Problems associated with glucose toxicity:Role of hyperglycemia-induced oxidative stress

Glucose homeostasis deficiency leads to a chronic increase in blood glucose concentration. In contrast to physiological glucose concentration, chronic super-physiological glucose concentration negatively affects a large number of organs and tissues. Glucose toxicity means a decrease in insulin secretion and an increase in insulin resistance due to chronic hyperglycemia. It is now generally accepted that glucose toxicity is involved in the worsening of diabetes by affecting the secretion of B-cells. Several mechanisms have been proposed to explain the adverse effects of hyperglycemia. It was found that persistent hyperglycemia caused the functional decline of neutrophils. Infection is thus the main problem resulting from glucose toxicity in the acute phase. In other words, continued hyperglycemia is a life-threatening risk factor, not only in the chronic but also the acute phase, and it becomes a risk factor for infection, particularly in the perioperative period.

Interactions between myoblasts and macrophages under high glucose milieus result in inflammatory response and impaired insulin sensitivity

BACKGROUND Skeletal muscle handles about 80% of insulin-stimulated glucose uptake and become the major organ occurring insulin resistance(IR).Many studies have confirmed the interactions between macrophages and skeletal muscle regulated the inflammation and regeneration of skeletal muscle.However,despite of the decades of research,whether macrophages infiltration and polarization in skeletal muscle under high glucose(HG)milieus results in the development of IR is yet to be elucidated.C2C12 myoblasts are well-established and excellent model to study myogenic regulation and its responses to stimulation.Further exploration of macrophages'role in myoblasts IR and the dynamics of their infiltration and polarization is warranted.AIM To evaluate interactions between myoblasts and macrophages under HG,and its effects on inflammation and IR in skeletal muscle.METHODS We detected the polarization status of macrophages infiltrated to skeletal muscles of IR mice by hematoxylin and eosin and immunohistochemical staining.Then,we developed an in vitro co-culture system to study the interactions between myoblasts and macrophages under HG milieus.The effects of myoblasts on macrophages were explored through morphological observation,CCK-8 assay,Flow Cytometry,and enzyme-linked immunosorbent assay.The mediation of macrophages to myogenesis and insulin sensitivity were detected by morphological observation,CCK-8 assay,Immunofluorescence,and 2-NBDG assay.RESULTS The F4/80 and co-localization of F4/80 and CD86 increased,and the myofiber size decreased in IR group(P<0.01,g=6.26).Compared to Mc group,F4/80+CD86+CD206-cells,tumor necrosis factor-α(TNFα),inerleukin-1β(IL-1β)and IL-6 decreased,and IL-10 increased in McM group(P<0.01,g>0.8).In McM+HG group,F4/80+CD86+CD206-cells,monocyte chemoattractant protein 1,TNFα,IL-1βand IL-6 were increased,and F4/80+CD206+CD86-cells and IL-10 were decreased compared with Mc+HG group and McM group(P<0.01,g>0.8).Compered to M group,myotube area,myotube number and E-MHC were increased in MMc group(P<0.01,g>0.8).In MMc+HG group,myotube area,myotube number,E-MHC,GLUT4 and glucose uptake were decreased compared with M+HG group and MMc group(P<0.01,g>0.8).CONCLUSION Interactions between myoblasts and macrophages under HG milieus results in inflammation and IR,which support that the macrophage may serve as a promising therapeutic target for skeletal muscle atrophy and IR.

Relationship between perioperative glycemic control and postoperative infections

Perioperative hyperglycemia in critically ill surgery patients increases the risk of postoperative infection (POI), which is a common, and often costly, surgical complication. Hyperglycemia is associated with abnormalities in leukocyte function, including granulocyte adherence, impaired phagocytosis, delayed chemotaxis, and depressed bactericidal capacity. These leukocyte deficiencies are the cause ofinfection and improve with tight glycemic control, which leads to fewer POIs in critically ill surgical patients. Tight glycemic control, such as intensive insulin therapy, has a risk of hypoglycemia. In addition, the optimal targeted blood glucose range to reduce POI remains unknown. Since 2006, we have investigated tight perioperative blood glucose control using a closed-loop artificial endocrine pancreas system, to reduce POI and to avoid hypoglycemia. In this Topic Highlight, we review the relationship between perioperative glycemic control and POI, including the use of the artificial pancreas.

β-Islet cell regeneration potential of Mirabilis jalapa in hyperglycemic rats

Objective:To investigate the role of Mirabilis jalapa root extracts in restoration of glucose homeostasis in alloxan-induced hyperglycemic Wistar albino rats.Methods:Experimental hyperglycemic rats were treated daily with 200 and 400 mg/kg of Mirabilis jalapa extracts after initial fasting for 6 h.Two-hour postprandial glucose and changes in body weight were monitored during treatment.After 14 d,the rats were sacrificed and blood was collected for biochemical assessment of serum glucose and insulin levels,lipid profile,and oxidative stress markers.Histopathological examinations of harvested pancreas were also carried out.Results:Mirabilis jalapa root extracts at 200 and 400 mg/kg increased the body weight of hyperglycemic rats.Postprandial glucose levels of the extract-treated hyperglycemic groups progressively declined during treatment compared with the untreated hyperglycemic control group(P<0.05).The lipid profile indices of the untreated negative control group were significantly elevated(P<0.05),which were reversed by treatment with Mirabilis jalapa extracts.The remarkable increases in antioxidant enzyme activities and a significant decrease in malondialdehyde levels were observed in the hyperglycemic group treated with Mirabilis jalapa extracts.Mirabilis jalapa extracts also significantly increased serum insulin levels(P<0.05).In addition,histopathological examinations of the pancreas revealed a significant cell population within the islet nests of the extract-treated hyperglycemic groups.Conclusions:Mirabilis jalapa extract can restore glucose homeostasis and show hypoglycemic and hypolipidemic effects in hyperglycemic rats.Further studies are needed to verify the active components of the plant and the underlying mechanism of action in the future.

Paradox of Using Intensive Lowering of Blood Glucose in Diabetics and Strategies to Overcome It and Decrease Cardiovascular Risks

Hyperglycemia significantly increases the risk of cardiovascular disease （CVD） in diabetics. However, it has been shown by a series of large scale international studies that intensive lowering of blood glucose levels not only has very limited benefits against cardiovascular problems in patients, but may even be harmful to patients at a high risk for CVD and/or poor long-term control of blood glucose levels. Therefore, Western medicine is faced with a paradox. One way to solve this may be administration of Chinese herbal medicines that not only regulate blood glucose, blood fat levels and blood pressure, but also act on multiple targets. These medicines can eliminate cytotoxicity of high glucose through anti-inflammatory and anti-oxidant methods, regulation of cytokines and multiple signaling molecules, and maintenance of cell vitality and the cell cycle, etc. This allows hyperglycemic conditions to exist in a healthy manner, which is called ＂harmless hyperglycemia＂ Furthermore, these cardiovascular benefits go beyond lowering blood glucose leve^s. The mechanisms of action not only avoid cardiovascular injury caused by intensive lowering of blood glucose levels, but also decrease the cardiovascular dangers posed by hyperglycemia.