Older mice with a β-cell-specific loss of sirtuin 4 (SIRT4) have normal glucose-stimulated insulin secretion. Two-month-old male mice were treated with tamoxifen, and then experiments were performed 10 mo later. A: mice were weighed and then given an oral gavage of 1.5 mg/g glucose after a 6-h fast. B–E: blood glucose (B and C) and plasma insulin (D and E) levels were measured at the indicated time points postgavage. One week later, the same mice were gavaged with 0.3 mg/g l-leucine after a 6-h fast. F–I: blood glucose (F and G) and plasma insulin (H and I) levels were measured at the indicated time points postgavage. Data are average ± SE; n = 9 SIRT4+/+;MIP-Cre (tamoxifen-inducible Cre driven by the mouse insulin promoter)−, 10 SIRT4+/+;MIP-Cre+, 7 SIRT4flox/flox;MIP-Cre−, and 14 SIRT4flox/flox;MIP-Cre+ mice.