Correlation of insulitis progression with alpha-cell remodeling in individual islets in diabetic NOD mice.

<p>Composition of the insulitic lesion in 4-wk old diabetes-prone (islets from 5 mice), 12-wk old insulitic (islets from 7 mice) and 18–24 wk old diabetic (islets from 7 mice) female NOD mice (A, Insulitis score: white = 0 (pre-inflammation), lightest grey = 1 (less than 1/3 of the islet infiltrated), light grey = 2 (between 1/3 and 2/3 of the islet infiltrated), grey = 3 (more than 2/3 of the islet infiltrated), dark grey = 4 (islets with full insulitis) and black = 0 (post-inflammation)). Correlation between the severity of insulitis and degree of glucagon-positive alpha-cells in 4 wk old (diamond), 12 wk old (square) and 20 wk old diabetic NOD mice (triangle; B). Linear regression analysis revealed a negative correlation between the glucagon and insulitis score in the 12 wk old (dotted line R² = 0.79 and p<0.0005) and 20 wk old diabetic (solid line; R² = 0.85 and p<0.0001) groups. Note: islets with an insulitis score of zero may be either pre- or post-inflammation. Islets that were termed “post-inflammation” were easily identifiable; that is, the insulitis had dissipated following destruction of the beta-cells and largely been replaced by alpha and delta-cells.