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. 2023 Nov:249:103117.
doi: 10.1016/j.autneu.2023.103117. Epub 2023 Aug 23.

Spontaneous baroreflex sensitivity is attenuated in male UCD-type 2 diabetes mellitus rats: A link between metabolic and autonomic dysfunction

Milena Samora  1 , Yu Huo  1 , Richard K McCuller  1 , Suchit Chidurala  1 , Kimber L Stanhope  2 , Peter J Havel  2 , Audrey J Stone  1 , Michelle L Harrison  3
Affiliations

Spontaneous baroreflex sensitivity is attenuated in male UCD-type 2 diabetes mellitus rats: A link between metabolic and autonomic dysfunction

Milena Samora et al. Auton Neurosci. 2023 Nov.

Abstract

Patients with type 2 diabetes mellitus (T2DM) have impaired arterial baroreflex function, which may be linked to the co-existence of obesity. However, the role of obesity and its related metabolic impairments on baroreflex dysfunction in T2DM is unknown. This study aimed to investigate the role of visceral fat and adiponectin, the most abundant cytokine produced by adipocytes, on baroreflex dysfunction in T2DM rats. Experiments were performed in adult male UCD-T2DM rats assigned to the following experimental groups (n = 6 in each): prediabetic (Pre), diabetes-onset (T0), 4 weeks after onset (T4), and 12 weeks after onset (T12). Age-matched healthy Sprague-Dawley rats were used as controls. Rats were anesthetized and blood pressure was directly measured on a beat-to-beat basis to assess spontaneous baroreflex sensitivity (BRS) using the sequence technique. Dual-energy X-ray absorptiometry (DEXA) was used to assess body composition. Data are presented as mean ± SD. BRS was significantly lower in T2DM rats compared with controls at T0 (T2D: 3.7 ± 3.2 ms/mmHg vs Healthy: 16.1 ± 8.4 ms/mmHg; P = 0.01), but not at T12 (T2D: 13.4 ± 8.1 ms/mmHg vs Healthy: 9.2 ± 6.0 ms/mmHg; P = 0.16). T2DM rats had higher visceral fat mass, adiponectin, and insulin concentrations compared with control rats (all P < 0.01). Changes in adiponectin and insulin concentrations over the measured time-points mirrored one another and were opposite those of the BRS in T2DM rats. These findings demonstrate that obesity-related metabolic impairments may contribute to an attenuated spontaneous BRS in T2DM, suggesting a link between metabolic and autonomic dysfunction.

Keywords: Adiponectin; Baroreflex function; Insulin; Obesity; UCD-T2DM.

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Conflict of interest statement

Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.. Spontaneous baroreflex sensitivity in T2DM and age-matched healthy rats.
Values are presented as group averaged and individual data points. Data were compared using a two-way ANOVA with Sidak post hoc analysis for multiple comparisons and are expressed as means ± SD. Sample size is the same for every group (n=6). Pre, pre diabetic; T0, diabetes-onset; T4, 4 weeks after onset; T12, 12 weeks after onset. *P<0.05 vs. healthy within time-point. ‡P<0.05 vs. T0 within group.
Figure 2.
Figure 2.. Body composition in T2DM and age-matched healthy rats.
Values are presented as group averaged and individual data points. Both fat and lean mass were normalized to body weight. Data were compared using a two-way ANOVA with Sidak post hoc analysis for multiple comparisons when applicable and are expressed as means ± SD. Sample size is the same for every group (n=6). Pre, pre diabetic; T0, diabetes-onset; T4, 4 weeks after onset; T12, 12 weeks after onset. *P<0.05 vs. healthy within time-point. †P<0.05 vs. Pre within group. ‡P<0.05 vs. T0 within group. §P<0.05 vs. T4 within group.
Figure 3.
Figure 3.. DEXA scan images for a single representative healthy and T2DM rats.
Region of interest (ROI) from the whole-body scan extended from L3/L2 vertebral space to L5/L6 vertebral space with the lateral borders extending to the edge of the abdominal soft tissue (blue rectangle on the scans). Panel F shows the group averaged and individual data points for the percent of visceral fat in T2DM and healthy rats. Percent visceral fat is the ratio between fat mass and total tissue within the ROI. Data were compared using a two-way ANOVA and are expressed as means ± SD. Sample size is the same for every group (n=6). Pre, pre diabetic; T0, diabetes-onset; T4, 4 weeks after onset; T12, 12 weeks after onset.
Figure 4.
Figure 4.. Serum adiponectin (A) and insulin (B) concentrations in T2DM and age-matched healthy rats.
Values are presented as group averaged and individual data points. Data were compared using a two-way ANOVA and are expressed as means ± SD. Sample size is the same for every group (n=6), except one T2DM rat and one healthy rat from the T4 insulin groups that were considered outliers (i.e., values greater than 2.5 standard deviations from the mean) and were excluded. Pre, pre diabetic; T0, diabetes-onset; T4, 4 weeks after onset; T12, 12 weeks after onset.
See this image and copyright information in PMC

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