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Liraglutide, a glucagon-like peptide-1 receptor agonist, is an anti-diabetic medicine associated with a reduced risk of fracture in diabetic patients. In the present study, rats with streptozotocin (STZ)-induced diabetes and/or bilateral ovariectomy (OVX) were treated with liraglutide for eight weeks. Liraglutide treatment increased insulin secretion and managed blood glucose levels in the rats following STZ-induced diabetes. In addition, STZ- and OVX-induced reduction of femoral bone mineral density and destruction of bone microarchitecture were alleviated by liraglutide. STZ decreased, whereas OVX increased, serum osteocalcin (OC) level (a bone formation marker) and osteoblast counts in the trabecular bone. OVX, however not STZ, markedly increased the level of serum c-terminal telopeptide of type 1 collagen (CTX-1, a bone resorption marker) and osteoclast counts in the trabecular area. Liraglutide treatment significantly increased serum OC levels in all three osteoporotic models, however had minimal effects on osteoblast counts. Furthermore, liraglutide significantly decreased serum CTX-1 level and osteoclast numbers in OVX and STZ+OVX rats. Furthermore, the present study examined the mRNA expression and serum concentrations of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL), and liraglutide significantly decreased the RANKL/OPG ratio compared with the untreated rats, indicating that osteoclastogenesis was inhibited by liraglutide. In summary, the results suggested that liraglutide ameliorates STZ+OVX-induced bone deterioration in the rat model, primarily through the inhibition of osteoclastogenesis. These preliminary findings propose a potentially beneficial effect of liraglutide on the bone health of postmenopausal diabetic patients. [ABSTRACT FROM AUTHOR]

Curcumin is a polyphenolic compound that is extracted from Curcuma longa. It has broad anti-inflammation and anti-tumor activities. Curcumin was previously reported to exert beneficial effects on diabetes. However, the effect of curcumin on diabetes-induced lung injury is not yet clear. In this study, the effects of curcumin on lung injury induced by diabetes was explored using quantitative real time polymerase chain reaction ( PCR), enzyme-linked immunosorbent assay ( ELISA), immunohistochemistry and electrophoretic mobility shift assay. The results of this study showed that curcumin reduced oxidative stress level, inhibited the synthesis of nitric oxide and prostaglandin E2, and reduced inflammatory responses in the lungs of diabetic rats, thereby alleviating diabetes-induced lung injury. Further study of the mechanism revealed that curcumin inhibited the activation of nuclear factor ( NF)- κB which is a key player in inflammatory responses. In summary, our study demonstrated that curcumin inhibited the activation of NF- κB in the lungs of diabetic rats, thus reducing pulmonary inflammatory responses and oxidative stress, and ultimately relieving diabetes-induced lung injury. This study suggests that curcumin may be a promising agent to alleviate diabetic lung injury and also provides theoretical foundation for the development of diabetes therapy. [ABSTRACT FROM AUTHOR]

Background This study explores the protective effects of a hydrogen sulfide donor, morpholin-4-ium 4-methoxyphenyl-morpholino-phosphinodithioate (GYY4137), in the hearts of diabetic mice that had been subjected to myocardial ischemia/reperfusion injury. Diabetes impairs the Akt pathway, in which the Akt protein is dephosphorylated and inactivated by PH domain leucine-rich repeat protein phosphatase-1 (PHLPP-1). However, the function of PHLPP-1 and molecular mechanism that underlies the cardiac protection exerted by GYY4137 remains unknown. Methods Diabetic or nondiabetic mice were subjected to 45 min of coronary artery occlusion followed by 2 h of reperfusion. H9c2 cells were cultured with normal or high glucose and then subjected to 3 h of hypoxia followed by 6 h of reoxygenation. Pretreatment with GYY4137 was performed in a randomized manner before ischemia/reperfusion or hypoxia/reoxygenation. The infarct size, cardiomyocyte apoptosis, and oxidative stress were measured. Western blotting was conducted to elucidate the protective mechanism. Results Diabetic mice or H9c2 cells exposed to high glucose displayed a larger infarct size, more severe cardiomyocyte apoptosis, lower cell viability, and increased oxidative stress, which were associated with increased levels of PHLPP-1 and reduced levels of p-Akt and nuclear factor-erythroid-2-related factor 2 (Nrf2) protein expression. These changes were prevented/reversed by GYYG4137 pretreatment. At the cellular level, PHLPP-1 siRNA attenuated cellular injury, and this was associated with increased p-Akt and nuclear Nrf2 protein, whereas the decrement of Akt phosphorylation induced by LY294002 augmented cellular injury and decreased nuclear Nrf2. Conclusions GYY4137 activates the PHLPP-1/Akt/Nrf2 pathway to protect against diabetic myocardial ischemia/reperfusion injury. [ABSTRACT FROM AUTHOR]