L. Jansson et al., IMPAIRMENT OF GLUCOSE-INDUCED INSULIN-SECRETION IN HUMAN PANCREATIC-ISLETS TRANSPLANTED TO DIABETIC NUDE-MICE, The Journal of clinical investigation, 96(2), 1995, pp. 721-726
Hyperglycemia-induced beta-cell dysfunction may be an important compon
ent in the pathogenesis of non-insulin-dependent diabetes mellitus. Ho
wever, most available data in this field were obtained from rodent isl
ets, To investigate the relevance of this hypothesis for human beta-ce
lls 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 perfusi
on, whereas grafts of hyperglycemic recipients failed to respond to gl
ucose, 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 ins
ulin content, but a decreased insulin response to glucose remained. No
ultrastructural signs of beta-cell damage were observed, with the exc
eption 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.