The aim of this study was to evaluate the effects of long term in vitro exposure of human pancreatic islets to different secretagogues on their subsequent secretory activity. Therefore, groups of 100 islets were cultured for 48 h in standard tissue culture medium (CMRL 1066) in the presence of 1 of the following: 5.5 mmol/L glucose, 16.7 mmol/L glucose, 5.5 mmol/ L glucose plus 10 mmol/L L-arginine, or 5.5 mmol/L glucose plus 100 μmol/L tolbutamide. Insulin levels in the culture medium declined with time under all culture conditions. Islets were then perifused and acutely stimulated with glucose (16.7 mmol/ L), L-arginine (10 mmol/L), and tolbutamide (100 μmol/L). Islets cultured in 16.7 mmol/L glucose showed no response to 16.7 mmol/L glucose [net area under the curve (Δ AUC), 11% of control], and a reduced response to acute tolbutamide (Δ AUC, 35% of control), but responded to L-arginine (Δ AUC, 75% of control). Islets cultured in the presence of 10 mmol/L L-arginine had reduced responses to glucose (Δ AUC, 11% of control) and tolbutamide (Δ AUC, 27% of control), but responded to L-arginine (Δ AUC, 75% of control). Islets cultured in tolbutamide did not respond to tolbutamide (Δ AUC, 14% of control) and showed a reduced responses to acute glucose (Δ AUC, 36% of control) and L-arginine (Δ AUC, 24% of control). In a second set of experiments, islets cultured in 5.5 or 16.7 mmol/L glucose showed an insulin response to a supramaximal glucose stimulation (30 mmol/L glucose plus 0.5 mmol/L isobutylmethylxanthine) that was not statistically different. Similarly, islets that were cultured in the presence of 100 μmol/L tolbutamide still responded to 1 mmol/L tolbutamide. In conclusion, all stimuli evaluated in this study, chronically applied, reduced the insulin response to further acute stimulations. The different patterns of unresponsiveness observed together with the finding of a preserved insulin content in the islets after perifusions and a maintained capability to release insulin in response to supramaximal stimulations suggest that after chronic exposure to different stimuli, human islets become selectively desensitized to the same stimuli given acutely and do not become exhausted.
|Number of pages||5|
|Journal||Journal of Clinical Endocrinology and Metabolism|
|Publication status||Published - Apr 1992|
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism