Insulinopenia and persistent hyperglycaemia was induced in experimental mice using low dose streptozotocin (STZ, 60 mg/kg, freshly dissolved in 0.05 M sterile sodium citrate, pH 4.5) on five successive days in 8-week-old mice as described5 (link),17 (link),19 . To study the consequences of insulin resistance db/db mice were used. For further details see supplementary information.
Subgroup of mice received various interventions. We intraperitoneally injected either tauroursodeoxycholic acid (TUDCA) (150 mg/kg bodyweight, dissolved in saline) or saline once daily starting 18 weeks after the last streptozotocin (STZ) injection until 1 d before analyses (week 26) in some mice5 (link). In other mice we intraperitoneally injected aPC (1 mg/kg bodyweight, every alternate day) or an equal volume of saline. Aditionally, in a subgroup of mice aPC was pre-incubated before injection with the HAPC1573 antibody at a 1:1 ratio for 10 min under gentle agitation to block its anticoagulant activity20 (link),21 (link). Human aPC was used throughout the study, which was generated following an established protocol22 (link).
Subgroup of mice received various interventions. We intraperitoneally injected either tauroursodeoxycholic acid (TUDCA) (150 mg/kg bodyweight, dissolved in saline) or saline once daily starting 18 weeks after the last streptozotocin (STZ) injection until 1 d before analyses (week 26) in some mice5 (link). In other mice we intraperitoneally injected aPC (1 mg/kg bodyweight, every alternate day) or an equal volume of saline. Aditionally, in a subgroup of mice aPC was pre-incubated before injection with the HAPC1573 antibody at a 1:1 ratio for 10 min under gentle agitation to block its anticoagulant activity20 (link),21 (link). Human aPC was used throughout the study, which was generated following an established protocol22 (link).
