Enhancement of beta-cell sensitivity to glucose by oral fat load

Recent studies have demonstrated that 6 h infusions of lipid emulsion enhance insulin release, whereas 24 h infusions inhibit insulin secretion. How insulin release is modulated after oral fat loading has not yet been elucidated. 17 healthy fasting volunteers were subjected to 3 experiments in random order: test 1 was a frequently sampled i. v. glucose tolerance test (FSIVGTT, 0.3 g/kg glucose), test 2 began with the ingestion of 50 % sunflower oil (1.5 g/kg) followed by FSIVGTT 4 h later. Test 3 was identical to test 2 with i. v. addition of 100 U/kg heparin prior to FSIVGTT. Glucose and insulin data were analyzed by minimal model assumptions - glucose sensitivity of the beta-cells (Theta1), acute insulin response (AIR) (10 min), 3 h insulin release (Theta2), glucose threshold of insulin secretion (h), insulin degradation rate (n), peripheral insulin sensitivity (S(I)), and glucose-dependent glucose disposal (S(G)). After drinking the fat emulsion, FFAs increased to 0.8 +/- 0.3 mmol/l (test 2) and to 3.0 +/- 0.3 mmol/l (test 3). Moderately increased FFA concentrations were associated with elevation of Theta1 (test 1, control 335 +/- 157 vs. test 2: 859 +/- 612 pM x min x mM(-1), p = 0.030). At high plasma FFA levels and in the presence of heparin (test 3), Theta1 was reduced compared to test 2 and unchanged compared to test 1. Theta2 and h were elevated in both tests 2 and 3 compared to test 1. No changes of n, S(I) and S(G) were found. In conclusion, the ingestion of sunflower oil triglyceride emulsion resulted in a 60 % increase in plasma free fatty acids and enhanced the capacity of beta-cells to secrete insulin. Heparin-induced high levels of FFA further augmented the total insulin release and inhibited parameters of glucose responsiveness.