Inhibition of extracellular signal-regulated kinase downregulates endoplasmic reticulum stress-induced apoptosis and decreases brain injury in a cardiac arrest rat model.

Cerebral ischemia-reperfusion injury (CIRI) is the predominant cause of neurological disability after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The endoplasmic reticulum stress (ERs)-induced apoptosis plays an important role in neuronal survival/death in CIRI. Our previous studies reported that the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, alleviates CIRI after CA/CPR. Whether ERs-induced apoptosis is involved in the neuroprotection of PD98059 remains unknown. This study aims to investigate the effects of ERK inhibition by PD98059 on ERs-induced apoptosis after CIRI in the CA/CPR rat model. The baseline characteristics of male adult Sprague-Dawley (SD) rats in all groups were evaluated before CA/CPR. The SD rats that survived from CA/CPR were randomly divided into 3 groups (n=12/group): normal saline group (1 ml/kg), dimethylsulfoxide (DMSO, the solvent of PD98059, 1 ml/kg) group, PD98059 group (0.3 mg/kg). Another 12 SD rats were randomly selected as the Sham group. Twenty-four hours after resuscitation, neural injury was assessed by survival rate, neurological deficit scores (NDS) and Nissl staining; apoptosis of brain cells was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining; mRNA expression and protein levels of ERs-related protein BIP, PERK, ATF4 and CHOP were checked with RT-PCR and Western Blot. The results showed that there were no significant differences in baseline characteristics before CA/CPR among all groups. PD98059 significantly improved survival rate and NDS, increased the Nissl bodies in neurons, reduced apoptosis, downregulated the mRNA transcription and expression levels of BIP, PERK, ATF4 and CHOP at 24 h after CA/CPR. Our results demonstrate that inhibition of ERK by PD98059 alleviates ERs-induced apoptosis via BIP-PERK-ATF4-CHOP signaling pathway and mitigates CIRI in the CA/CPR rat model.

[A clinical analysis of insulin antibody in type 2 diabetic patients].

This study was conducted to evaluate the relationship between serum insulin levels and the production of insulin antibody (IA) in type 2 diabetes (T2DM). A total of 647 T2DM were included. Among them, 20.9% patients were IA positive, who were elder and had a longer duration, lower BMI, a higher positive rate of glutamic acid decarboxylase antibody(GADAb) and higher serum insulin levels during an insulin secretion test. More patients were treated with insulin in IA positive group than in IA negative group (65.9% vs 41.0%, P=0.000). Fasting serum insulin level was associated with occurrence of IA in all patients (OR=1.02, P=0.001) and insulin treated patients (OR=1.033, P=0.002). The cut-off point of fasting serum insulin level for predicting IA positive was 17.87 mIU/L (sensitivity 55.1%, specificity 89.0%). Exogenous insulin use is associated with the presence of IA. Fasting serum insulin level can be used as a predictor for the production of IA in insulin-treated patients.

Delayed gastric emptying is related to cardiovascular autonomic neuropathy in Chinese patients with type 2 diabetes.

BACKGROUND AND STUDY AIMS: Delayed gastric emptying (DGE) is the commonest gastrointestinal (GI) complication in type 2 diabetes. We aimed to evaluate the association between DGE and cardiovascular autonomic neuropathy (CAN) in type 2 diabetes. PATIENTS AND METHODS: A total of 71 Chinese patients (39 men and 32 women, aged 60-90 years) and 30 controls (12 men and 18 women, aged 50-79 years) were studied in Nanjing, China. The gastric emptying was assessed by 13C-octanoic acid breath test (OBT) and gastric emptying ultrasonography (GEU). Cardiovascular autonomic neuropathy (CAN) was assessed by a scoring system being validated before. RESULTS: The diabetic patients, except for a higher plasma glucose level, had similar characteristics compared to the non-diabetic controls. Diabetic patients had higher incidence of DGE and CAN than controls (48.5% vs. 10.7%, p = 0.001). Among diabetic patients with DGE (n = 27), 18 (66.7%) had CAN and 9 (33.3%) did not. Corresponding figures for those without DGE (n = 39) were 14 (35.9%) and 25 (64.1%), respectively (p = 0.014). Diabetes was independently associated with the risk of DGE with odd ratio (95% CI) of 15.6 (1.92, 127.06) (p = 0.010). The presence of diabetes or CAN was independently associated with the half gastric emptying time after adjusting for age, gender, plasma glucose and blood pressure. CONCLUSIONS: We found a much prolonged gastric emptying time in Chinese patients with type 2 diabetes as compared to non-diabetic controls. There was a high rate of CAN in diabetic patients, and it was associated with gastric emptying.