Background Altered function of the hypothalamic–pituitary–adrenal (HPA) axis in type 2 diabetic patients, a condition preceded by pre-diabetes, has been shown to increase the risk of depression as well as cause downstream effects resulting in upregulation of gluconeogenesis and dyslipidemia. In addition, stress, either psychological from managing diabetes or lifestyle related, further activates the HPA axis causing an exaggerated stress response. This study investigated the activity of the HPA axis in selected markers of glucose handling, and the stress response relative to components of the HPA axis in a diet-induced pre-diabetic rat model. Methods Sprague Dawley Rats were randomly divided into non-pre-diabetic group (NPD) and pre-diabetic group (PD) (n = 6, per group) over a 20-week induction period and a further 12-week experimental period to get 32 weeks. At the end of the 20 and 32-week periods, glucose handling using the Homeostasis Model Assessment indices, adrenocorticotropic (ACTH) and corticosterone (CORT) concentrations were measured. Stress was induced and the forced swim test were performed in the 12-week experimental week. At the end of 32 weeks glucocorticoid and mineralocorticoid hippocampal receptors were also measured. Results Impaired glucose handling in the PD group as well as increase in corticosterone was observed at the end of both 20 and 32-week periods by comparison to NPD groups. No changes were observed in ACTH concentration at week 20 while, at week 32, a decrease in plasma ACTH concentration was observed in the PD group by comparison to the NPD group. The stressed-induced animals were stressed using the forced swim test: the behaviour observed showed an increase in immobility time in the PD stressed group by comparison to the NPD group. This was followed by the observation of a decrease in ACTH and CORT concentration in the PD stressed group by comparison to the NPD stressed group. Mineralocorticoid and glucocorticoid receptors gene expression were elevated in the stressed PD group relative to the stressed NPD group. Conclusion These observations, together, suggest that diet-induced pre-diabetes is associated with impaired HPA axis activity and deteriorating response to stress.
Aims/Introduction Derangements often observed with type 2 diabetes are associated with disturbances in renin–angiotensin–aldosterone system (RAAS) activity. A positive correlation between local RAAS activity and the complications observed in type 2 diabetes has been noted. However, the detrimental ramifications due to moderate hyperglycemia noted in prediabetes, and the affected organ system and mechanistic pathways are not elucidated. Hence, this study investigated the effects of diet‐induced prediabetes on RAAS in various organs. Materials and Methods Male Sprague–Dawley rats were separated into two groups: (i) non‐prediabetes through exposure to standard rat chow group; and (ii) diet‐induced prediabetes group by exposure to a high‐fat high‐carbohydrate diet for 32 weeks. RAAS activity in the skeletal muscle, adipose tissue, liver, pancreas and heart was determined through the analysis of RAAS components, such as renin, angiotensinogen, angiotensin‐converting enzyme and angiotensin II type 1 receptor through polymerase chain reaction, as well as the quantification of angiotensin II and aldosterone concentration. Furthermore, nicotinamide adenine dinucleotide phosphate oxidase, superoxide dismutase and glutathione peroxidase 1 concentrations were determined in the skeletal muscle, pancreas and heart, in addition to the hepatic triglycerides. Results The RAAS components were elevated in the diet‐induced prediabetes group when compared with the non‐prediabetes group. This was further accompanied by increased nicotinamide adenine dinucleotide phosphate oxidase and reduced superoxide dismutase and glutathione peroxidase 1 concentrations in the selected organs, in addition to the elevated hepatic triglycerides concentration in the diet‐induced prediabetes by comparison to non‐prediabetes group. Conclusions Due to these observed changes, we suggest that local RAAS activity in the prediabetes state in selected organs elicits the derangements noted in type 2 diabetes.
