Abstract: | Aim The plasma concentration of vascular endothelial growth factor (VEGF) has recently been shown to increase sharply in response to hypoglycaemia and, thus, has been proposed as having a role in hypoglycaemia counter‐regulation. Many counter‐regulatory hormones show a reduced response after antecedent hypoglycaemia. We therefore investigated whether this decrease in responsiveness with repetitive hypoglycaemia also pertains to VEGF. Methods Three hypoglycaemic clamp experiments were performed on two consecutive days in 15 healthy men. VEGF response was assessed during the first and last hypoglycaemic period. Results As expected, plasma VEGF concentrations rose markedly during the clamps (P < 0.001). The increase was distinctly blunted during the third (+13 ± 8 pg/ml) as compared with the first (+54 ± 18 pg/ml) hypoglycaemic clamp (P = 0.046). Conclusion This data confirms that circulating VEGF concentrations increase acutely during hypoglycaemia. Like the counter‐regulatory hormones, the hypoglycaemia‐induced rise in VEGF is attenuated after antecedent hypoglycaemia. The origin of increased systemic VEGF concentration during hypoglycaemia and its physiological role remains to be defined. |