Therapeutic Strategies Targeting Pancreatic Islet β-Cell Proliferation, Regeneration, and Replacement

• Published in: Endocrinology (Philadelphia) Vol. 164; no. 1
• Main Authors: Goode, Roy A, Hum, Julia M, Kalwat, Michael A
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 14.11.2022
• Subjects: Beta cells; Cell cycle; Cell Differentiation; Cell Proliferation; Clinical trials; Diabetes mellitus; Diabetes Mellitus - metabolism; Diabetes Mellitus - therapy; Differentiation (biology); Endocrinology; High-throughput screening; Humans; Insulin; Insulin - metabolism; Insulin-Secreting Cells - metabolism; Mini-Review; Pancreas; Pluripotency; Regeneration; Regeneration - physiology; Stem cells; Therapeutic targets; pancreatic islet beta cells; induced pluripotent stem cells; proliferation; diabetes
• ISSN: 1945-7170; 0013-7227; 1945-7170
• DOI: 10.1210/endocr/bqac193

Diabetes results from insufficient insulin production by pancreatic islet β-cells or a loss of β-cells themselves. Restoration of regulated insulin production is a predominant goal of translational diabetes research. Here, we provide a brief overview of recent advances in the fields of β-cell proliferation, regeneration, and replacement. The discovery of therapeutic targets and associated small molecules has been enabled by improved understanding of β-cell development and cell cycle regulation, as well as advanced high-throughput screening methodologies. Important findings in β-cell transdifferentiation, neogenesis, and stem cell differentiation have nucleated multiple promising therapeutic strategies. In particular, clinical trials are underway using in vitro-generated β-like cells from human pluripotent stem cells. Significant challenges remain for each of these strategies, but continued support for efforts in these research areas will be critical for the generation of distinct diabetes therapies.