Background: Altered function of the hypothalamic-pituitary-adrenal (HPA) axis in type 2 diabetic patients, a condition preceded by pre-diabetes, has been shown to increase the risk of depression as well as cause downstream effects resulting in upregulation of gluconeogenesis and dyslipidemia. In addition, stress, either psychological from managing diabetes or lifestyle related, further activates the HPA axis causing an exaggerated stress response. This study investigated the activity of the HPA axis in selected markers of glucose handling, and the stress response relative to components of the HPA axis in a diet-induced pre-diabetic rat model. Methods: Sprague Dawley Rats were randomly divided into non-prediabetic group (NPD) and pre-diabetic group (PD) (n=6, per group) over a 20-week induction period and a further 12-week experimental period to get 32 weeks. At the end of the 20 and 32-week periods, glucose handling using the Homeostasis Model Assessment indices, adrenocorticotropic (ACTH) and corticosterone (CORT) concentrations were measured. Stress was induced and the forced swim test (FST) were performed in the 12-week experimental week. At the end of 32 weeks glucocorticoid and mineralocorticoid hippocampal receptors were measured too. Results: Impaired glucose handling in the PD group as well as increase in corticosterone (CORT) was observed at the end of both 20 and 32-week periods by comparison to NPD groups. No changes were observed in ACTH concentration at week 20 while, at week 32, a decrease in plasma ACTH concentration was observed in the PD group by comparison to the NPD group. The stressed-induced animals were stressed underwent the forced swim test: the behaviour observed showed an increase in immobility time in the PD stressed group by comparison to the NPD group. This was followed by the observation of a decrease in ACTH and CORT concentration in the PD stressed group by comparison to the NPD stressed group. Mineralocorticoid and glucocorticoid receptors gene expression were elevated in the stressed PD group relative to the stressed NPD group. Conclusion: These observations, together, suggest that diet-induced pre-diabetes is associated with impaired HPA axis activity and deteriorating response to stress.
Background: Altered function of the hypothalamic-pituitary-adrenal (HPA) axis in type 2 diabetic patients, a condition preceded by pre-diabetes, has been shown to increase the risk of depression as well as cause downstream effects resulting in upregulation of gluconeogenesis and dyslipidemia. In addition, stress, either psychological from managing diabetes or lifestyle related, further activates the HPA axis causing an exaggerated stress response. This study investigated the activity of the HPA axis in selected markers of glucose handling, and the stress response relative to components of the HPA axis in a diet-induced pre-diabetic rat model. Methods: Sprague Dawley Rats were randomly divided into non-prediabetic group (NPD) and pre-diabetic group (PD) (n=6, per group) over a 20-week induction period and a further 12-week experimental period to get 32 weeks. At the end of the 20 and 32-week periods, insulin resistance using the HOMA-IR index, adrenocorticotropic (ACTH) and corticosterone (CORT) concentrations were measured. Stress was induced and the forced swim test (FST) were performed in the 12-week experimental week. At the end of 32 weeks glucocorticoid and mineralocorticoid hippocampal receptors were measured too. Results: Impaired glucose handling in the PD group as well as increase in corticosterone (CORT) was observed at the end of both 20 and 32-week periods by comparison to NPD groups. No changes were observed in ACTH concentration at week 20 while, at week 32, a decrease in plasma ACTH concentration was observed in the PD group by comparison to the NPD group. The stressed-induced animals were stressed underwent the forced swim test: the behaviour observed showed an increase in immobility time in the PD stressed group by comparison to the NPD group. This was followed by the observation of a decrease in ACTH and CORT concentration in the PD stressed group by comparison to the NPD stressed group. Mineralocorticoid and glucocorticoid receptors gene expression were elevated in the stressed PD group relative to the stressed NPD group. Conclusion: These observations, together, suggest that diet-induced pre-diabetes is associated with impaired HPA axis activity and deteriorating response to stress.
The activity of the renin-angiotensin-aldosterone system (RAAS) in type2 diabetes (T2D) has been characterized. However, the effects of high-fat high carbohydrate diet-induced prediabetes on the RAAS has not been elucidated. Hence, male Sprague Dawley rats were randomly assigned to a normal diet (NPD) group and (HFHC) group (n=6) for 20 weeks to allow for the induction of prediabetes. Blood glucose concentration, mean arterial pressure (MAP), kidney renin, angiotensinogen, angiotensin-converting enzyme (ACE), angiotensin II type 1a receptor (Agtr1a) in addition to kidney and plasma angiotensin II (Ang II), aldosterone were analyzed at week 20 to investigate the RAAS activity. In addition to kidney injury marker (Kim1) and urinary protein, concentrations were analyzed at week 20. The results demonstrated an increase in blood glucose, MAP, relative expression of kidney RAAS components in the HFHC group by comparison to the NPD. Furthermore, an increase in plasma Ang II and aldosterone was accompanied by elevated Kim-1 and albumin excretion in the HFHC diet group by comparison to the NPD group. Thus, we suggest that the RAAS is activated in diet-induced prediabetes and may induce early kidney damage.
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