Thrombin, but not PC activation, is enhanced in diabetic FVL mice and low-concentration thrombin protects glucose-stressed human podocytes. (A) In vivo aPC formation did not differ in diabetic FVwt, diabetic FVLr/q, or diabetic FVLq/q mice; n ≥ 7 for each group. (B) TAT levels in nondiabetic control mice or mice with long-term (26 weeks) hyperglycemia. Hyperglycemia increased TAT levels in wild-type (FVwt) and to a larger extent in heterozygous (FVLr/q) or homozygous (FVLq/q) FVL mice (n ≥ 10 for each group). (C-D) Apoptosis (green, TUNEL-positive) in cultured human podocytes exposed to glucose in the presence or absence of aPC (20nM) or thrombin (range, 5-20 nM). Representative images (C) with fluorescent-labeled nucleotides (green, TUNEL-positive) and Hoechst 33258 nuclear counter stain (blue) and bar graph (D) summarizing results of at least 3 independent experiments performed in duplicate; means ± SEM are shown. C indicates nondiabetic, control mice (white bars); DM, diabetic mice (black bars); *P < .05; **P < .01 (ANOVA).