Abstract
PURPOSE OF REVIEW: Pancreatic β-cells play a critical role in whole-body glucose homeostasis by regulating the release of insulin in response to minute by minute alterations in metabolic demand. As such, β-cells are staunchly resilient but there are circumstances where they can become functionally compromised or physically lost due to pathophysiological changes which culminate in overt hyperglycemia and diabetes. RECENT FINDINGS: In humans, β-cell mass appears to be largely defined in the postnatal period and this early replicative and generative phase is followed by a refractory state which persists throughout life. Despite this, efforts to identify physiological and pharmacological factors which might re-initiate β-cell replication (or cause the replenishment of β-cells by neogenesis or transdifferentiation) are beginning to bear fruit. Controlled manipulation of β-cell mass in humans still represents a holy grail for therapeutic intervention in diabetes, but progress is being made which may lead to ultimate success.