IRS1 and Insulin resistance: Consistently, calculation of HOMA-IR (Fig. S3a, ESM), HOMA-B (Fig. S3b, ESM), QUICKI (Fig. S3c, ESM) and measurement of phosphorylated IRS-1 in liver lysates (Fig. S3d), showed that animals treated with STZ, either alone or in combination with CFTRinh172, displayed evidence of insulin resistance and poor insulin sensitivity.