Glucose Homeostasis

Glucose homeostasis is but a part of a more general metabolic homeostasis in which the body regulates and controls the distribution and levels of metabolites in cells. Thus nature ensures that there are always available to enzymes their appropriate substrates the cell cannot afford to 'run out', but conversely degradation offoodstuffs is not to be encouraged unless there is a need for the energy so produced, and this is managed by control of enzymic function. Many enzymes, it has been found in recent years, are subject to complex regulation and control, the full details of which are as yet imperfectly understood and appear to get increasingly involved the more we learn (see Manchester 1967, for a simple outline). If we have glucose homeostasis in the extracellular compartment, we may also say that intracellularly there is a glucose-6-phosphate (G6P) homeostasis. In the liver cell the reactions using and producing G6P are numerous (Fig 1). Although the actual concentration of G6P fluctuates more than does plasma glucose, it is none the less true to say that, given the multiplicity of reactions in which G6P participates, its concentration stays remarkably constant. This is so because many of the reactions or reaction sequences (metabolic pathways) involving it are subject to control. There are for example feedback and feedforward mechanisms G6P activates glycogen synthetase, one of the enzymes involved in glycogen synthesis (Larner et al. 1964). This is a positive feed-forward or forward activation because accumulation of G6P speeds up its own disposal as glycogen. Conversely, in many tissues G6P inhibits hexokinase (Walker 1966). This is a negative feedback, for in this instance accumulation of G6P cuts back the rate of further phosphorylation of glucose. Because of the dynamic nature of metabolism, which presumably allows more flexible control than would a static set-up, we have a continual turnover ofplasma glucose. In the post-absorptive state it might be thought that plasma glucose turnover would be equivalent to total glucose oxidation (which can readily be measured as 14CO2 production from tracer [14C]glucose).