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To mitigate the chance of hypoglycaemia, we sought to improve GK action by blocking GKRP. Here we describe the identification of two powerful tiny-molecule GK–GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in numerous rodent models of diabetes. These compounds potently reversed the inhibitory result of GKRP on GK exe

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