Early postnatal stress impairs insulin secretion in response to psychological stress in adult rats.

PURPOSE: Adversity in early life can induce metabolic defects in exposure to stress in adulthood. Therefore, the exploration of involving mechanisms can be helpful in the treatment of metabolic disorders. So, the present study was conducted in terms of exploring the effects of interaction between early postnatal stress and young adulthood psychological stress on insulin secretion and pancreatic GLUT-2 levels in male rats. METHODS: Footshock as a model of early life stress (at 2 weeks of age) and psychological stress induced by communication box as a model of young adulthood stress (at 8-10 weeks of age) were induced in male Wistar rats for five consecutive days (2 times/day). Blood samples were drawn to measure glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ß-cell dysfunction (HOMA-B), before and after stress protocol in young adult rats. Corticosterone was measured on days 1 and 5 of stress induction. The day after the stress period, factors including glucose tolerance, TNF-alpha, isolated islets' insulin output and levels of pancreatic GLUT-2 protein via western blotting were determined. RESULTS: The combination of early footshock exposure and psychological stress during adulthood did not affect plasma corticosterone, but increased plasma insulin, HOMA-IR, HOMA-B and TNF-alpha levels. Plasma TNF was not only increased by the combination of both stressors, but also after only E STR exposure. HOMA-IR was increased in both Psy STR and E + Psy-STR groups. Plasma glucose just increased in Psy STR group. The combination of these two life stressors further increased the in vitro insulin secretion from isolated islets in response to 16.7-mM glucose. The level of Glut2 was increased in Psy STR and decreased in both E STR and E + Psy STR groups. Finally, glucose tolerance was impaired and glucose-stimulated insulin secretion was increased in E + Psy STR group. CONCLUSIONS: In conclusion, inducing stress in early life makes the organism more susceptible to metabolic defects in exposure to psychological stress later in life.

High-fat diet with stress impaired islets' insulin secretion by reducing plasma estradiol and pancreatic GLUT2 protein levels in rats' proestrus phase.

This study was conducted to determine whether two estrus phases (proestrus and diestrus) in female rats may influence the metabolic response to a high-fat diet and/or stress, focusing on pancreatic insulin secretion and content. Animals were divided into high-fat and normal diet groups, then each group was subdivided into stress and non-stress groups, and finally, each one of these was divided into proestrus and diestrus subgroups. At the end of high-fat diet treatment, foot-shock stress was applied to the animals. Then, blood samples were taken to measure plasma factors. Finally, the pancreas was removed for determination of glucose transporter 2 (GLUT2) protein levels and assessment of insulin content and secretion of the isolated islets. In the normal and high-fat diet groups, stress increased plasma corticosterone concentration in both phases. In both study phases, high-fat diet consumption decreased estradiol and increased leptin plasma levels. In the high-fat diet group in response to high glucose concentration, a reduction in insulin secretion was observed in the proestrus phase compared with the same phase in the normal diet group in the presence and absence of stress. Also, high-fat diet decreased the insulin content of islets in the proestrus phase compared with the normal diet. High-fat diet and/or stress caused a reduction in islet GLUT2 protein levels in both phases. In conclusion, it seems possible that high-fat diet alone or combined with foot-shock, predispose female rats to impaired insulin secretion, at least in part, by interfering with estradiol levels in the proestrus phase and decreasing pancreatic GLUT2 protein levels.

Glucose-stimulated insulin secretion: Effects of high-fat diet and acute stress.

BACKGROUND: One of the major topics in modern societies is the study of relationships between diet, stress and incidence of metabolic disorders. AIM: This study aimed to investigate possible impairment in glucose-stimulated insulin secretion induced by a high-fat (cow intra-abdominal fat) diet in response to acute stress. MATERIALS AND METHODS: Male Wistar rats were divided into high-fat and normal diet groups and each group was further divided into stress and control subgroups. Stress was induced by a communication box. Plasma levels of glucose, insulin and corticosterone were measured in both diet groups. Glucose tolerance, homeostasis model assessment of insulin resistance (HOMA-IR) index, glucose-stimulated insulin secretion from isolated islets, food and energy intake as well as body weight were also evaluated. RESULTS: In the normal diet group, physical stress increased plasma glucose concentrations. In both diet groups, plasma corticosterone levels increased after stress. HOMA-IR index decreased in high-fat fed rats. Food intake decreased while energy intake increased in the high-fat diet rats. Body weight in both diet groups increased in a similar manner. The high-fat diet did not affect insulin secretion; however, stress decreased insulin secretion from isolated islets of both diet groups. Only in the high fat diet group did physical stress increase insulin secretion at 16.7 mM glucose. CONCLUSIONS: The cow intra-abdominal fat, did not affect either plasma glucose and insulin concentrations or glucose-induced insulin secretion. Interestingly, it seems that the high-fat diet enabled the islets of the physically stressed rats to secrete more insulin in response to high glucose concentrations.

