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The AMP-activated protein kinase (AMPK) is a critical regulator of energy balance at both the cellular and whole-body levels. Two upstream kinases have been reported to activate AMPK in cell-free assays, i.e., the tumor suppressor LKB1 and calmodulin-dependent protein kinase kinase. However, evidence that this is physiologically relevant currently only(More)
The AMP-activated protein kinase is a sensor of cellular energy status that is found in all eukaryotic cells. It is activated by rising AMP and falling ATP by a complex mechanism that results in an ultrasensitive response. The functions of the different domains on the three subunits of the alphabetagamma heterotrimer are slowly being unravelled, and a(More)
BACKGROUND Insulin resistance and hyperinsulinemia are features of obesity, non-insulin-dependent diabetes mellitus, and other disorders. Skeletal muscle is a major site of insulin action, and insulin sensitivity may be related to the fatty-acid composition of the phospholipids within the muscle membranes involved in the action of insulin. METHODS We(More)
The AMP-activated protein kinase (AMPK) is a sensor of cellular energy charge and a 'metabolic master switch'. When activated by ATP depletion, it switches off ATP-consuming processes, while switching on catabolic pathways that generate ATP. AMPK exists as heterotrimeric complexes comprising catalytic alpha subunits and regulatory beta and gamma subunits,(More)
This report examines the effect of polyunsaturated fatty acids (PUFA) on lipogenic gene expression in cultured 3T3-L1 adipocytes. Arachidonic acid (20:4, n-6) and eicosapentaenoic acid (20:5, n-3) suppressed mRNAs encoding fatty acid synthase (FAS) and S14, but had no effect on beta-actin. Using a clonal adipocyte cell line containing a stably integrated(More)
In animal studies, increased amounts of triglyceride associated with skeletal muscle (mTG) correlate with reduced skeletal muscle and whole body insulin action. The aim of this study was to test this relationship in humans. Subjects were 38 nondiabetic male Pima Indians (mean age 28 +/- 1 years). Insulin sensitivity at physiological (M) and(More)
The cellular basis of insulin resistance is still unknown; however, relationships have been demonstrated between insulin action in muscle and the fatty acid profile of the major membrane structural lipid (phospholipid). The present study aimed to further investigate the hypothesis that insulin action and adiposity are associated with changes in the(More)
Insulin resistance in skeletal muscle is associated with 1) relative increases in the proportion of glycolytic and fast-twitch muscle fibers and decreases in the proportion of more oxidative fibers and 2) a higher proportion of the saturated fatty acids in membrane structural lipids. Exercise is known to improve insulin action. The aims of the current(More)
In the present study, the time course of change in sucrose-induced insulin resistance, triglyceride (TG) concentration, and liver fatty acid composition was examined. Male rats (n = 8-10/group per time point) was fed a high-starch (ST) diet for 2 wk and were then equicalorically fed ST or a high-sucrose (SU) diet for 1, 2, 5, or 8 wk. Body weight and(More)
The purpose of the present study was to compare tissue oxidative capacity, skeletal muscle fatty acid composition, and tissue fuel stores in low-fat fed (LFD, 12% of energy from corn oil) male Wistar rats, and in high-fat fed (45% of energy from corn oil) obesity-prone (OP) and obesity-resistant (OR) male Wistar rats. Designation of OP and OR rats was based(More)