Extrahepatic Regulation

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A key factor in the regulation of ketogenesis is the availability of nonesterified long-chain fatty acids to the liver, which in turn is controlled by their release from adipose tissue. The enzyme responsible for the initiation of the hydrolysis of stored triacylglycerols to fatty acids is hormone-sensitive lipase. As its name implies, this enzyme is exquisitely sensitive to hormones: adrenaline (in the plasma) and noradrenaline (released from sympathetic nerve endings) are activators, whereas insulin inhibits the activity. In small mammals glucagon is also an activator of the enzyme, but this does not seem to be the case in the human.

Insulin has an additional effect on the net release of long-chain fatty acids from adipose tissue in that it stimulates their reesterification to triacylglycerols. Thus after a high-carbohydrate meal, when insulin secretion and its concentration in the plasma is high, the release of fatty acids from adipose tissue is suppressed and their concentration in the plasma is low (Figure 2). In contrast, during stress, when adrenaline and noradrenaline are elevated, the release of fatty acids is increased and their plasma concentration is high.

In experimental animals increased plasma ketone body concentrations (hyperketonemia) can inhibit adipose tissue lipolysis (a) indirectly by increasing the secretion of insulin or (b) by a direct effect on the tissue (Figure 3). This can be viewed as a feedback mechanism for controlling the rate of ketogen-esis via fatty acid supply to the liver, but whether

Figure 2 Intertissue fluxes of substrates in the fed state. Thickness of line denotes rate of flux.

this is important in the human is not known. In contrast, the supply of short- and medium-chain fatty acids to the liver is mainly dependent on the dietary intake and on the proportion that escapes further metabolism in the intestinal tract; there is no known involvement of hormones in the process.

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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