The most physiologically important sensors for systemic glucoregulation are located in extracranial sites. Recent evidence suggests that the carotid body may be one such site. We assessed rat carotid body afferent neural output in response to lowered glucose, indirectly by measurement of ventilation, and directly by recording single or few-fibre chemoafferent discharge, in vitro. Insulin (0.4 U kg −1 min −1 )-induced hypoglycaemia (blood glucose reduced by ca 50% to 3.4 ± 0.1 mmol l −1 ) significantly increased spontaneous ventilation (V E ) in sham-operated animals but not in bilateral carotid sinus nerve sectioned (CSNX) animals. In both groups, metabolic rate (measured asV O 2 ) was almost doubled during hypoglycaemia. The ventilatory equivalent (V E /V O 2 ) was unchanged in the sham group leading to a maintained control level of P a,CO 2 , buṫ V E /V O 2 was significantly reduced in the CSNX group, giving rise to an elevation of 6.0 ± 1.3 mmHg in P a,CO 2 . When pulmonary ventilation in sham animals was controlled and maintained, phrenic neural activity increased during hypoglycaemia and was associated with a significant increase in P a,CO 2 of 5.1 ± 0.5 mmHg. Baseline chemoreceptor discharge frequency, recorded in vitro, was not affected, and did not increase when the superfusate [glucose] was lowered from 10 mM to 2 mM by substitution with sucrose: 0.40 ± 0.20 Hz to 0.27 ± 0.15 Hz, respectively (P > 0.20). We suggest therefore that any potential role of the carotid bodies in glucose homeostasis in vivo is mediated through its transduction of some other metabolically derived blood-borne factor rather than glucose per se and that this may also provide the link between exercise, metabolic rate and ventilation.

This study was performed to investigate the protective and therapeutic effects of resveratrol (RES) against CdCl2-induced toxicity in rat testes. Seven experimental groups of adult male rats were formulated as follows: A) controls+NS, B) control+vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl2+NS, E) CdCl2+vehicle, F) RES followed by CdCl2 and M) CdCl2 followed by RES. At the end of the protocol, serum levels of FSH, LH and testosterone were measured in all groups, and testicular levels of TBARS and superoxide dismutase (SOD) activity were measured. Epididymal semen analysis was performed, and testicular expression of Bcl-2, p53 and Bax was assessed by RT-PCR. Also, histopathological changes of the testes were examined microscopically. Administration of RES before or after cadmium chloride in rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. RES not only attenuated cadmium chloride-induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of pro-apoptotic genes p53 and Bax. Resveratrol protected against and partially reversed cadmium chloride testicular toxicity via upregulation of Bcl2 and downregulation of p53 and Bax gene expression. The antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression.

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We have utilized an anaesthetized rat model of insulin-induced hypoglycaemia to test the hypothesis that peripheral chemoreceptor gain is augmented during hypermetabolism. Insulin infusion at 0.4 U kg (-1)min(-1) decreased blood glucose concentration significantly to 3.37 +/- 0.12 mmol l(-1). Whole-body metabolism and basal ventilation were elevated without increase in P(a,CO(2)) (altered non-significantly from the control level, to 37.3 +/- 2.6 mmHg). Chemoreceptor gain, measured either as spontaneous ventilatory airflow sensitivity to P(a,CO(2)) during rebreathing, or by phrenic minute activity responses to altered P(a,CO(2)) induced by varying the level of artificial ventilation, was doubled during the period of hypermetabolism. This stimulatory effect was primarily upon the mean inspiratory flow rate, or phrenic ramp component of breathing and was reduced by 75% following bilateral carotid sinus nerve section. In vitro recordings of single carotid body chemoafferents showed that reducing superfusate glucose concentration from 10 mM to 2 mM reduced CO(2) chemosensitivity significantly from 0.007 +/- 0.002 Hz mmHg(-1) to 0.001 +/- 0.002 Hz mmHg(-1). Taken together, these data suggest that the hyperpnoea observed during hypermetabolism might be mediated by an increase in the CO(2) sensitivity of the carotid body, and this effect is not due to the insulin-induced fall in blood glucose concentration.

Aim: To investigate the possible role of oxidative stress as a common mediator of apoptosis and cardiac damage in diabetes. Materials and Methods:This experimental work was conducted on 5 groups of Wistar rats. Group I was the control group. Diabetes type 1 was induced in other groups (by streptozotocin) and animals received insulin or vitamin E (300 mg /kg body weight), both insulin and vitamin E, or no treatment for 4 weeks according to their group. At the end of the study, serum and cardiac tissues were examined for biochemical parameters of cardiac function, oxidative stress and apoptosis. Electron microscopy pictures of cardiac tissue were also evaluated for signs of cardiac damage.Results: Markers of oxidative stress, apoptosis, inflammation as well as manifestations of cardiac damage as assessed by electron microscopy were significantly decreased in rats treated with both insulin and vitamin E when compared with untreated diabetic rats or rats treated with either insulin or vitamin E alone.Conclusion: Administration of both vitamin E and insulin was effective in reducing markers of oxidative stress and apoptosis and improving parameters of cardiac function in experiments animals. Antioxidants might prove beneficial as an adjuvant treatment in addition to insulin in type 1 diabetes associated with manifestations of cardiac complications.