Translational research on human pancreatic β-cell mass expansion for the treatment of diabetes.

Abstract

The structural, functional, and pathological differences between human islets and rodent islets, such as mouse or rat islets, have been clarified, and research using human islets is becoming more important for elucidating the pathophysiology of diabetes and developing therapeutic strategies for diabetes. Increasing the functional human β-cell mass is a feasible method for the treatment of both type 1 and type 2 diabetes. The glucokinase-mediated glucose signaling pathway is known to promote β-cell proliferation not only in rodent models but also in humans. However, little is known about the signaling components of glucose- or glucokinase-mediated signaling pathways. Studies have gradually revealed the involvement of ER stress-related molecules, cell cycle regulators, inflammatory proteins, extracellular matrix proteins, and neurotransmitters in the glucokinase-mediated signaling pathway in β-cells. Unraveling the mechanisms of those molecules in the regulation of human β-cell mass will provide new insights into how the functional β-cell mass can be increased. The human islet distribution program is essential for human islet research. However, human islets for research are only available by import from Europe and America into Japan or Asia. Since Japanese or Asian diabetes patients possibly show different features compared with European or American diabetes patients, studies using human islets from Japanese or Asian populations have become important for the elucidation of pathophysiology in these specific population groups. This review outlines new pathways important for the regulation of human pancreatic β-cell mass and expectations regarding the establishment of a human islet distribution program in Japan.