Search

OBJECTIVE--The incidence of posttransplantation diabetes mellitus (PTDM) has been reported to vary according to different study populations or different definitions. In this study, using American Diabetes Association criteria, the incidence [...]

Aging is associated with mitochondrial dysfunction, which leads to a decline in cellular function and the development of age-related diseases. Reduced skeletal muscle mass with aging appears to promote a decrease in mitochondrial quality and quantity. Moreover, mitochondrial dysfunction adversely affects the quality and quantity of skeletal muscle. During aging, physical exercise can cause beneficial adaptations to cellular energy metabolism in skeletal muscle, including alterations to mitochondrial content, protein, and biogenesis. Here, we briefly summarize current findings on the association between the aging process and impairment of mitochondrial function, including mitochondrial biogenesis and reactive oxygen species in skeletal muscle. We also discuss the potential role of exercise in the improvement of aging-driven mitochondrial dysfunctions.

ABSTRACTBackground: Ginsenoside Rg3 has been proposed to mediate anti-diabetic effects, but their direct effect on pancreatic β cell viability and mechanisms are not clearly understood. Recent studies suggest that intermittent high glucose (IHG) could be more harmful to pancreatic β cells than sustained high glucose. There are few reports about the effect of the ginsenosideRg3 to β cell apoptosis and proliferation against IHG.Methods: INS-1 cells were treated with alternative glucose concentration with or without ginsenoside Rg3. Cell apoptosis and viability were detected by Annexin V staining and MTT assay. The activation of mitogen-activated protein kinases (MAPKs) was analyzed by Western blotting using specific antibodies. Quantification of secreted insulin protein was measured using rat/mouse Insulin ELISA kits. Bromodeoxyuridine (BrdU) staining and florescence in situhybridization (FISH) analysis was performed to compare cell proliferation.Result: INS-1 cell viability was decreased under IHG and increased with Rg3 treatment.Rg3 significantly reduced the apoptotic INS-1 cells against IHG. The quantification of secreted insulin concentration was increased with Rg3. Rg3 increased INS-1 cell proliferation. ERK and p38 MAPK pathways reduced by IHG were activated by the ginsenoside Rg3.Conclusion: Ginsenoside Rg3 protected INS-1 cell death from IHG with reducing apoptosis and increasing proliferation.

The divalent zinc ion is a cation that plays an indispensable role as a structural constituent of numerous proteins, including enzymes and transcription factors. Recently, it has been suggested that zinc also plays a dynamic role in extracellular and intracellular signaling as well. Ion channels are pore-forming proteins that control the flow of specific ions across the membrane, which is important to maintain ion gradients. In this review, we outline the modulatory effect of zinc on the activities of several ion channels through direct binding of zinc into histidine, cysteine, aspartate, and glutamate moieties of channel proteins. The binding of zinc to ion channels results in the activation or inhibition of the channel due to conformational changes. These novel aspects of ion-channel activity modulation by zinc provide new insights into the physiological regulation of ion channels.

Gastrin increases the growth and neogenesis of the islets of Langerhans. Oral proton pump inhibitors (PPIs) increase the circulating gastrin level in animals and humans, but the therapeutic benefit of PPIs for diabetes mellitus has not been resolved. We examined whether treatment with a PPI for ≥2 months affected the glycated hemoglobin (A1C) level in patients with type 2 diabetes.

The aim of this review was to understand the effects of β-adrenergic stimulation on oxidative stress, structural remodeling, and functional alterations in the heart and cerebral artery. Diverse stimuli activate the sympathetic nervous system, leading to increased levels of catecholamines. Long-term overstimulation of the β-adrenergic receptor (βAR) in response to catecholamines causes cardiovascular diseases, including cardiac hypertrophy, stroke, coronary artery disease, and heart failure. Although catecholamines have identical sites of action in the heart and cerebral artery, the structural and functional modifications differentially activate intracellular signaling cascades. βAR-stimulation can increase oxidative stress in the heart and cerebral artery, but has also been shown to induce different cytoskeletal and functional modifications by modulating various components of the βAR signal transduction pathways. Stimulation of βAR leads to cardiac dysfunction due to an overload of intracellular Ca2+in cardiomyocytes. However, this stimulation induces vascular dysfunction through disruption of actin cytoskeleton in vascular smooth muscle cells. Many studies have shown that excessive concentrations of catecholamines during stressful conditions can produce coronary spasms or arrhythmias by inducing Ca2+-handling abnormalities and impairing energy production in mitochondria, In this article, we highlight the different fates caused by excessive oxidative stress and disruptions in the cytoskeletal proteome network in the heart and the cerebral artery in responsed to prolonged βAR-stimulation.

