Distinctions between the islets of mice and men: implications for new therapies for type 1 and 2 diabetes

Abstract

Objective: To elucidate why diabetes is so difficult to treat despite the present tools and pharmacologic armamentarium and to provide insights into emerging therapies by describing human and rodent data that demonstrates the ability to transform progenitor cells within the adult pancreas into new islets.

Methods: A literature review focused on the distinctions between human and rodent islets.

Results: We are beginning to elucidate important differences between the architecture and composition of the islets of Langerhans in humans and rodents. In contrast to rodent islets, human islets are more heterogeneous in cellular composition and have more prominent intra-islet vascularity, with smooth muscle-containing blood vessels that are not present in rodent islets. Some studies report that more than 70% of human beta cells have direct physical contact with other cell types, whereas others describe that smaller human islets possess features more typical of rodents, while larger islets exhibit greater vascularity and a cellular distribution distinct from centrally clustered beta cells surrounded by a mantle of alpha and delta cells found in rodents.

Conclusions: The differences between the islets of mice and men may influence why treatments hailed as reversing diabetes among rodents have not been successfully translated into humans. Increased understanding of the complexities within the human islet may yield unique insights into reversing diabetes in humans.