Improved outcome of islet transplantation in insulin-treated diabetic mice: effects on beta-cell mass and function

Diabetologia. 1997 Sep;40(9):1004-10. doi: 10.1007/s001250050781.

Abstract

Insulin treatment may improve the outcome of islet transplantation. To determine the effects of insulin treatment on transplanted islets, 4 groups of streptozotocin-diabetic C57BL/6 mice were transplanted with 100 islets, an insufficient beta-cell mass to restore normoglycaemia. Groups 1 (n = 12) and 2 (n = 12), were kept normoglycaemic with insulin treatment from day 10 before transplantation to day 14 after transplantation; groups 3 (n = 12) and 4 (n = 18), were not treated with insulin. Grafts were harvested 14 (groups 1 and 3) or 60 (groups 2 and 4) days after transplantation and beta-cell mass and replication were measured. When insulin was discontinued all mice maintained normoglycaemia; in contrast, non-insulin-treated groups remained hyperglycaemic throughout the study. Fourteen days after transplantation the beta-cell mass was reduced both in group 1 (0.09 +/- 0.01 mg) and group 3 (0.14 +/- 0.02 mg) compared to the initially transplanted mass (0.22 +/- 0.02 mg, p < 0.01); beta-cell replication and area did not change in group 1, but were increased in group 3. Insulin content, expressed as a function of beta-cell mass, was maintained in group 1 grafts (12.5 +/- 2.0 micrograms/mg), but was severely reduced in group 3 (1.0 +/- 0.2 micrograms/mg) compared to non-transplanted islets (20.4 +/- 3.3 micrograms/mg). In group 2, beta-cell mass increased when insulin was discontinued; 60 days after transplantation beta-cell mass was similar to the initially transplanted mass (0.23 +/- 0.04 mg), glucose levels after an intraperitoneal glucose challenge were normal, and insulin content was preserved (19.6 +/- 2.7 micrograms/mg). In contrast, beta-cell mass was progressively reduced in group 4 (0.08 +/- 0.02 mg, p < 0.001). In summary, insulin treatment reduced the beta-cell mass needed to achieve normoglycaemia in islet transplantation. Islets transplanted to insulin-treated mice showed better beta-cell function, preserved insulin content, and were able to increase their beta-cell mass to meet an increased functional demand.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Size / drug effects
  • Cell Size / physiology
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / therapy*
  • Glucose Tolerance Test / methods
  • Hypoglycemic Agents / therapeutic use*
  • Injections, Intraperitoneal
  • Insulin / analysis
  • Insulin / therapeutic use*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / growth & development
  • Islets of Langerhans / physiology
  • Islets of Langerhans Transplantation*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Streptozocin
  • Treatment Outcome

Substances

  • Hypoglycemic Agents
  • Insulin
  • Streptozocin