Proposed model for mechanisms regulating β-cell mass in type 2 diabetes. Before onset of diabetes, insulin resistance may
lead to transient postprandial hyperglycemic excursions. Other factors modulating β-cell mass may include dyslipidemia, leptin,
and cytokines. Genetic predisposition to diabetes may include a predetermined amount of β-cell mass, as well as differences
in the susceptibility to apoptotic signals and in the regenerative potential of the β-cell. Additionally, induction of local
inflammatory mediators and cell death may activate the acquired immune system. Finally, drugs may protect or harm the β-cell.
GLP1, glucagon-like peptide 1; IRS-2, insulin receptor substrate 2; TNFα, tumor necrosis factor-α.