Impairment of glucose-induced insulin secretion in human pancreatic islets transplanted to diabetic nude mice

J Clin Invest. 1995 Aug;96(2):721-6. doi: 10.1172/JCI118115.


Hyperglycemia-induced beta-cell dysfunction may be an important component in the pathogenesis of non-insulin-dependent diabetes mellitus. However, most available data in this field were obtained from rodent islets. To investigate the relevance of this hypothesis for human beta-cells in vivo, human pancreatic islets were transplanted under the renal capsule of nude mice. Experimental groups were chosen so that grafted islets were exposed to either hyper- or normoglycemia or combinations of these for 4 or 6 wk. Grafts of normoglycemic recipients responded with an increased insulin release to a glucose stimulus during perfusion, whereas grafts of hyperglycemic recipients failed to respond to glucose. The insulin content of the grafts in the latter groups was only 10% of those observed in controls. Recipients initially hyperglycemic (4 wk), followed by 2 wk of normoglycemia regained a normal graft insulin content, but a decreased insulin response to glucose remained. No ultrastructural signs of beta-cell damage were observed, with the exception of increased glycogen deposits in animals hyperglycemic at the time of killing. It is concluded that prolonged exposure to a diabetic environment induces a long-term secretory defect in human beta-cells, which is not dependent on the size of the islet insulin stores.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alloxan
  • Animals
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetes Mellitus, Type 2 / etiology*
  • Glucose / pharmacology*
  • Humans
  • Hyperglycemia / complications*
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / ultrastructure
  • Islets of Langerhans Transplantation* / pathology
  • Kidney
  • Mice
  • Mice, Nude
  • Middle Aged
  • Spleen
  • Transplantation, Heterologous
  • Transplantation, Heterotopic


  • Insulin
  • Alloxan
  • Glucose