Several studies have convincingly shown that mature beta cells have the potential to proliferate. Recently, elegant experiments by Nir and colleagues showed that beta cells can also reproduce in a hyperglycaemic milieu. These investigators combined a transgenic mouse that expresses reverse tetracycline-dependent transactivator (rtTA) in beta cells with a strain that expresses a diphtheriatoxin-A subunit under an rtTA-responsive promoter. After doxycycline administration, rtTA induced expression of the diphtheria toxin, which caused apoptosis in 80% of beta cells, insulin deficiency, and hyperglycaemia. Doxycycline withdrawal was followed by spontaneous beta-cell regeneration with full recovery of insulin production, even when glucose concentrations were greater than 28 mmol/L This finding challenges the notion that glucotoxicity is a major hindrance to beta-cell proliferation and survival, and provides a new perspective on cell-based treatmentsthataimto harness beta-cell regenerative capacity and restore insulin production in patients with type 1 diabetes and autoimmune beta-cell disruption.
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