Continuous recording of cervical vagal and sympathetic nerve activity and heart rate during the onset of type 1 diabetes

Sympathetic nerve activity (SNA) and vagal nerve activity (VNA) play crucial roles in the homeostatic control of plasma glucose concentrations. However, the time course of changes in SNA and VNA during the onset of diabetes remains poorly understood. In this study, we induced type 1 diabetes using streptozotocin (STZ) and continuously monitored renal sympathetic nerve activity (RSNA), lumbar sympathetic nerve activity (LSNA), cervical VNA, heart rate, and heart rate variability before and after the onset of type 1 diabetes. [Methods] Male Wistar rats were chronically implanted with electrodes to measure electroencephalograms, electromyograms, electrocardiograms, RSNA, LSNA, and cervical VNA. Glucose sensors were used to monitor interstitial glucose concentrations. After a 5-day control period, STZ (65 mg/kg) was administered intraperitoneally to induce type 1 diabetes. All parameters were continuously recorded throughout the experiment. [Results] Following STZ administration, blood glucose concentrations rapidly increased within several hours, temporarily decreased, and then rose again, resulting in a sustained hyperglycemic state thereafter. Blood insulin concentrations showed changes mirroring those of blood glucose concentrations. Heart rate was the most sensitive parameter, with a gradual decline immediately after the onset of diabetes. LSNA significantly ( P <0.05) increased by approximately 40% from Day 1 onward compared with the control period. In contrast, cervical VNA, arterial pressure, and RSNA showed no significant changes after STZ administration. [Discussion] A major challenge of this study was the simultaneous and continuous monitoring of cervical vagal nerve activity, RSNA, and LSNA during the transition from a normal state to the onset of type 1 diabetes. The absence of significant changes in cervical VNA suggests that cervical VNA may not be involved in regulating blood glucose concentrations during the transition from normoglycemia to severe hyperglycemia (~350 mg/dL). Similarly, RSNA did not show any notable changes triggered by the onset of type 1 diabetes. However, the increase in LSNA with type 1 diabetes indicated an organ-specific sympathetic drive. These findings suggest that the persistent decline in heart rate after the onset of diabetes cannot be explained by changes in cervical VNA, RSNA, or LSNA. Based on these results, the following causal relationship is hypothesized to explain the decrease in HR and the increase in LSNA: the reduced insulin secretion caused by STZ leads to hyperglycemia, which is associated with decreased glucose availability as a substrate for energy production in muscle cells, including those of the heart. This reduction in energy supply likely contributes to the gradual decrease in HR. The increase in LSNA could be a compensatory mechanism to counteract the reduced glucose uptake by skeletal and cardiac muscles. Moreover, this heightened LSNA may help maintain systemic arterial pressure and ensure adequate tissue perfusion under conditions of impaired metabolic homeostasis caused by type 1 diabetes. JST (JPMJMS2023) This abstract was presented at the American Physiology Summit 2025 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.