Insulin Regulation of Sugar Transport in Isolated Pancreatic Acini from Diabetic Mice

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Abstract
Insulin-stimulated sugar transport was studied in isolated pancreatic acini prepared from streptozotocintreated mice. In this tissue, insulin increased the uptake of two nonmetabolized D-glucose analogues, [3H] 2-deoxy-D-glucose (2DG), and [3H]3-O-methyl-D-glucose (30MG), but had no effect on the uptake of [3H] L-glucose. A significant effect of insulin on 2DG uptake was seen at 100 pM, whereas a maximal effect required a concentration of 100 nM. The action of insulin on 2DG uptake was time-dependent; 90 min was required for a maximal hormonal effect. This increase in 2DG uptake was due to a greater than twofold increase in the maximal rate of uptake (Vmax); no significant effects were seen on Km. The mode of insulin action on sugar transport was investigated further. In pancreatic acinar cells, insulin did not alter either membrane potential or 45Ca2+ efflux, two proposed mechanisms for regulation of sugar transport in other tissues. The action of insulin was not due to either contamination with cholecystokinin (CCK) or an action via the CCK receptor. CCK is known to stimulate sugar transport in isolated pancreatic acini via the elevation of intracellular Ca2+. The effect of insulin on 2DG uptake, however, was additive to that of CCK; conversely, dibutyryl cyclic GMP, a known competitive antagonist of CCK, had no effect on insulin stimulation of 2DG uptake, insulin increased 2DG uptake in the presence of 10 μM puromycin, a concentration sufficient to inhibit greater than 90% of protein synthesis. Dihydrocytochalasin B, a compound known to alter acinar cell motility by disrupting microfilaments, progressively blocked insulin stimulation of 2DG uptake over a drug concentrationrange of 1–15 μg/ml These data suggest, therefore,that the time-dependent increase of sugar transport by insulin is unrelated to electrical potential, 45Ca2+ efflux, and new protein synthesis, but may result from a microfilament-related translocation of glucose carrier sites to the plasma membrane.

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