ABCC8 Antibody

Introduction to ABCC8 and Its Antibody

ABCC8 encodes SUR1, a 1581-amino-acid transmembrane protein with 17 transmembrane domains . It modulates KATP channel activity, linking cellular metabolic state to insulin release . Mutations in ABCC8 cause dysregulated insulin secretion, leading to disorders such as CHI and neonatal diabetes . ABCC8 antibodies enable detection of SUR1 expression, aiding in mechanistic studies and therapeutic development.

3.1. Disease Modeling

• Congenital Hyperinsulinism: ABCC8 antibodies validated SUR1 loss in CRISPR/Cas9-generated ABCC8-deficient β-cells, which exhibited 2× higher insulin secretion vs. wild-type . These cells responded to diazoxide and glimepiride, confirming functional KATP channel disruption .

• Monogenic Diabetes: In a 35-year-old patient with ABCC8 mutation (c.3067C>T), antibodies confirmed SUR1 expression, guiding transition from insulin to sulfonylurea therapy .

3.2. Drug Screening

ABCC8 antibodies facilitated testing of nicorandil and nifedipine in ABCC8-deficient cells, showing 30–50% reduction in insulin secretion .

3.3. Genetic Variant Characterization

Minigene assays combined with antibody validation revealed splicing defects in 13 ABCC8 variants, reclassifying 7 as pathogenic . For example, rs757110 SNP increased exon skipping, suggesting a modifier role in CHI .

4.1. Neonatal Diabetes Management

Two infants with transient neonatal diabetes due to ABCC8 c.3880C>T variant showed undetectable SUR1 via antibody staining, enabling successful sulfonylurea therapy . Insulin secretion normalized within 1–12 months, avoiding long-term insulin use .

4.2. Functional Rescue in Hyperinsulinism

ABCC8−/− β-cells treated with octreotide showed 50% lower insulin secretion, validated via C-peptide and SUR1 Western blotting .

Challenges and Future Directions

• Specificity: Cross-reactivity with ABCC9 (SUR2) necessitates rigorous validation .

• Splicing Variants: 15% of ABCC8 variants alter splicing, requiring combined RNA/protein assays .

• Cost: Antibodies like SAB2100012 cost >$500/100 μL, limiting accessibility .