Research reportBlood glucose regulation mechanism in depressive disorder animal model during hyperglycemic states
Introduction
Depression not only affects brain and behavior but also affects the entire body. Depression has been associated with other health problems, including diabetes. Medically ill commonly shows depressive symptoms, although they are frequently unrecognized and untreated (Rodin and Voshart, 1986). A chronic medical condition such as diabetes mellitus could be associated with depressive syndromes (Pompili et al., 2009). Similarly, the presence of depressive symptoms makes the influenced individual more susceptible to become diabetic (Brownlee, 2008).
Stress is like the most significant health problem in modern life (Kudielka and Wust, 2010). Stress is an imbalance condition of homeostasis and results in various physiological and behavioral changes in the human body. Chronic stress may lead to depressive disorder (Raison et al., 2006). Repeated chronic stress, in general, promotes structural and functional alterations within the stress neurocircuitry system, and harmful effects on the regulation of a variety of brain functions (Gunn et al., 2011). Furthermore, stress stimulates the release of various stress-related hormones, and these effects can only endanger the brain. Stress hormones such as glucocorticoid and norepinephrine increase the blood glucose level (Surwit et al., 1992). Excessive exposure to stress-related hormones such as glucocorticoid can damage the brain and make the brain more vulnerable to normal neural damage (Sapolsky, 2000).
In general, during the stressful situations, the sympathetic nervous system (SNS) is activated, leading to a release of catecholamine from the adrenal medulla (Jansen et al., 1995). Catecholamines result in an increase of the blood glucose level by inhibiting insulin release and also stimulate the glycogenolysis (Ullrich and Wollheim, 1984). In addition, the hypothalamic-pituitary-adrenal (HPA) axis plays a major role in stress systems. The principal regulator of the HPA axis is a corticotrophin-releasing hormone (CRH). CRH is synthesized in the hypothalamus (Ito et al., 2005), and CRH stimulates the secretion of adrenocorticotropic hormone (ACTH) and subsequently, promotes glucocorticoid secretion from the adrenal cortex (Kalantaridou et al., 2010). It has been well demonstrated that glucocorticoid, in general, causes the hyperglycemia by activating a gluconeogenesis pathway (Fagerholm et al., 2011).
The stress-induced hyperglycemia effect has been well known for a long time (Mazzon and Cuzzocrea, 2008). Several lines of evidence have demonstrated that the chronic stress is closely associated with the pathogenesis of depression (Raison et al., 2006). Although the relationship between depression and the diabetes mellitus has been well known in some previous studies, the exact relationship of blood glucose regulation is chronic stress-induced depression has not been well characterized yet. Thus, the present study was designed to characterize the relationship between chronic stress-induced depression and blood glucose level in three hyperglycemic animal models in mice. First, we forced mice into chronic restraint stress for 2 h daily for two weeks to produce depression animal model. Then, we have characterized the possible role of the depression in the regulation of the blood glucose level in d-glucose-fed-, immobilization stress-, and clonidine-induced hyperglycemia animal model.
Section snippets
Materials and methods
All the experiments with animals were approved by the University of Hallym Animal Care and Use Committee (Registration Number: Hallym 2013-72). All procedures were conducted in accordance with the ‘Guide for Care and Use of Laboratory Animals' published by the National Institutes of Health.
Alterations of the blood glucose, corticosterone and insulin levels by depression in OGTT (oral glucose tolerance test) group
After all groups of mice had been fasted for 16 h, depressive mice were fed with d-glucose (2 g/kg) by oral administration. The blood glucose level was measured at 30, 60, 90, 120 and 180 min after the d-glucose feeding. As shown in Fig. 1A, the d-glucose feeding increased the blood glucose level. The blood glucose level reached at maximum 30 min (Mean ± SEM value at 30 min, Normal + Saline, 96 ± 11.3; Depression + saline, 72 ± 5.6, Normal + d-Glucose, 273.8 ± 20.45; Depression + d-Glucose, 206 ± 8.5) and returned to
Discussion
Depression treatment could improve glycemic control and health outcomes in patients with diabetes mellitus (Gendelman et al., 2009). There is a bidirectional association between depression and diabetes. The presence of diabetes doubles the chances of co-occurrence of depressive disorder (Pompili et al., 2009). Although the relationships of the depression with diabetes have been well known through some previous studies, the exact relationship of the blood glucose regulation and its mechanisms in
Conclusion
Our results suggest that the blood glucose level in the depression group is down-regulated as compared to the normal group during d-glucose-fed-, immobilization stress-, and clonidine-induced hyperglycemia in mice. Attenuation of plasma corticosterone level in the depression group might be responsible for the reduction of the blood glucose level in d-glucose-fed and acute immobilization stress mice model during the depression. Moreover, clonidine-induced corticosterone level was further
Declaration of Interest
The authors report no conflicts of interest.
Acknowledgements
This research was supported by Priority Research Centers (NRF-2009-0094071) Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology and Hallym University Fund. (HRF-201509-014)
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