rat

Diabetologia. 2009 Dec;52(12):2653-61. doi: 10.1007/s00125-009-1537-y. Epub 2009 Sep 30.

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 human type 1 diabetic patients, but 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 and diabetic rats transplanted with microencapsulated islets at 2 months after diabetes induction, when neuropathy was 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: thermal (hot plate test) 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 removed for histological examination.

Results: Islet transplantation in diabetic rats induced normoglycaemia in a few days, accompanied by a rapid rise in body weight and amelioration of impaired nociceptive thresholds, as well as normalisation 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 glycaemia, transplantation of microencapsulated pancreatic islets induced almost complete regression of neuropathy and prevented cardiovascular alterations.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Complications / prevention & control*
  • Diabetes Complications / surgery
  • Diabetic Neuropathies / epidemiology
  • Diabetic Neuropathies / mortality
  • Diabetic Neuropathies / prevention & control*
  • Diabetic Neuropathies / surgery
  • Humans
  • Islets of Langerhans Transplantation / physiology*
  • Male
  • Nerve Fibers / pathology
  • Neural Conduction
  • Nociceptors / physiology
  • Pain / physiopathology
  • Quality of Life
  • Rats
  • Rats, Inbred Lew
  • Sciatic Nerve / enzymology
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Tail / innervation
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Transplantation, Isogeneic

Substances

  • Blood Glucose
  • Thiobarbituric Acid Reactive Substances
  • Sodium-Potassium-Exchanging ATPase