Dietary iron supplements may affect stress adaptation and aggravate stress hyperglycemia in a rat model of psychological stress

Shen

et al. 2017

Sci Rep

Self Cite

Iron overload has attracted much attention because of its adverse effect in increasing the risk of developing several neurodegenerative disorders. Under various pathologic conditions, a lot of heme are released. The aggregation of heme is more neurotoxic than that of iron released from the heme breakdown. Our previous studies demonstrated that psychological stress (PS) is a risk factor of cerebral iron metabolism disorders, thus causing iron accumulation in rat brains. In the present study, we found PS could increase heme uptake via heme carrier protein 1 (HCP1) in rat brains. We demonstrated that Glucocorticoid (GC), which is largely secreted under stress, could up-regulate HCP1 expression, thus promoting heme uptake in neurons. We also ascertained that HCP1 expression can be induced by GC through a transcription factor, Krüppel-like factor 4 (KLF4). These results may gain new insights into the etiology of heme uptake and iron accumulation in PS rats, and find new therapeutic targets of iron accumulation in Parkinson’s disease or Alzheimer’s disease.

Section: Resultssupporting

confidence: 92%

Physiological stress-induced corticosterone increases heme uptake via KLF4-HCP1 signaling pathway in hippocampus neurons

Shen

et al. 2017

Sci Rep

Self Cite

“…Is it possible that changes in stress hormones during pregnancy may also contribute to IR other than OS? Our previous study suggested that stress adaptation disturbance during pregnancy may aggravate stress-induced hyperglycemia in rats 10,11 . The aim of the present study was to document the association between stress hormones and IR in women with GDM, in an attempt to gain insights into the pathogenesis of GDM.…”

Section: Introductionmentioning

confidence: 95%

Stress adaptation is associated with insulin resistance in women with gestational diabetes mellitus

Feng

Feng²,

et al. 2020

Nutr. Diabetes

Self Cite

Aim: Oxidative stress is known to increase the risk of insulin resistance (IR). The aim of this study was to investigate the association between stress hormones and IR in women with gestational diabetes mellitus (GDM), in an attempt to gain insights into the pathogenesis of GDM. Methods: Recruited in this study were 70 GDM women and 70 healthy pregnant women as control. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), plasma epinephrine (E), noradrenaline (NE), glucagon, and cortisol levels were detected. IR was assessed by homeostasis model assessment of IR (HOMA-IR) in both groups. Correlations among stress hormones, oxidative stress, and IR were analyzed by Pearson's correlation after log transformation. Results: Compared with the Control group, MDA was increased and anti-oxidative enzymes SOD and GSH were decreased significantly in the GDM group. Glucagon, E, and NE in the GDM group were increased by 22.42%, 36.82%, and 35.09%, respectively, as compared with those in the Control group. MDA showed a significant positive correlation, and SOD showed a negative correlation with HOMA-IR in the GDM group. In addition, HOMA-IR was positively related to glucagon, E, NE, and cortisol. Conclusions: Elevation of stress hormones and stress adaptation disturbance may be associated with the pathogenesis of GDM in pregnant women.

“…Iron also affects hypoxia inducible factors, which can downregulate glucose transporters and decrease glucose tolerance [ 12 ]. In an experiment with stressed rats, a high-iron diet induced persistent hyperglycemia, and aggravated stress induced iron deposition and oxidative stress injury to the liver [ 13 ]. It has also been shown that iron metabolism is related to insulin resistance in GDM women, suggesting that change in iron metabolism may be involved in the pathogenesis of GDM by aggravating stress hyperglycemia [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Interaction of Iron Homeostasis and Fatty Acid Metabolism in the Development of Glucose Intolerance in Women with Previous Gestational Diabetes Mellitus

Källner,

Krook,

Sandberg

et al. 2023

Nutrients

A gestational diabetes mellitus (GDM) diagnosis during pregnancy means an increased risk of developing type 2 diabetes later in life. By following up with women after GDM we aimed to examine the relationship between iron parameters, individual fatty acids (FAs) and desaturases in the development of impaired glucose metabolism (IGM). Based on an oral glucose tolerance test (OGTT), six years after GDM, 157 women were grouped as having normal glucose tolerance (NGT) or IGM. Fasting serum FAs, activity of desaturases and iron parameters (ferritin, transferrin, iron, soluble transferrin receptor, total iron binding capacity, hepcidin) were measured, and clinical and anthropometric measurements taken. Soluble transferrin receptor was higher in the IGM group compared to the NGT group (3.87 vs. 3.29 mg/L, p-value = 0.023) and associated positively with saturated FAs and negatively with monounsaturated FAs in the IGM group (adjusted for BMI, age and high sensitivity C-reactive protein; p-value < 0.05). Iron, as well as transferrin saturation, showed a positive association with MUFAs and desaturase activity. These associations were not seen in the NGT group. These results suggest that iron homeostasis and FA metabolism interact in the development of glucose intolerance in women with previous GDM.