Saffron (Crocus sativus) ethanolic extract and its constituent, safranal, inhibits morphine-induced place preference in mice.

The effects of saffron ethanolic extract and its constituent, safranal, on the acquisition and expression of morphine-induced place preference (CPP) in male Swiss Webster mice (20-25 g) were investigated in the present study. An unbiased place conditioning method was applied for assessment of morphine reward properties. The saffron extract and safranal were administered intraperitoneally (i.p.) during (acquisition) or after induction (expression) of morphine CPP. In a pilot study, the extract and safranal were alone administered to the animals to assess if they have any reward properties. Subcutaneous (s.c.) of morphine (4 and 8 mg kg(-1)) and extract (50 mg kg(-1); i.p.) induced CPP. Extract (10, 50 and 100 mg kg(-1); i.p.) reduced the acquisition and expression of morphine CPP. The same results were obtained when safranal (1, 5 and 10 mg kg(-1), i.p.) was used. It may be concluded that both ethanolic saffron extract and safranal can inhibit the acquisition and expression of morphine-induced CPP in the mice.

Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.

Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14th and 21st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.

Plasma corticosterone, insulin and glucose changes induced by brief exposure to isoflurane, diethyl ether and CO2 in male rats.

The impact of anesthetic agents on endocrine and metabolic factors is an important issue. The present study has compared the effects of a short-term exposure to diethyl ether, isoflurane, or CO2 on plasma corticosterone, insulin and glucose concentrations since the duration of anesthetic exposure may have an effect on those factors. Male rats were divided into fed and fasted groups. The experimental rats were briefly exposed to diethyl ether, isoflurane, or CO2 (the degree of anesthesia was identical), while a control group was not exposed to the anesthetics. In the fed rats, diethyl ether exposure increased the levels of plasma glucose. CO2 exposure decreased plasma corticosterone and increased plasma glucose levels. Isoflurane exposure caused no changes in plasma corticosterone, glucose, or insulin levels. In the fasted rats, diethyl ether exposure increased plasma corticosterone and reduced plasma insulin levels. The plasma corticosterone and insulin levels were significantly increased by CO2) exposure. Isoflurane exposure decreased plasma insulin levels. A brief exposure to either diethyl ether or CO2 changed the plasma corticosterone, glucose, and insulin levels in fed and/or fasted rats. However, isoflurane exposure had the least effect on the concentration of these factors in both the fed and fasted states.

Effect of chronic psychological stress on insulin release from rat isolated pancreatic islets.

Despite documented studies, the exact role of stress on diabetes is still unclear. The present study investigates the effect of chronic psychological stress on insulin release from isolated rat pancreatic islets. Male Wistar rats were divided into two groups of control and stressed (n=8/group). The animals of the stressed group were exposed to restraint stressors (1 h twice daily) for 15 or 30 consecutive days. At the beginning and end of the experimental periods, the animals were weighed and blood samples taken to determine the fasting plasma levels of glucose, insulin and corticosterone. On the following day the pancreatic islets of 5/group of the above animals were isolated and the static release of insulin in the presence of different glucose concentrations (2.8, 5.6, 8.3, 16.7 mM) was assessed. The results showed that in the stressed group, fasting plasma glucose levels were increased significantly on the 15th day as compared to the control group. However there was no significant increase on the 30th day. Fasting plasma insulin was significantly decreased on the 15th and 30th days of the experiment in the stressed group. Stressed rats showed significantly higher fasting plasma corticosterone levels, only on the 15th day, as compared to the control rats. In response to increasing concentrations of glucose, insulin release from islets of the stressed group was increased significantly on the 30th day of the experiment as compared to the control group. We conclude that chronic psychological stress could increase responsiveness of pancreatic beta cells to glucose, in vitro, and thus, low insulin levels of the stressed animals, in vivo, may be due to reason(s) other than the reduction of insulin releasing capacity of pancreatic beta cells.