INS and Hypoinsulinemia: High-dose TCDD exposure in vivo caused persistent β-cell dysfunction in isolated islets (25, 86, 90), including diminished GSIS (25, 86, 90), impaired insulin secretion in response to a nonglucose secretagogue, α-ketoisocaproate (90), and decreased insulin content (86, 90); this aligns with the reported hypoinsulinemia in TCDD-exposed rodents (25, 29, 81, 83, 84, 86).