The expression of TNF alpha by human muscle. Relationship to insulin resistance.

Abstract

TNF ␣ is overexpressed in the adipose tissue of obese rodents and humans, and is associated with insulin resistance. To more closely link TNF expression with whole body insulin action, we examined the expression of TNF by muscle, which is responsible for the majority of glucose uptake in vivo. Using RT-PCR, TNF was detected in human heart, in skeletal muscle from humans and rats, and in cultured human myocytes. Using competitive RT-PCR, TNF was quantitated in the muscle biopsy specimens from 15 subjects whose insulin sensitivity had been characterized using the glucose clamp technique. TNF expression in the insulin resistant subjects and the diabetic patients was fourfold higher than in the insulin sensitive subjects, and there was a significant inverse linear relationship between maximal glucose disposal rate and muscle TNF ( r ϭ Ϫ 0.60, P Ͻ 0.02). In nine subjects, muscle cells from vastus lateralis muscle biopsies were placed into tissue culture for 4 wk, and induced to differentiate into myotubes. TNF was secreted into the medium from these cells, and cells from diabetic patients expressed threefold more TNF than cells from nondiabetic subjects. Thus, TNF is expressed in human muscle, and is expressed at a higher level in the muscle tissue and in the cultured muscle cells from insulin resistant and diabetic subjects. These data suggest another mechanism by which TNF may play an important role in human insulin resistance. (

Hypoadiponectinemia in Obesity: Association with Insulin Resistance

“…In numerous obesity-diabetes models, tumor necrosis factor-a over expressed in adipose and muscle tissues and tumor necrosis factor-a blocks the action of insulin in cultured cells [26]. In humans, tumor necrosis factor-a also over expressed in the adipose and muscle tissues of obese insulin resistance subjects [27]. The production and action of tumor necrosis factor-a, both has been shown to inhibit by adiponectin [28].…”

Task-oriented treadmill exercise training in chronic hemiparetic stroke

“…Furthermore, nearly threefold elevated levels of tumor necrosis factor-α (TNF-α) messenger RNA are reported in hemiparetic quadriceps muscle from patients with stroke compared with those from nonparetic legs and nonstroke control subjects [34]. Elevated TNF-α levels in skeletal muscle tissue are strongly linked to muscular wasting and insulin resistance in T2DM and advancing age and may contribute to the structural and metabolic abnormalities in hemiparetic skeletal muscle after stroke [35][36][37][38]. Since exercise training has been shown to reduce skeletal muscle TNF-α expression, which improves muscle strength and metabolic function in selected nonstroke populations [36], modification of inflammatory pathways through exercise therapy warrants consideration in the high CVD risk stroke population.…”

Expression of anti-inflammatory macrophage genes within skeletal muscle correlates with insulin sensitivity in human obesity and type 2 diabetes

“…Muscle-infiltrating macrophages in obesity might affect muscle glucose metabolism via secreted factors that impair glucose homeostasis. Although the rise in human muscle inflammatory genes in obesity and type 2 diabetes correlates with insulin resistance [5], evidence for elevated immune cells in human muscle in obesity and type 2 diabetes is scant and controversial [6,7]. Moreover, the phenotypic polarisation of muscle macrophages in obesity and type 2 diabetes is unknown, as is any possible correlation to metabolic status.…”