The recent report of the Adult Treatment Panel (ATP III) of the National Cholesterol Education Program (1) identified as cardiovascular disease (CVD) risk factors what they referred to as a “constellation of lipid and nonlipid risk factors of metabolic origin,” indicated that “this syndrome is closely related to insulin resistance,” and proposed diagnostic criteria for what they designated as “...

Glycogen synthase kinase-3 (GSK3) has been implicated in the multifactorial etiology of skeletal muscle insulin resistance in animal models and in human type 2 diabetic subjects. However, the potential molecular mechanisms involved are not yet fully understood. Therefore, we determined if selective GSK3 inhibition in vitro leads to an improvement in insulin action on glucose transport activity ...

Insulin resistance, a critical component of type 2 diabetes (T2D), precedes and predicts T2D onset. T2D is also associated with mitochondrial dysfunction. To define the cause-effect relationship between insulin resistance and mitochondrial dysfunction, we compared mitochondrial metabolism in induced pluripotent stem cells (iPSC) from 5 healthy individuals and 4 patients with genetic insulin res...

Insulin resistance is instrumental in the pathogenesis of type 2 diabetes mellitus and the Insulin Resistance Syndrome. While insulin resistance involves decreased glucose transport activity in skeletal muscle, its molecular basis is unknown. Since muscle GLUT4 glucose transporter levels are normal in type 2 diabetes, we have tested the hypothesis that insulin resistance is due to impaired tran...

OBJECTIVE Whereas insulin resistance is expressed as reduced glucose uptake in peripheral tissues, the relationship between and brain metabolism remains controversial. Our aim was to examine association of (BGU) during a euglycemic hyperinsulinemic clamp large sample study participants across wide range age sensitivity. RESEARCH DESIGN AND METHODS [18F]-fluorodeoxyglucose positron emission tomo...

UNLABELLED Insulin binding to isolated adipocytes from 16 normal and 14 obese patients was studied. The data indicated that, as a group, adipocytes from the obese patients bound significantly less insulin than normal. However, of the 14 obese patients, 5 were not hyperinsulinemic and 4 of these 5 subjects had normal insulin binding. These subjects were also younger, and had the onset of obesity...

In insulin-resistant states (obesity, pre-diabetes, and type 2 diabetes), hepatic production of glucose and lipid synthesis are heightened in concert, implying that insulin deficiency and insulin excess coexists in this setting. The fact that insulin may be inadequate or excessive at any one point in differing organs and tissues has many biologic ramifications. In this context the concept of me...

We thank Drs. Lieske and Birkenfeld (1) for their comments. We agree that in our article (2) we did not address the question of whether or not the activating effects of insulin on endoplasmic reticulum (ER) stress will become resistant in the setting of obesity-associated insulin resistance and that it would be important to understand whether or not insulin-resistant humans remain sensitive to ...