A growing body of evidence suggests that exercise may contribute to preventing pathological changes, treating multiple chronic diseases, and reducing mortality and morbidity ratios. Scientific evidence moreover shows that exercise plays a key role in improving health-related physical fitness components and hormone function. Regular exercise training is one of the few strategies that has been strictly adapted in healthy individuals and in athletes. However, time-dependent exercise has different outcomes, based on the exercise type, duration, and hormone adaptation. In the present review, we therefore briefly describe the type, duration, and adaptation of exercise performed in the morning and evening. In addition, we discuss the clinical considerations and indications for exercise training.

Medicinal tablets have been used for a long time to treat cardiovascular disease. However, mortality rate is steadily increasing partly because of the patients’ sedentary lifestyle and unhealthy diet. By contrast, exercise has been systematically shown to have multiple benefits. Regular exercise training can prevent various diseases in healthy individuals. Combined exercise and cardiac medications may lead to the improvement of heart disease. Numerous exercise training pathways still need further investigations. How exercise can prevent, treat, or attenuate diseases remains somewhat elusive. Thus, this review will discuss cardiac medications in parallel with the mechanism of action of exercise.

The objectives of this study were to identify the genetic variants of CYP2C8, analyze CYP2C8 single nucleotide polymorphisms (SNPs), and characterize their functional consequences in the CYP2C8 substrate drug rosiglitazone in humans. The direct full sequencing of CYP2C8 genomic DNA was performed in a Korean population (n = 50). A total of 17 CYP2C8 variants including a novel coding variant (E274Stop) were identified. The novel CYP2C8 E274Stop variant was assigned as CYP2C8*11 by the Human Cytochrome P450 (CYP) Allele Nomenclature Committee. Seventeen SNPs were used to characterize linkage disequilibrium, haplotype structures, and haplotype tagging SNPs. Genotyping for CYP2C8*11 in an extended set of Koreans (n = 400), whites (n = 100), Han Chinese (n = 348), Vietnamese (n = 100), and African Americans (n = 93) was performed by a newly developed pyrosequencing method. The frequency of CYP2C8*11 was 0.3% in Koreans, 1% in Vietnamese, and 0.14% in Chinese. However, none of the whites or African Americans contained the CYP2C8*11 allele. Subjects with CYP2C8*1/*11 exhibited higher plasma concentration-time profiles of rosiglitazone than those of nine control subjects carrying CYP2C8*1/*1. The area under the concentration-time curve and peak plasma concentration of rosiglitazone in individuals carrying CYP2C8*1/*11 (n = 5) were 54 and 34% higher than the mean values observed in the control subjects carrying CYP2C8*1/*1 (P = 0.015 and P = 0.025, respectively). In summary, this is the first report to characterize the allele frequency and haplotype distribution of CYP2C8 in a Korean population, and it provides functional analysis of a new variant CYP2C8*11. Our findings suggest that individuals carrying CYP2C8*11, a null allele found in Asians only, may have lower activity for metabolizing CYP2C8 substrate drugs.

Bortezomib is a proteasome inhibitor used for the treatment of relapsed/refractory multiple myeloma (MM). However, intrinsic and acquired resistance to bortezomib has already been observed in MM patients. In a previous report, we demonstrated that changes in the expression of mitochondrial genes lead to changes in mitochondrial activity and bortezomib susceptibility or resistance, and their combined effects contribute to the differential sensitivity or resistance of MM cells to bortezomib. Here we report that the combination treatment of bortezomib and 2-methoxyestradiol (2ME), a natural estrogen metabolite, induces mitochondria-mediated apoptotic cell death of bortezomib-resistant MM KMS20 cells via mitochondrial reactive oxygen species (ROS) overproduction. Bortezomib plus 2ME treatment induces a higher level of cell death compared with treatment with bortezomib alone and increases mitochondrial ROS and Ca2+levels in KMS20 cells. Pretreatment with the antioxidant N-acetyl-L-cysteine scavenges mitochondrial ROS and decreases cell death after treatment with bortezomib plus 2ME in KMS20 cells. Moreover, we observed that treatment with bortezomib plus 2ME maintains the activation of c-Jun N-terminal kinase (JNK) and mitogen-activated protein kinase kinase kinase 4/7 (MKK4/7). Collectively, combination treatment with bortezomib and 2ME induces cell death via JNK-MKK4/7 activation by overproduction of mitochondrial ROS. Therefore, combination therapy with specific mitochondrial-targeting drugs may prove useful to the development of novel strategies for the treatment of bortezomib-resistant MM patients.