Islet Dimensions and Its Impact on the Cellular Composition and Insulin-Secreting Capacity: Insights Into the Role of Non-beta Cells.

Studies have underscored the significance of islet dimensions, encompassing i) the necessity for islets to maintain an optimal diameter to sustain functional activity; ii) larger islets exhibit an intermingled architecture of alpha and beta cells, enhancing functional activity through paracrine effects; iii) non-alpha/beta (NAB) cells play a significant role in regulating beta cells; and iv) there is a preferential loss of larger islets in cases of type 2 diabetes mellitus. To delve deeper into these aspects, the authors documented the cellular composition in islets of various dimensions and regions of the pancreas, along with their secreting capacity, using the expression of the myosin Va motor protein in nine non-diabetic adult human pancreases. The proportion of NAB cells was found to be higher in intermediate islets and significantly lower in smaller and larger islets. By comparing the differences in islet composition, where NAB cells increase from smaller to intermediate islets, leading to a decrease in the proportion of alpha and beta cells, and in larger islets, there is a higher proportion of beta and alpha cells similar to smaller islets, we propose the hypothesis that NAB cells proliferate as islets increase in size. Furthermore, in larger islets, these NAB cells convert into alpha and beta cells, resulting in the scattered, intermingled arrangement observed in larger islets. The higher intensity of myosin Va expression in the islets of the tail region, along with a similar proportion of NAB cells in intermediate islets of the tail region compared to larger islets, leads to decreased inhibitory stimuli to beta cells and an increased insulin-secreting capacity.