Beta-cell failure in the pathogenesis of type 2 diabetes mellitus

Type 2 diabetes is the result of a progressive impairment of pancreatic β-cell function in the setting of worsening insulin resistance. Studies in high-risk populations have demonstrated that during progression to diabetes, β cells have declining function and lose the first phase of insulin secretion, resulting in less than adequate suppression of hepatic glucose production following meals. In addition, oscillations of insulin secretion become unmatched from their normal coupling with glucose. Several mechanisms are thought to be responsible for impaired β-cell function, including glucose toxicity and lipotoxicity, and potentially contribute to β-cell loss. Advances in molecular science have elucidated several cytokines and transcription factors possibly implicated in the loss of β-cell mass. In the past 15 years, clinical trials have given hope for potential therapies that may either delay or prevent the progression to diabetes. Lifestyle modification and pharmaceutical treatment remain the most promising interventions. Copyright © 2004 by Current Science Inc.