Project description:Global transcript profiling to identify differentially expressed skeletal muscle genes in insulin resistance, a major risk factor for Type II (non-insulin-dependent) diabetes mellitus. Compared gene expression profiles of skeletal muscle tissues from 18 insulin-sensitive versus 17 insulin-resistant equally obese, non-diabetic Pima Indians. Keywords: other
Project description:We determined the expression profiles in skeletal muscle from people with type 2 diabetes, first degree relatives, and healthy control individuals by microarray experiments. All subjects were Caucasian males and biopsies were taken after a controlled metabolic period of a two hour hyperinsulinemic euglycemic clamp. Our results show for the first time that insulin signaling is significantly downregulated in people with type 2 diabetes, whereas it is significantly upregulated in first degree relatives. Furthermore, we identify several new genes in skeletal muscle from first degree relatives that have an altered gene expression compared to healthy controls.
Project description:Skeletal muscle insulin resistance, an early metabolic defect in the pathogenesis of type 2 diabetes, may be a cause or consequence of altered protein expressions profiles. Proteomics technology offers enormous promise to investigate molecular mechanisms underlying pathologies, however, the analysis of skeletal muscle is challenging. Using a state-of-the-art mass spectrometry (MS) based workflow, we performed a global proteomics analysis of skeletal muscle from leptin-deficient, obese, type 2 diabetic (ob/ob) and lean mice, identifying more than 6,000 proteins with 118 proteins differentially regulated in obesity. This included protein kinases, phosphatases, and secreted and fiber type associated proteins. Enzymes involved in lipid metabolism in skeletal muscle from ob/ob mice were increased, providing evidence against reduced fatty acid oxidation in lipid-induced insulin resistance. Mitochondrial and peroxisomal proteins, as well as components of pyruvate and lactate metabolism were likewise increased. Finally, the skeletal muscle proteome from ob/ob mice displayed a shift towards the ‘slow fiber type’. This detailed characterization of obese rodent models of type 2 diabetes demonstrates an efficient workflow for skeletal muscle proteomics, which may easily be adapted to other complex tissues.
Project description:The current study aimed to address the hypothesis that programmed expression of key miRNAs in skeletal muscle mediates the development of insulin resistance, and consequently long-term health. We thus examined microRNA signatures in skeletal muscle of unmedicated newly diagnosed human pre-diabetics and type 2 diabetics. Skeletal muscle biopsies were obtained from the vastus lateralis from males with pre-diabetes (PD, n=5) or type 2 diabetes mellitus (T2DM, n=6) along with age and sex-matched healthy volunteers (H, n=5). Ramaciotti Centre for Genomics (UNSW, sydney, Australia)
Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion. Global gene expression profile of normal dermal lymphatic endothelial cells (ndLECs) compared to dermal lymphatic endothelial cells derived from type 2 diabetic patients (dLECs).Quadruplicate biological samples were analyzed from human lymphatic endothelial cells (4 x diabetic; 4 x non-diabetic). subsets: 1 disease state set (dLECs), 1 control set (ndLECs)
Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion.