Gluconeogenesis glucagon, effect

Insulin inhibits glycogenolysis and gluconeogenesis. Glucagon opposes the effects of insulin and therefore helps to maintain the blood glucose level so that it has the same end result as that of fatty acid oxidation (See Figure 12.14). 

B. Corticosteroids (by decreasing peripheral Insulin resistance and promoting gluconeogenesis), glucagon (by enhanced glycogenolysis), and epinephrine (via beta-adrenergic effects) may antagonize the effects of insulin. 

In adipose tissue, the effect of the decrease in insulin and increase in glucagon results in inhibition of lipo-genesis, inactivation of lipoprotein lipase, and activation of hormone-sensitive lipase (Chapter 25). This leads to release of increased amounts of glycerol (a substrate for gluconeogenesis in the liver) and free fatty acids, which are used by skeletal muscle and liver as their preferred metabolic fuels, so sparing glucose. 

Effects on protein metabolism Glucagon increases uptake of amino acids by the liver, resulting in increased availability of carbon skeletons for gluconeogenesis. As a consequence, plasma levels of amino acids are decreased. 

Figure 17-20 The interlocking pathways of glycolysis, gluconeogenesis, and fatty acid oxidation and synthesis with indications of some aspects of control in hepatic tissues. (— ) Reactions of glycolysis, fatty acid degradation, and oxidation by the citric acid cycle. ) Biosynthetic pathways. Some effects of insulin via indirect action on enzymes , 0, or on transcription 0/ 0. Effects of glucagon , .

Another common mechanism for modulating hormonal response involves two (or more) hormonal inputs with both positive and negative effects (see fig. 24.21). The hypothalamic peptides, somatostatin and GRF, have opposite effects on GH synthesis and secretion. Similarly, glucagon and insulin have opposite effects on gluconeogenesis in the liver (see the discussion earlier in this chapter), and some of the effects of ecdysone on gene expression in insects are blocked by juvenile hormone (a terpene derivative fig. 24.22). 

Protein degradation and amino acid metabolism are highly elevated in the diabetic, because the stimulatory effect of insulin on protein synthesis is nonexistent and the relative excess of glucagon and glucocorticoids causes protein breakdown to continue. Indeed, muscle wasting is a cardinal symptom of the untreated diabetic. Insulin also inhibits amino add release into the bloodstream, and this may be a reason a moderate rise in plasma amino add levels is observed in the diabetic. Such increased amino adds are largely of the branched-chain type, and alanine levels are in fact lower than normal. Nevertheless, alanine uptake by the liver is twice that of the normal individual, and it continues to be a major actor in the gluconeogenesis process. 

Early studies of the stimulatory effects of glucagon on hepatic gluconeogenesis using different gluconeogenic substrates and measuring the changes in the concentrations of intermediary metabolites identified the substrate cycles between pyruvate and P-enolpyruvate and between fructose-1,6-P2 and fructose-6-P as major sites of... 

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