Chronic stress and carbohydrate metabolism: Persistent changes and slow return to normalcy in male albino rats

Abstract

The present study tested the hypothesis that long-term repeated exposure to stressors results in irreversible changes in carbohydrate metabolism. Groups of adult male rats (five per group) were restrained for 1 h and 4 h later were forced to swim for 15 min everyday for 2, 4, or 24 weeks; five rats were autopsied after each interval. Groups of five rats exposed to stress for 2 or 4 weeks were maintained without further treatment (recovery groups) for up to 24 weeks. The fasting blood glucose concentration, measured at weekly intervals, was significantly higher in the stressed rats than in controls throughout the experiment, except in the 24th week, whereas that of the recovery groups was significantly higher than controls only up to the 8th week after the end of stress exposure and then reached normalcy. The blood concentrations of glucose, lactate, and pyruvate were significantly higher in the 2 and 4 weeks stress groups than in controls, whereas, except for lactate, in rats stressed for 24 weeks these values did not significantly differ from those in controls. These changes were accompanied by increased gluconeogenesis and glycogenolysis as shown by alterations in activities of hepatic carbohydrate metabolizing enzymes and unaltered blood insulin concentrations in rats stressed for 2, 4, and 24 weeks. Furthermore, the blood insulin levels did not significantly vary among controls and the 2, 4, and 24 weeks stress groups. The results reveal that though hyperglycemia induced by long-term stress exposure is reversible, it persists for a prolonged period, even after the termination of stress exposure, before reaching normalcy. Prevalence of hyperglycemia for a prolonged period through increased activities of hepatic enzymes in stressed rats exemplifies allostasis.

Stress and Glucose metabolism: A Review

“…It regulates the metabolism by altering the biochemical pathways to achieve stability. Indeed the state of allostasis has been demonstrated by us in rats that were exposed to chronic stress [24]. In this study consistent hyperglycemia was observed in rats for 24 weeks, following exposure to restraint for 1 h followed by forced swimming for 15 minutes after a gap of 4 hours every day for 2, 4 or 24 weeks.…”

“…altered physiological processes that may cause damage to the system [43]. For instance in our study [24] prolonged hyperglycemic condition due to stress was accompanied by insulin resistance and failure to tolerate glucose as shown by OGTT in rats. Thus when stress is persistent and it is prolonged for a long duration, the adaptive processes in the body become maladaptive resulting in pathophysiology.…”

“…A number of studies have shown the decreased liver glycogen content in response to chronic stress. For instance, our study [24] wherein rats were exposed for restraint and forced swimming every day for 2, 4 or 24 weeks, a reduction in hepatic glycogen content was observed. In addition, Kuznetsov and his coworkers [33] subjected rats to hypokinetic stress for 5, 15, 30, 45 and 60 days which resulted in decreased liver glycogen content.…”

“…Under stressful conditions, the pyruvate produced by glycolysis may be channeled towards the production of glucose or it might end up in producing high lactate because of the reduced activity of pyruvate dehydrogenase (PDH). Reduced pyruvate dehydrogenase activity has been observed under chronic stress condition [23,24]. Stress is known to alter PDH activity [25] by increasing the concentration of pyruvate dehydrogenase kinase which inactivates PDH by phosphorylating it [26].…”

Efficacy of an Active Compound of the Herb, Ashwagandha in Prevention of Stress Induced Hyperglycemia

“…phosphoenolpyruvate carboxykinase (PEPCK), fructose-1, 6-bisphosphatase and glucose-6-phosphatase (G6Pase) and serves as a mechanism by which the availability of glucose is maintained. An increase in activities of hepatic G6Pase and PEPCK under different stressful conditions has been reported [9][10][11][12]. Hyperglycemia due to increased gluconeogenesis has a negative impact on the body as it results in insulin resistance [13].…”