The acute effects of l-Leucine and l-Isoleucine on glycemic responses in healthy and inactive adults

The ingestion of whey protein or insulinogenic amino acids (AA) with a CHO drink has been shown to blunt the elevated post-prandial glucose response. It has been suggested that AA may facilitate secretion of hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) that are 50-70% responsible for regulating insulin secretion. The purpose of this study was to examine the “priming” effect of pre-ingested L-Isoleucine (ISO) and L-Leucine (LEU) on glucose metabolism and glycemic hormones in healthy, inactive adults. We hypothesized that preingested ISO and LEU would diminish the post prandial rise in glucose prior to a 75 g oral glucose tolerance test (OGTT) and have minimal effect on enteroendocrine hormone secretion. To test this, 12 healthy adults (Females: n = 6, males: n = 6, Age 27.39 ± 2.05 year; height 167.42 ± 2.23 cm; weight 77.77 ± 3.73 kg; BMI 26.30 ± 2.14 kg/m2; lean bodymass [LBM] 53.20 ± 4.67 kg; body fat 34.14 ± 2.96%; fasting blood glucose [FBG] 89.5 ± 4.67 mg/dl) completed four trials in a randomized, single-blinded fashion. Each trial consisted of ingestion of either ISO + LEU in combination (50:50), ISO, LEU, or placebo (PLA). Each treatment was ingested 30 min prior to a 2 hr 75 g (GLU) OGTT. The amino acid drink (200 mL) was prepared based on the participant’s LBM at a standardized dose (0.3g/kg), while the PLA dose was 3.54 g. Blood samples were collected at baseline (0), followed by AA or PLA drink, 6, 10, 30, followed by GLU drink, 36, 40, 60, 90, 120, and 150 min with appropriate inhibitors used for valid quantification. Results show that Δ area of glucose analysis ISO+LEU, ISO, and LEU reduced glucose response more than PLA (p = .005); ISO + LEU and ISO lowered blood glucose at 60 min and 90 min ( p = < .05) compared to PLA. There was no difference between treatments in the AUC insulin concentration from baseline (p = .053); Δ change of C-peptide concentration was greater in ISO than PLA (p = .04), AUC differences showed ISO+LEU > PLA; the Δ change glucagon analysis showed no difference (p = .12); Δ change of GLP-1Active analysis showed no difference (P = .12); Δ change GIPTotal analysis ISO > LEU and PLA (p = .04). It appears that ISO and LEU combined or independently diminish glucose responses at peak time and ISO stimulates GIP and C-peptide concentrations more so than does LEU, and ISO and LEU have a negligible impact on GLP-1.