Insulin tissue sensitivity

Rossetti L, Smith D, Shuhnan GI, Papachristou D, DeFronzo RA. (1987) Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest 79 1510-1515. 

Finally, insulin resistance is present in disease states other than type 2 diabetes mellitus. Patients with conditions such as hypertension, obesity, and certain hyperlipidemias are also found to have decreased tissue sensitivity to circulating insulin.19,72 As discussed in Chapter 21, a combination of these abnormalities is often described as metabolic syndrome, or syndrome X.127,128 Metabolic syndrome occurs when insulin resistance, high blood pressure, abdominal... 

May involve T tissue sensitivity to insulin and/or 4- hepatic gluconeogenesis (Figure VII-2-2). 

Metformin enhances tissue sensitivity to insulin and inhibits liver gluconeogenesis. The potential adverse effect is lactic acidosis. 

Glipizide is a sulfonylurea that decreases blood glucose by stimulating insulin release from pancreas and by increasing tissue sensitivity to insulin. It is indicated as an adjunct to diet to lower blood glucose in patients with non-insulin-dependent diabetes mellitus (type 2) whose hyperglycemia cannot be controlled by diet alone. 

The absorption of sulfonylureas from the upper gastrointestinal tract is faidy rapid and complete. The agents are transported in the blood as protein-bound complexes. As they are released from protein-binding sites, the free (unbound) form becomes available for diffusion into tissues and to sites of action. Specific receptors are present on pancreatic islet P-ceU surfaces which bind sulfonylureas with high affinity. Binding of sulfonylureas to these receptors appears to be coupled to an ATP-sensitive channel to stimulate insulin secretion. These agents may also potentiate insulin-stimulated glucose transport in adipose tissue and skeletal muscle. 

The first hormonal signal found to comply with the characteristics of both a satiety and an adiposity signal was insulin [1]. Insulin levels reflect substrate (carbohydrate) intake and stores, as they rise with blood glucose levels and fall with starvation. In addition, they may reflect the size of adipose stores, because a fatter person secretes more insulin than a lean individual in response to a given increase of blood glucose. This increased insulin secretion in obesity can be explained by the reduced insulin sensitivity of liver, muscle, and adipose tissue. Insulin is known to enter the brain, and direct administration of insulin to the brain reduces food intake. The adipostatic role of insulin is supported by the observation that mutant mice lacking the neuronal insulin receptor (NDRKO mice) develop obesity. 

GLUT4 is a glucose transporter exclusively expressed in tissues with insulin-sensitive glucose uptake (heart, muscle, fat). Under basal conditions, GLUT4 is predominantly located in intracellular vesicles, and is... 

Altered expression and secretion of adipose tissue-derived factors thought to affect insulin sensitivity adiponectin, TNF-a, IL-6, etc. t Insulin sensitivity and glucose-lowering... 

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