Figure 1.

Homeostatic control of β-cell mass in rodents and humans. (a) Control of β-cell mass (the fulcrum of the balance) is based on the relative contribution of processes that result in β-cell gain (replication, hypertrophy, neogenesis) and β-cell loss (death, atrophy, autophagy). A net increase in β-cell mass occurs when mechanisms involved in β-cell gain exceed those of β-cell loss. Improper regulation of this balance is a major contributor to the onset of diabetes. (b) Experimental evidence in rodents and humans of β-cell gain mechanisms (β-cell replication, hypertrophy and neogenesis) during adaptive increases in β-cell mass in response to various increases in metabolic loads (neonatal period, pregnancy, obesity and β-cell recovery after injury). Dark square, evidence for β-cell gain mechanism only in rodent models; white square, only in human autopsy pancreatic samples; striped square, evidence both in rodents and humans; question mark square, no current evidence. This highlights the plasticity of the β-cell’s ability to increase its mass during different physiological and pathological (hyperglycemic) states and the relatively large amount of knowledge that remains to be uncovered, especially with respect to human β-cell biology.