Insulin glucose uptake

The complex thioamide lolrestat (8) is an inhibitor of aldose reductase. This enzyme catalyzes the reduction of glucose to sorbitol. The enzyme is not very active, but in diabetic individuals where blood glucose levels can. spike to quite high levels in tissues where insulin is not required for glucose uptake (nerve, kidney, retina and lens) sorbitol is formed by the action of aldose reductase and contributes to diabetic complications very prominent among which are eye problems (diabetic retinopathy). Tolrestat is intended for oral administration to prevent this. One of its syntheses proceeds by conversion of 6-methoxy-5-(trifluoroniethyl)naphthalene-l-carboxyl-ic acid (6) to its acid chloride followed by carboxamide formation (7) with methyl N-methyl sarcosinate. Reaction of amide 7 with phosphorous pentasulfide produces the methyl ester thioamide which, on treatment with KOH, hydrolyzes to tolrestat (8) 2[. 

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... 

Antidiabetic Drugs other than Insulin. Figure 3 The antihyperglycaemic effect of metformin involves enhanced insulin-mediated suppression of hepatic glucose production and muscle glucose uptake. Metformin also exerts non-insulin-dependent effects on these tissues, including reduced fatty acid oxidation and increased anaerobic glucose metabolism by the intestine. FA, fatty acid f, increase i decrease. 

There is weak expression of PPARy in muscle, liver and other tissues, enabling TZDs to support the effects of insulin in these tissues, notably increased glucose uptake in muscle and reduced glucose production in liver. TZDs may also affect nutrient metabolism by skeletal muscle through a direct mitochondrial action that is independent of PPARy. 

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... 

The exact mechanism by which PPARy ligands affect insulin resistance (improved glucose uptake by peripheral tissues, most notably skeletal muscle) remains unclear. 

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

Shikonm stimulates glucose uptake in 3T3-L1 adipocytes via an insulin-independent tyrosine kinase pathway. Biochem. Biophys Res Commun. 292 (3) 642-51. 

Thiazolidinediones are known to increase insulin sensitivity by stimulating peroxisome proliferator-activated receptor gamma (PPAR-y). Stimulation of PPAR-y results in a number of intracellular and extracellular changes, including an increased number of insulin receptors, increased insulin receptor sensitivity, decreased plasma fatty acid levels, and an increase in a host of intracellular signaling proteins that enhance glucose uptake. 

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. 

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. 

The promotion by insulin of glucose uptake by muscle and fat cells (adipocytes), of glycogen deposition in liver and muscle, and its stimulation of growth soon emerged as the purified hormone became available for study. Although insulin was crystallized by Abel in 1926, its primary structure established by Sanger in 1953 (see Chapter 10),... 

Answer C. Insulin increases glucose transport in only two tissues, adipose and muscle. The major site of glucose uptake is muscle, which decreases hyperglycemia. Glucose and ketone transport and metabolism are insulin independent in the brain (choice D). Insulin would slow gluconeogenesis (choice A) and fatty acid release from adipose (choice B). Insulin would inhibit glycogenolysis in the liver (choice E). 

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

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