Branched-chain α-keto acids impair glucose-stimulated insulin secretion in pancreatic β-cells under diabetes by reactivating the LDHA-lactate axis - PubMed
12 hours ago
- #diabetes
- #insulin secretion
- #metabolism
- Branched-chain α-keto acids (BCKAs) impair glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells under diabetes.
- BCKAs redirect glucose metabolism from the TCA cycle to the LDHA-lactate axis, reactivating lactate dehydrogenase A (LDHA).
- Elevated BCKAs in diabetic humans negatively correlate with insulin secretory ability.
- Reducing BCKA levels improves glucose tolerance and GSIS in diabetic mice.
- BCKA directly binds to LDHA, promoting its dimerization and enhancing enzymatic activity.
- β-cell-specific LDHA ablation restores GSIS and glucose tolerance in BCKA-fed mice.
- The study links aberrant BCAA metabolism to β-cell dysfunction in diabetes.