Acute psychological stress results in the rapid development of insulin resistance

Abstract

In recent years, the roles of chronic stress and depression as an independent risk factor for decreased insulin sensitivity and the development of diabetes have been increasingly recognized. However, an understanding and the mechanisms linking insulin resistance and acute psychological stress are very limited. We hypothesized that acute psychological stress may cause the development of insulin resistance, which may be a risk factor in developing type 2 diabetes. We tested the hypothesis in a well-established mouse model using 180 episodes of inescapable foot shock (IES), followed by a behavioral escape test. In this study, mice that received IES treatment were tested for acute insulin resistance by measuring glucose metabolism and insulin signaling. When compared to normal and sham mice, mice that were exposed to IES resulting in escape failure (defined as IES with behavioral escape failure) displayed elevated blood glucose levels in both glucose tolerance and insulin tolerance tests. Furthermore, mice with IES exposure and behavioral escape failure exhibited impaired hepatic insulin signaling via the insulin-induced insulin receptor/insulin receptor substrate 1/Akt pathway, without affecting similar pathways in skeletal muscle, adipose tissue and brain. Additionally, a rise in murine growth-related oncogene KC/GRO was associated with impaired glucose metabolism in IES mice, suggesting a mechanism by which psychological stress by IES may influence glucose metabolism. The present results indicate that psychological stress induced by IES can acutely alter hepatic responsiveness to insulin and affect whole-body glucose metabolism.

Stress Aggravates High-Fat-Diet-Induced Insulin Resistance via a Mechanism That Involves the Amygdala and Is Associated with Changes in Neuroplasticity

“…This acute stress impaired the insulin signaling pathway in the liver, but not in the adipose, muscle, or brain (i.e., hypothalamus, hippocampus, and amygdala) tissues [35]. The authors concluded that psychological stress acutely altered hepatic insulin sensitivity and affected the systemic glucose metabolism in normal mice [35]. In agreement with their findings, we found that chronic SD stress could aggravate HFD-induced insulin resistance.…”

“…Mice exposed to a 180-episode inescapable foot shock increased blood glucose levels during the glucose tolerance and insulin tolerance tests. This acute stress impaired the insulin signaling pathway in the liver, but not in the adipose, muscle, or brain (i.e., hypothalamus, hippocampus, and amygdala) tissues [35]. The authors concluded that psychological stress acutely altered hepatic insulin sensitivity and affected the systemic glucose metabolism in normal mice [35].…”

“…However, the mechanisms underlying the interaction between psychological stress and insulin resistance are still unclear, although a few pioneering studies have shed light on this puzzle. Li et al [35] reported that acute stress could lead to rapid development of insulin resistance. Mice exposed to a 180-episode inescapable foot shock increased blood glucose levels during the glucose tolerance and insulin tolerance tests.…”

Elevated Brain Glucose and Glycogen Concentrations in an Animal Model of Depression

“…Excesses of these hormones can evoke insulin resistance, i.e. reduce the sensitivity of the tissue to the action of these hormones [17]. As glucose is the brain's main energy source for the proper synthesis and function of neurotransmitters and the formation of appropriate amounts of NADPH to remove excessive levels of reactive oxygen species, changes in brain glucose levels and/or glucose metabolism may link stress or excessive glucocorticoid levels to the alterations responsible for the development of depression [18].…”

The effects of short term stress on the central and peripheral nitrergic system

“…Following the release of the stress hormone corticosterone, blood glucose concentrations rapidly elevate through processes of hepatic gluconeogenesis and insulin resistance necessary for the adaptive responses to stress, including increased mitochondrial ATP production via oxidative phosphorylation (Teague et al, 2007;Du et al, 2009;Li et al, 2013). This glucocorticoid-driven increase in cellular metabolism is subject to a small percentage of electron 'leakage' from the electron transport chain, ultimately generating free radicals such as superoxide in place of water molecules, in addition to other members of the reduction/oxidation (redox) system such as nitric oxide (NO) (Spiers et al, 2014a).…”