Oxidative stress suppresses PHB2-mediated mitophagy in ß-cells via the Nrf2/PHB2 pathway.

AIMS/INTRODUCTION: Mitochondrial damage caused by oxidative stress is a main driver of pancreatic ß-cell dysfunction in the pathogenesis of type 2 diabetes mellitus. Prohibitin2 (PHB2) is a vital inner mitochondrial membrane protein that participates in mitophagy to remove the damaged mitochondria. This study aimed to investigate the role and mechanisms of PHB2-mediated mitophagy in oxidative stress-induced pancreatic ß-cell dysfunction. MATERIALS AND METHODS: PHB2 and mitophagy-related protein expression were analyzed by real-time polymerase chain reaction and western blotting in RINm5F cells treated with H2O2 and islets of diabetic rats. Mitophagy was observed by mitochondrial and lysosome colocalization. RINm5F cells were transfected by phb2 siRNA or overexpression plasmid to explore the role of PHB2 in mitophagy of RINm5F cells. The mechanism of Nrf2 regulating PHB2 was explored by Nrf2 inhibitor and agonist. RESULTS: The expression of PHB2, mitophagy related protein PINK1, and Parkin were decreased in RINm5F cells incubated with H2O2 and in islets of diabetic rats. Overexpression of PHB2 protected ß-cells from oxidative stress by promoting mitophagy and inhibiting cell apoptosis, whereas transfection with PHB2 siRNA suppressed mitophagy. Furthermore, PHB2-mediated mitophagy induced by oxidative stress was through the Nrf2/PHB2 pathway in ß-cells. Antioxidant NAC alleviated oxidative stress injury by promoting PHB2-mediated mitophagy. CONCLUSION: Our study suggested that PHB2-mediated mitophagy can protect ß-cells from apoptosis via the Nrf2/PHB2 pathway under oxidative stress. Antioxidants may protect ß-cell from oxidative stress by prompting PHB2-mediated mitophagy. PHB2-mediated mitophagy as a potential mechanism takes part in the oxidative stress induced ß-cell injury.

Application opportunity of Doppler ultrasound combined with CT angiography in diabetic lower extremity arterial disease and the analysis of the risk factors.

Objective: This study examined the potential of combining Doppler ultrasound (DUS) and CT angiography (CTA) for early detection and intervention of lower extremity arterial disease (LEAD) in diabetes.Concurrently, risk factors influencing LEAD progression were analyzed. Methods: 106 Type-2 diabetes patients with LEAD, having undergone DUS and CTA, were divided into four stages according to Fontaine stage. Results of DUS and CTA were compared across stages and potential risk factors were analyzed. Results: Positive detection rates of LEAD differed between DUS and CTA for Fontaine stages I and II (P < 0.05), with no significant difference for stages III and IV (P > 0.05). CTA identified subgroups with mild to moderate stenosis and severe stenosis or occlusion, with positive rates on DUS of 17.95% and 89.9% respectively. Hypertension was found as an independent risk factor affecting LEAD progression. Conclusion: CTA should be performed early for LEAD in diabetes patients at Fontaine stages I and II, regardless of DUS results. For diabetes patients with LEAD, stringent blood pressure control is crucial to delay disease progression.

Efficacy, safety and influencing factors of intra-calf muscular injection of bone marrow mononuclear cells in the treatment of type 2 diabetes mellitus-induced lower extremity vascular disease.

The efficacy, safety and impact of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) associated with the intra-calf muscular injection of bone marrow mononuclear cells (BMMCs) in the treatment of type 2 diabetes mellitus (T2DM)-induced lower extremity vascular disease (LEVD) were evaluated. Patients with T2DM-LEVD were randomly divided into a control group and BMMCs group to assess the efficacy and safety of the treatment; serum VEGF and bFGF levels were detected. The BMMCs group was divided into superior genicular artery (SGA) and inferior genicular artery (IGA) subgroups as well as low-dose and high-dose subgroups for the comparison of efficacy indices. The BMMCs group exhibited significantly improved indices (P<0.05) compared with the control group and no fatalities or cancer occurred. There were no significant changes in serum VEGF and bFGF levels (P>0.05). The claudication distance in the IGA subgroup was significantly greater that in the SGA subgroup (P<0.05); the low-dose subgroup and the high-dose subgroup did not demonstrate any significant differences in each index (P>0.05). BMMC treatment for T2DM-LEVD was found to be safe and effective and had no significant impact on serum VEGF and bFGF levels in the short term; However, the degree of LEVD may affect its efficacy.

Correlation Between IGFs-Related Proteins Expression and Incidence of Colorectal Cancer in Diabetic Patients and Related Mechanisms.

BACKGROUND: Diabetes mellitus a common metabolic disorder with hyperglycemia, is caused by the interaction of genetic and environmental factors. Approximately 12~20% of diabetic patients have risk of colorectal cancer. Recent studies revealed that the insulin-like growth factor system (IGFs) plays an important role in tumor occurrence. This study thus investigated the relationship between IGFs-related proteins in diabetic patients and the incidence of colorectal carcinoma. MATERIAL/METHODS: A retrospective study was performed in a total of 206 individuals, including 85 diagnosed with diabetes. The incidence of colorectal cancer was tracked, along with the detection of IGFs expression in serum. During the surgical resection, tumor tissues and adjacent tissues were collected and quantified for IGFs expression level. RESULTS: We found no significant difference in age or sex between the diabetic and control groups. Diabetic patients, however, had elevated body weight and higher incidence of colorectal cancer compared to non-diabetic controls (p<0.05). The diabetic group also had higher IGF-I and IGF-IR mRNA levels in serum, while IGFBP-6 expression was down-regulated. In comparison to adjacent healthy tissues, tumor tissue had higher levels of IGF-I and IGF-IR but lower levels of IGFBP-6 (p<0.05). CONCLUSIONS: Our study showed higher incidence of colorectal cancer in diabetics compared to non-diabetics. The occurrence of colorectal cancer in diabetic patients may be associated with elevated IGFs-related protein expression level.