Streptozotocin-induced type 1 and 2 diabetes in rodents: a model for studying diabetic cardiac autonomic neuropathy

Background: Several animal models are continually being developed to study diabetic complication. Several conflicting regimen for diabetes induction exist in the literature with varying dose strength and regimen for different study interest in diabetes. This study aims to show the effect of high dose streptozotocin (STZ) on the one hand compared with multiple low doses after high fat diet induction on diabetic cardiac autonomic neuropathy (DCAN). Methodology: Eighty-four Wistar rats were used to demonstrate DCAN induction using 2 approaches one for T1DM (STZ 50mg/kg) and the other for T2DM (HFD for 8 weeks with STZ 25mg/Kg daily for five days). DCAN features were assessed using invasive biomarkers, histology patterns and cardiac nerve densities. Results: Diabetes induction rate was 76% and 89% in T1DM and T2DM model respectively. T1DM group had significant weight loss, reduced c-peptide, and insulin level post induction. The T2DM additionally showed significantly higher total cholesterol and Homeostatic model assessment (HOMA) compared with control. Serum levels of catecholamine, choactase, nerve growth factor and cardiac nerve density confirms development of DCAN. Conclusion: High single dose of STZ and HFD with multiple low doses of STZ may be recommended for DCAN study in T1DM and T2DM rat model respectively. Keywords: Diabetic cardiac autonomic neuropathy; Diabetes mellitus; Heart rate variability; Streptozotocin.

Carvedilol improves heart rate variability indices, biomarkers but not cardiac nerve density in streptozotocin-induced T2DM model of diabetic cardiac autonomic neuropathy

Objectives There has been increasing recognition of the significant relationship between the autonomic nervous system and cardiovascular sequel in diabetes mellitus (DM) patients. Diabetic cardiac autonomic neuropathy (DCAN) still poses a treatment challenge in the clinical settings despite several research interventions. This study was designed to investigate the effect of carvedilol on experimentally induced DCAN in type 2 DM rat model. Methods DCAN was induced in 42 Wistar rats using high fat diet (HFD) for eight weeks, thereafter streptozotocin (STZ) at 25 mg/kg daily for five days. DCAN features were then assessed using non-invasive time and frequency varying holter electrocardiogram (ECG), invasive biomarkers, cardiac histology and cardiac nerve density. Results Carvedilol significantly ameliorated the effects of DCAN on noradrenaline (p=0.010) and advanced glycated end products (AGEs) (p<0.0001). Similarly, carvedilol reversed the reduction in levels of antioxidants, sorbitol dehydrogenase (SD) activity (p=0.009) nerve growth factors (p<0.0001) and choline acetyl-transferase (p=0.031) following DCAN induction. Furthermore, heart rate variability (HRV) indices which were also reduced with DCAN induction were also ameliorated by carvedilol. However, carvedilol had no significant effect on cardiac neuronal dystrophy and reduced cardiac nerve densities. Conclusions Carvedilol improves physiological HRV indices and biomarkers but not structural lesions. Early detection of DCAN and intervention with carvedilol may prevent progression of autonomic neurologic sequel.