Insulin glucose-stimulated

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. 

Metformin restrains hepatic glucose production principally by suppression of gluconeogenesis. The mechanisms involve potentiation of insulin action and decreased hepatic extraction of certain gluconeogenic substrates such as lactate. In addition, metformin reduces the rate of hepatic glycogenolysis and decreases the activity of hepatic glucose-6-phosphatase. Insulin-stimulated glucose uptake and glycogenesis by skeletal muscle is increased by metformin mainly by increased... 

The sulfonylureas appear to lower blood glucose by stimulating the beta cells of the pancreas to release insulin. The sulfonylureas are not effective if the beta cells of the pancreas are unable to release a sufficient amount of insulin to meet the individual s needs. The first generation sulfonylureas (eg, chlorpropamide, tolazamide, and tolbutamide) are not commonly used today because they have a long duration of action and a higher incidence of adverse... 

GLUT 4 Heart and skeletal muscle, adipose tissue Insulin-stimulated uptake of glucose... 

Insulin stimulates lipogenesis by several other mechanisms as well as by increasing acetyl-CoA carboxylase activity. It increases the transport of glucose into the cell (eg, in adipose tissue), increasing the availability of both pyruvate for fatty acid synthesis and glycerol 3-phosphate for esterification of the newly formed fatty acids, and also converts the inactive form of pyruvate dehydrogenase to the active form in adipose tissue but not in liver. Insulin also—by its ability to depress the level of intracellular cAMP—inhibits lipolysis in adipose tissue and thereby reduces the concentration of... 

Carayannopoulos, M. O., et al. GLUT8 is a glucose transporter responsible for insulin-stimulated glucose uptake in the blastocyst. Proc. Natl. Acad. Sci. U. S. A. 2000, 97, 7313-7318. 

Cheatham, B., Vlahos, C. J., Cheatham, L., Wang, L., Blenis, J., and Kahn, C. R. (1994). Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol. Cell. Biol. 14, 4902-4911. 

It was discovered nearly 20 years ago that V(V) as vanadate and V(IV) as vanadyl can mimic some of the effects of insulin (stimulate glucose uptake and oxidation and glycogen synthesis) (512, 513). Vanadate is an effective insulin mimetic in the diabetic rat (514), but has proved to be too toxic for human use. Vanadyl, as VOS04, is also unsuitable because high doses are needed on account of its poor oral absorption. Vanadium complexes with organic ligands have proved to be less toxic and can have improved aqueous solubility and lipophil-icity. 

GLUT 4 Skeletal muscle Adipose tissue 5 mM Insulin-stimulated glucose uptake... 

To gain further insight into the mechanisms involved in defective insulin-stimulated glucose uptake in skeletal muscle of insulin-resistant subjects, the possible role of IMCL in the pathogenesis of skeletal muscle insulin resistance and type 2 diabetes mellitus was explored by comparing insulin sensitivity (GIR) and IMCL content of insulin-resistant and insulin-sensitive offsprings of patients with type 2 diabetes. Twenty-six healthy subjects were included in the first study, 13 of them classified as insulin-sensitive and further 13 as insulin-resistant. Metabolic and anthropometric data are given in Table 4. 

Glutamine, along with glucose, can stimulate insulin secretion by the endocrine pancreas. The significance of this is the regulation of the plasma glutamine concentration is not known. 

Changes in the blood levels of these hormones all contribute to regulation of blood glncose level in several conditions. After a meal glucose utilisation is increased, since insulin stimulates glucose uptake by muscle and inhibits release of fatty acids from adipose tissue. Physical activity... 

Figure 12.18 Sites at which insulin stimulates glycogen synthesis in muscle. An increase in the blood glucose level, after a meal, increases secretion of insulin from the p-cells in the Islets of Langerhans. Insulin increases the transport of glucose into the muscle fibre and the activity of glycogen synthase (Chapter 6). The result is that insulin increases the rate of glycogen synthesis without marked changes in concentrations of glucose 6-phos-phate, glucose 1-phosphate or UDP-glucose in the liver.

The lipid metabolism of adipose tissue is also influenced by the hormone. In these cells, insulin stimulates the reorganization of glucose into fatty acids. This is mainly based on activation of acetyl CoA carboxylase (see p. 162) and increased availability of NADPH+H due to increased PPP activity (see p. 152). On the other hand, insulin also inhibits the degradation of fat by hormone-... 

Jordan SD, Kruger M, Willmes DM et al (2011) Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism. Nat CeU Biol 13 434-446... 

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