Effect of SSHE on the features of apoptosis in Panc-1 cells

old-change > 1.5 are shown in the heat maps and are clustered by hierarchical clustering. Heat maps of gene expression comparing sedentary vs. treadmill in gastrocnemius of WT samples. Highly overrepresented Gene Ontology categories suggest that the immediate response to exhaustive exercise in exercise nave mice is to initiate the development of vascular system changes that may offer physiological adaption to the exercise. In the CD38 KO HFHSD samples, on the other hand, 146 gene transcripts were significantly altered after the completion of treadmill running comparing with the rested state. The 147 and 146 altered gene transcripts in WT and KO HFHSD samples were combined and resulted in 215 unique gene transcripts. The expression heatmap of these 215 gene transcripts 11 / 19 CD38 and Exercise Intolerance and Metabolic Inflexibility demonstrated that the dis-regulation patterns caused by treadmill running of these genes are essentially identical in WT and PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19722344 CD38 KO HFHSD samples. This suggests that the loss of CD38 has very little impact on the immediate early transcriptional responses in skeletal muscle to exhaustive exercise. Thus, changes in the transcriptome are IMR 1 biological activity driven by exercise and not significantly modified by genotype. The complete gene expression microarray data of this study is available in GEO with accession number GSE69062. Discussion The loss of CD38 activity either by genetic deletion or through the use of a small molecule inhibitor can protect mice from diet-induced obesity and insulin resistance. Molecularly, this is thought to be mediated by elevated NAD+ levels and a consequent increase in sirtuin deacetylase activity. We demonstrated here that CD38 KO mice on HFHSD displayed lower body weight and a higher respiratory exchange ratio. We did not observe enhanced insulin sensitivity or glucose disposal in contrast with previous report. We report a dramatic improvement in exercise tolerance in the HFHSD fed CD38 KO mice suggesting broadly beneficial effects of the loss of CD38 on whole body exercise tolerance. Why do CD38 KO mice weigh less on a HFHSD It is known that high fat diets can induce a state of catecholamine resistance that impairs the mobilization of stored fat by lipolysis. We observed that CD38 KO mice on a HFHSD do not develop diet-induced catecholamine resistance and thus are likely to preserve the capacity to break down triglyceride stored in fat cells via beta-adrenergic receptor signaling. This suggests that one explanation for the PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19723632 reduced size of the fat depot in CD38 KO HFHSD fed mice is a reduced ability to store lipids and increased peripheral utilization of the fat for energy. Several unique functions of CD38 on regulating diet-induced metabolic inflexibility and exercise intolerance were observed. Healthy skeletal muscle maintains metabolic flexibility allowing a switch between fat and glucose oxidation in response to nutrients. Obesity and insulin resistance are associated with an impaired switch from fat to glucose oxidation after a meal. During prolonged submaximal, fixed intensity exercise lipids are consumed preferentially to carbohydrates. The increased reliance on fat oxidation is to presumably delay the consumption of muscle glycogen. Individuals with obesity or type II diabetes exhibit metabolic inflexibility, which can further affect muscle performance. Loss of CD38 preserved glucose oxidation after a meal and prolonged fat oxidation during the exercise test. This may be linked to the appa