Insulin adipose tissue metabolism affected

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). 

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. 

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. 

Mice have a much higher metabolic rate and are more sensitive to the adipose tissue reducing effects of CLA than any other species that have been studied. In rat studies, the CLA intake levels were similar to those tested in studies with mice and are much lower than the intake levels studied in the 13-week rat feeding study on Clarinol G-80 (1, 5, and 15%) (5). In most studies, CLA did not significantly affect insulin levels in lean rat models (17, 18). As discussed before in the sub-chronic toxicity study, increased insulin levels were found in rats fed 15% CLA only and were likely due to a nutritional imbalance (5). 

Insulin a polypeptide hormone, M, 5,780 (bovine), synthesized in, and secreted by, the B cells of the islets of Langerhans. The first protein primary sequence ever to be elucidated was that of I. (Fig.l) [F. Sanger etal. Biochem. J. 59 (1955) 509-518], I. is the only hormone that decreases the blood glucose concentration. It affects the entire intermediary metabolism, especially of the liver, adipose tissue and muscle. I. increases the permeability of cells to monosaccharides, amino aci and fatty acids, and it accelerates glycolysis, the pentose phosphate cycle, and, in the liver, glycogen synthesis. It promotes the biosynthesis of fatty adds and proteins. These indirect effects on various enzymes and metabolic processes are listed in the tables. 

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. 

Galactose is metabolized slowly by adipose tissue and it thus became important to determine whether the effects of insulin, epinephrine and caffeine on the accumulation of galactose-Cl" were due to an effect on the transport of galactose into the cell or to effect on its subsequent metabolism. If, for example, insulin markedly stimulated the conversion of galactose-other radioactive products without affecting the... 

Recent research into the biology of adipose tissue has revealed that adipose is not simply an energy storage site, but that it also secretes a variety of molecular species that affect the body s metabolism. Adipocytes are cells contained in adipose tissue that have been shown to be endoaine cells that setrete a number of bioactive substances called adipocytokines. The adipocytokines include adiponectin, a protein that is an insulin-sensitizing hormone [59, 60]. The secretion of virtually all known... 

Metabolic Effects of Insulin. Insulin has pronounced effects on the metabolism of carbohydrates, lipids, and proteins. The major tissues affected by insulin are muscle (cardiac and skeletal), adipose ti.ssue, and liver. The kidney is much less responsive, and others (e.g.. hrain tis.sue and red blood cells) do nut respond at all. The actions of insulin arc highly complex and diverse. Because many of the actions of insulin are mediated by. second messengers, it is difficult to distinguish between its primary and secondary actions. 

High blood glucose levels occur because of either a deficiency of insulin (insulin-dependent diabetes mellitus, IDDM) or the inability of tissues such as adipose and muscle to take up glucose in the presence of normal amounts of insulin (insulin resistance or noninsulin-dependent diabetes mellitus [NIDDM]). If insulin-deficiency diabetes mellitus is untreated, the body responds as if it is starving. Fuel stores are degraded in the face of high blood glucose, and ketoacidosis may occur. Many metabolic pathways are affected. 

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