Introduction and Objective: Recurrent insulin-induced hypoglycemia blunts the counterregulatory response (CRR) to hypoglycemia. Since antecedent hyperinsulinemia coincides with antecedent hypoglycemia, it is possible that recurrent insulin administration per se could contribute to the pathophysiology of a blunted CRR. To target insulin delivery to the central nervous system, this study tested the hypothesis that recurrent intranasal insulin blunts the CRR to hypoglycemia.Methods: 8-10 week old male rats were randomly assigned to 3-days preconditioning. One group received recurrent intranasal insulin (RINI, 0.6U Humulin R) while a control group received recurrent intranasal saline (RINSAL). The dose of intranasal insulin was chosen to not lower systemic glucose levels. On day 4, all rats underwent a hyperinsulinemic (50mU/kg/min)-hypoglycemic (40-45 mg/dL) clamp to assess the CRR to hypoglycemia.Results: During hypoglycemia, the rats that underwent RINI had a significantly (*p<0.05) increased glucose infusion rate compared to controls indicating impaired counterregulation. Consistent with this observation, the RINI animals had a significantly (*p<0.05) blunted epinephrine response to hypoglycemia compared to RINSAL rats.Conclusion: In the absence of systemic glucose lowering effects, recurrent intranasal insulin preconditioning may act centrally to blunt the glucoregulatory and sympathoadrenal response to subsequent hypoglycemia.
Z. Beckner: None. M. Devore: None. L. Schoeder: None. J. Zohary: None. R. Zohary: None. W.H. Hall: None. S. Fisher: None.
NIDDK R01DK118082NIH T32DK138894
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