Revisiting Regulators of Human β-cell Mass to Achieve β-cell-centric Approach Toward Type 2 Diabetes

Hironobu Sasaki, Yoshifumi Saisho, Jun Inaishi, Hiroshi Itoh

Research output: Contribution to journalReview articlepeer-review

5 Citations (Scopus)


Type 2 diabetes (T2DM) is characterized by insulin resistance and β-cell dysfunction. Because patients with T2DM have inadequate β-cell mass (BCM) and β-cell dysfunction worsens glycemic control and makes treatment difficult, therapeutic strategies to preserve and restore BCM are needed. In rodent models, obesity increases BCM about 3-fold, but the increase in BCM in humans is limited. Besides, obesity-induced changes in BCM may show racial differences between East Asians and Caucasians. Recently, the developmental origins of health and disease hypothesis, which states that the risk of developing noncommunicable diseases including T2DM is influenced by the fetal environment, has been proposed. It is known in rodents that animals with low birthweight have reduced BCM through epigenetic modifications, making them more susceptible to diabetes in the future. Similarly, in humans, we revealed that individuals born with low birthweight have lower BCM in adulthood. Because β-cell replication is more frequently observed in the 5 years after birth, and β cells are found to be more plastic in that period, a history of childhood obesity increases BCM. BCM in patients with T2DM is reduced by 20% to 65% compared with that in individuals without T2DM. However, since BCM starts to decrease from the stage of borderline diabetes, early intervention is essential for β-cell protection. In this review, we summarize the current knowledge on regulatory factors of human BCM in health and diabetes and propose the β-cell-centric concept of diabetes to enhance a more pathophysiology-based treatment approach for T2DM.

Original languageEnglish
JournalJournal of the Endocrine Society
Issue number10
Publication statusPublished - 2021 Oct 1


  • beta-cell mass
  • beta-cell regulator
  • beta-cell workload
  • human pancreas
  • type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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