Compensatory Lumbar Sympathetic Nerve Activation, Independent of Vagal Nerve Activity, Drives Hyperglycemia and Fat Utilization in STZ-Induced Acute Type 1 Diabetes

In the acute phase of streptozotocin (STZ)-induced type 1 diabetes, the mechanisms leading to hyperglycemia and a shift toward lipid-dominant metabolism remain unclear. We continuously recorded sympathetic and vagal nerve activity and metabolic parameters in freely moving rats to clarify how insulin deficiency alters substrate utilization and autonomic outflow. Male Wistar rats were chronically implanted with electrodes for cervical vagal nerve activity, renal and lumbar sympathetic nerve activity, arterial pressure telemetry, ECG, and an interstitial glucose sensor. Type 1 diabetes was induced by intraperitoneal STZ (65 mg/kg). STZ administration rapidly decreased plasma insulin, and interstitial glucose stabilized at ~320 mg/dl, producing marked hyperglycemia. The respiratory quotient decreased from ~0.9 to ~0.7, indicating near-complete loss of carbohydrate utilization and a compensatory increase in lipid oxidation. These metabolic changes reflect a forced shift to fat utilization due to impaired cellular glucose uptake caused by insulin deficiency. Continuous autonomic recordings revealed that lumbar sympathetic nerve activity increased persistently by >40%, whereas renal sympathetic nerve activity showed no significant change. Cervical vagal nerve activity exhibited only a transient and minimal response, indicating a lack of active vagal involvement. These findings demonstrate that hyperglycemia and lipid-dominant metabolism after STZ are driven not simply by insulin deficiency itself, but by a compensatory and sustained activation of lumbar sympathetic nerve activity, likely to mobilize alternative fuels. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.