Adipose tissue insulin affecting

In adipose tissues, insulin accelerates the dissimilation of glucose to CO2 through the Embden-Meyerhof pathway and the hexose monophosphate shunt and increases its utilization for glycogen and fatty acid synthesis. Insulin is without effect on fatty acid uptake and lipogenesis when glucose is absent from the medium. And the studies of Fain and Loken [132] have established that the antilipolytic effect of insulin is blocked by trypsin. Trypsin does not affect its inhibition through other metabolic interferences. A protein factor, possibly a receptor, probably is needed for insulin s action on adipose tissue. 

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... 

Fatty acids are synthesized by an extramitochondrial system, which is responsible for the complete synthesis of palmitate from acetyl-CoA in the cytosol. In the rat, the pathway is well represented in adipose tissue and liver, whereas in humans adipose tissue may not be an important site, and liver has only low activity. In birds, lipogenesis is confined to the liver, where it is particularly important in providing lipids for egg formation. In most mammals, glucose is the primary substrate for lipogenesis, but in ruminants it is acetate, the main fuel molecule produced by the diet. Critical diseases of the pathway have not been reported in humans. However, inhibition of lipogenesis occurs in type 1 (insulin-de-pendent) diabetes mellitus, and variations in its activity may affect the nature and extent of obesity. 

The metabolic abnormalities of diabetes mellitus result from a deficiency of insulin and a relative excess of glucagon. These aberrant hormonal levels most profoundly affect metabolism in three tissues liver, muscle, and adipose tissue (Figure 25.3). 

In detail, adipocytes from visceral adipose tissue are more resistant to insuhn-induced anti-lipolysis and re-esterification of NEFA than those from leg and non-visceral body fat both in vitro [503, 504] and in vivo [505]. Various functional differences in these ceUs have been identified at the level of the insuhn receptor and the post-receptor insulin signahng cascade [503, 504]. PDE3B involved in hpolysis regulation by insuhn (see above. Fig. 11.7) and protein tyrosine phosphatases de-phosphorylating fhe insuhn receptor, such as PTPlb, could be affected in differen-... 

Although the effects of insulin on postprandial metabolism are profound, other factors (e.g., substrate supply and allosteric effectors) also affect the rate and degree to which these processes occur. For example, elevated levels of fatty acids in blood promote lipogenesis in adipose tissue. Regulation by several allosteric effectors further ensures that competing pathways do not occur simultaneously for example, in many cell types fatty acid synthesis is promoted by citrate (an activator of acetyl-CoA carboxylase), whereas fatty acid oxidation is depressed by malonyl-CoA (an inhibitor of carnitine acyltransferase I activity). The control of fatty acid metabolism is described in Section 12.1. 

Insulin is the principal hormone affecting bitxid glucose levels, and an understanding of its actions is an important prerequisite to the study of diabetes mellitus. Insulin is a small protein synihesi/cd in the beta cells of the islets of Langcrhans of the pancreas. It acts through membrane receptors and its main target tissues arc liver, muscle and adipose tissue. 

Fig. 1. Mechanism of the pleiotropic actions of the thiazolidinediones. Working via the PPAR-y receptor system in adipose tissue, the thiazolidinediones interrupt the pathogenic signaling between the expanded visceral adipose mass in obesity, which leads to improved insulin sensitivity in skeletal muscle and hver, enhanced pancreatic P-cell insulin secretion, and improved vascular endothelial function. The processes affected by the thiazolidinediones include redistribution of adipose stores, reduced circulating levels of FFA, diminished levels and tissue effects of cytokines (TNF-a), and increased circulating levels of the insulin-sensitizing, anti-atherogenic plasma protein adiponectin, which also arises from adipose tissue. The thiazohdinediones have also been shown to have direct effects in muscle and endothelial cells, which is likely to also contribute to some of their pharmacologic activity.

Adipose tissue is viewed not simply as a passive lipid storage depot but instead as a highly active metabolic tissue, which secretes numerous products that affect insulin resistance either through a traditional (circulating) hormonal effect, or through local effects on the adipocyte. The term adipokines has been used to describe the numerous adipocyte secretory proteins, which include TNFa, IL-6, leptin, PAI-1, resistin, and adiponectin. 

Insulin in vitro increases the recovery of glucose carbon in the trichloroacetic acid-precipitable protein of epididymal adipose tissue from fasted rats (Herrera and Renold, 1960 Carruthers and Winegrad, 1961), and also increases the incorporation of glucose carbon into the ribonucleic acid fraction of adipose tissue from fasted rats (Carruthers and Winegrad, 1962). That these latter effects were observed in the presence of unlabeled glycine suggests that the bulk of the incorporation was into the pento.se moiety. When adipo.se ti.ssue from fasted rats is incubated with pyruvate- -C pyruvate carbon is isolated in the ribonucleic acid fraction however, the addition of insulin does not affect this incorporation (Carruthers and Winegrad, 1962). 

---