Background: LKB1 regulates multiple aspects of pancreatic ß cell biology.

Results: LKB1 loss in ß cells leads to profound mitochondrial defects yet increases glucose-stimulated insulin secretion in a mitochondria-independent mechanism.

Conclusion: LKB1 is essential for mitochondrial maintenance and negatively regulates a distal step of insulin secretion.

Significance: LKB1 loss exposes powerful mechanisms of insulin secretion that can override defects in the classic triggering pathway.

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