Evidence for the cell surface locus of presynaptic purine nucleotide receptors in the guinea-pig ileum

We examined the hypothesis that insulin resistance in skeletal muscle promotes the development of atherogenic dyslipidemia, associated with the metabolic syndrome, by altering the distribu-tion pattern of postprandial energy storage. Following ingestion of two high carbohydrate mixed meals, net muscle glycogen synthe-sis was reduced by Ϸ60% in young, lean, insulin-resistant subjects compared with a similar cohort of age–weight– body mass index– activity-matched, insulin-sensitive, control subjects. In contrast, hepatic de novo lipogenesis and hepatic triglyceride synthesis were both increased by \textgreater2-fold in the insulin-resistant subjects. These changes were associated with a 60% increase in plasma triglyceride concentrations and an Ϸ20% reduction in plasma high-density lipoprotein concentrations but no differences in plasma concentrations of TNF-␣, IL-6, adiponectin, resistin, retinol binding protein-4, or intraabdominal fat volume. These data dem-onstrate that insulin resistance in skeletal muscle, due to decreased muscle glycogen synthesis, can promote atherogenic dyslipidemia by changing the pattern of ingested carbohydrate away from skeletal muscle glycogen synthesis into hepatic de novo lipogen-esis, resulting in an increase in plasma triglyceride concentrations and a reduction in plasma high-density lipoprotein concentrations. Furthermore, insulin resistance in these subjects was independent of changes in the plasma concentrations of TNF-␣, IL-6, high-molecular-weight adiponectin, resistin, retinol binding protein-4, or intraabdominal obesity, suggesting that these factors do not play a primary role in causing insulin resistance in the early stages of the metabolic syndrome.