Summary
We studied the effect of chronic exposure to high glucose on the glucose transport regulation in hamster pancreatic Beta cells in permanent culture (HIT). Cells were exposed to either 5.5 mmol/l or 16.7 mmol/l glucose for 48 h and then glucose transport was studied by measuring the (3H)-2-deoxyglucose uptake for 5 and 10 min at 37 °C. The 2- deoxyglucose uptake was lower in cells pre-exposed to glucose 16.7 mmol/l for 48 h compared to cells pre-exposed to glucose 5.5 (12.0±1.6 vs 19.1±1.2 nmol/0.1 mg after 5 min, and 22.2±2.6 vs 39.0±2.9 after 10 min respectively, mean ±SEM, n=5, p < 0.01). In order to investigate the mechanism(s) for glucose impairment of glucose transport, we studied the glucose carrier gene expression in the same cells by Northern and slot-blot analysis. When total RNA was extracted from HIT cells cultured at either 5.5 or 16.7 mmol/l glucose and then hybridized to 32P-labelled cDNA probes for the glucose transporter 1, the glucose transporter 2 and β-actin, a significant reduction of both glucose transporter 1 (−63.9±4.1%, mean±SEM, n=3) and glucose transporter 2 (−48.9±3.2%) mRNA was observed in HIT cells cultured with high glucose. In the same experiments no change of β-actin mRNA was observed, suggesting that the effect of high glucose was specific on the glucose-transporter mRNAs. In HIT cells cultured at glucose 16.7 mmol/l the glucose-induced insulin release was also reduced compared to cells cultured at glucose 5.5 (715±19 μU · h−1 · mg−1 vs 1301±28 μU · h−1 · mg−1, respectively, mean ±SEM, n=3, p < 0.05). In conclusion, in hamster pancreatic Beta-cells, chronic exposure to high glucose concentrations impairs glucose transporter mRNA levels, glucose transport, and glucose-induced insulin secretion in a co-ordinate manner.
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Note: After this paper was submitted we became aware of two recent publications [9, 10] showing in animal models of non-insulin-dependent diabetes a decreased expression of the Beta-cell glucose transporter in pancreatic islets unresponsive to glucose, further supporting the view that this transporter may play a role in the glucosesensing mechanism.
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Purrello, F., Buscema, M., Vetri, M. et al. Glucose regulates both glucose transport and the glucose transporter gene expression in a hamster-derived pancreatic Beta-cell line (HIT). Diabetologia 34, 366–369 (1991). https://doi.org/10.1007/BF00405011
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DOI: https://doi.org/10.1007/BF00405011