Glucagon counterregulation (GCR) is a key protection against hypoglycemia which is compromised in diabetes via an unknown mechanism. To test the hypothesis that -cell inhibiting signals that are switched-off during hypoglycemia amplify GCR we studied STZ-treated male Wistar rats and estimated the effect on GCR of intrapancreatic infusion and termination during hypoglycemia of saline, insulin, and somatostatin. Times 10 min before and the 45 min after the switch-off were analyzed. Insulin and somatostatin, but not saline, switch-off significantly increased the glucagon levels (p=0.03) and the fold increases relative to baseline were significantly higher (p<0.05) in the insulin and somatostatin vs. the saline group. The peak concentrations were also higher in the insulin (184 pg/mL) and somatostatin (116 pg/mL) vs. the saline (58 pg/mL) group (p<0.05). GCR was pulsatile in most animals indicating a feedback regulation. After the switch-off, the number of secretory events and the total pulsatile production were lower in the saline vs. the insulin or somatostatin groups (p<0.05) indicating enhancement of glucagon pulsatile activity by insulin and somatostatin as compared to saline. Network modeling analysis demonstrates that reciprocal interactions between - and -cells can explain the amplification by interpreting the GCR as a rebound response to the switch-off. The model justifies experimental designs to further study the intrapancreatic network in relation to the switch-off phenomenon. The results of this proof-of-concept interdisciplinary study support the hypothesis that GCR develops as a rebound pulsatile response of the intrapancreatic endocrine feedback network to switch-off of -cell inhibiting islet signals.