Lawrence J. Mandarino

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OBJECTIVE Insulin resistance in skeletal muscle is an early phenomenon in the pathogenesis of type 2 diabetes. Studies of insulin resistance usually are highly focused. However, approaches that give a more global picture of abnormalities in insulin resistance are useful in pointing out new directions for research. In previous studies, gene expression(More)
PURPOSE To characterize the properties of the glucose transporters of bovine retinal capillary endothelial cells and pericytes and to determine the effects of increased glucose concentrations on glucose transport activity. METHODS Primary cultures of bovine retinal capillary endothelial cells and pericytes were exposed to low and high glucose(More)
OBJECTIVE The contribution of mitochondrial dysfunction to skeletal muscle insulin resistance remains elusive. Comparative proteomics are being applied to generate new hypotheses in human biology and were applied here to isolated mitochondria to identify novel changes in mitochondrial protein abundance present in insulin-resistant muscle. RESEARCH DESIGN(More)
OBJECTIVE Aging increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes. It has been proposed that increased reactive oxygen species (ROS) generation by dysfunctional mitochondria could play a role in the pathogenesis of these metabolic abnormalities. We examined whether aging per se (in subjects with normal glucose tolerance(More)
The widely occurring tetradecapeptide somatostatin (SRIF-14) has been variously implicated as a neurotransmitter, a neurohormone, a cybernin (local regulatory factor) and a hormone. In the first isolation of SRIF-14 from hypothalamic extracts and subsequent extracts of other tissues, peptides of higher molecular weight but with similar activity have been(More)
The rising prevalence of gestational diabetes mellitus (GDM) affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying(More)
This study was undertaken to test the hypothesis that short-term exposure (4 h) to physiological hyperinsulinemia in normal, healthy subjects without a family history of diabetes would induce a low grade inflammatory response independently of glycemic status. Twelve normal glucose tolerant subjects received a 4-h euglycemic hyperinsulinemic clamp with(More)
Changes in protein abundance in skeletal muscle are central to a large number of metabolic and other disorders, including, and perhaps most commonly, insulin resistance. Proteomics analysis of human muscle is an important approach for gaining insight into the biochemical basis for normal and pathophysiological conditions. However , to date, the number of(More)
BACKGROUND Healthy individuals on the lower end of the insulin sensitivity spectrum also have a reduced gene expression response to exercise for specific genes. The goal of this study was to determine the relationship between insulin sensitivity and exercise-induced gene expression in an unbiased, global manner. METHODS AND FINDINGS Euglycemic clamps were(More)
The phosphorylation of glucose to glucose-6-phosphate, catalyzed by hexokinase, is the first committed step in glucose uptake into skeletal muscle. Two isoforms of hexokinase, HKI and HKII, are expressed in human skeletal muscle, but only HKII expression is regulated by insulin. HKII messenger RNA, protein, and activity are increased after 4 h of insulin(More)