In the absence of insulin, peripheral glucose utilization decreases, leading to a decrease in the amount of glucose used by non-essential tissues. This allows more glucose to be conserved for vital tissues such as the brain. This change in glucose utilization is indicated by Fig. 41.21 (bottom).

GH secretion is beneficial because it causes a shift in metabolism, making lipid the main source of energy. This conserves carbohydrate and protein. The liver, muscle, and adipose tissue are all directly affected by GH, as shown in Fig. 41.20 (red arrowheads).

GH acts as a lipolytic hormone, mobilizing fatty acids and glycerol from triacylglycerol in adipocytes. It achieves this through both direct and indirect activation of adipocyte lipases. An indirect effect of GH is the sensitization of adipocytes to the lipolytic actions of catecholamines, which are also elevated during fasting. As a result of GH action, serum fatty acid levels increase and more fats are used for energy production. Skeletal muscle and liver increase their uptake and oxidation of fatty acids. In the absence of insulin, GH promotes the oxidation of fatty acids, which can result in the production of ketone bodies. GH also affects carbohydrate metabolism, causing an increase in blood glucose levels. Some of its actions may be due to increased fat mobilization and oxidation. For example, an increase in serum free fatty acids inhibits the uptake of glucose in skeletal muscle and adipose tissue. Although the hyperglycemic effects of GH are mild and slower compared to those of glucagon and epinephrine, it does increase liver glucose output. However, this is not due to the effect of GH on glycogenolysis. The increase in fatty acid oxidation and the resulting rise in liver acetyl CoA stimulate gluconeogenesis. GH also directly stimulates the expression of the gluconeogenic enzyme PEPCK through activation of STAT5b. These actions lead to an increase in glucose production by the liver from substrates such as lactate and glycerol. GH-induced lipolysis in adipocytes causes the release of glycerol into the circulation, contributing to gluconeogenesis.
Fig. 41.21, bottom). In the absence of insulin, peripheral glucose utilization decreases, thereby conserving glucose for essential tissues such as the brain. In these circumstances the rise in 750 SECTION8Berne & Levy Physiology •Fig. 41.20 BiologicaleffectsofGHandIGF-I.Anabolicgrowth-promotingeffectsthatoccurwhennutritionalstatusisfavorableareindicatedbygreenarrowheads.MetaboliceffectsofGHthatmobilizefatwhilesparingglucoseandproteinduringfastingaredenotedbyredarrowheads.IGFBP,insulinlikegrowthfactor–bindingprotein.Adipose tissue GH Liver Muscle ˜ Lean body mass ˛ Adiposity ˛ Glucose uptake ˜ Lipolysis ˜ RNA synthesis ˜ Protein synthesis ˜ Gluconeogenesis ˜ IGFBP ˜ IGFs ˛ Glucose uptake ˜ Amino acid uptake ˜ Protein synthesis IGF-I fed state fasted state Kidney Pancreas Intestine Islets Parathyroids Skin Connective tissue Bone, heart, lung ˜ Protein synthesis ˜ RNA synthesis ˜ DNA synthesis ˜ Cell size and number ˜ Amino acid uptake ˜ Protein synthesis ˜ RNA synthesis ˜ DNA synthesis ˜ Collagen ˜ Chondroitin sulfate ˜ Cell size and number ˜ Linear growth Chondrocytes ˜ Organ size ˜ Organ function ˜ Caloric mobilization (e.g., lipids) •Fig. 41.21 DifferentialregulationofGH,insulin,andIGF-Isecretioncoordinatesavailabilityofnutrientswithgrowthandproteinanabolism,caloricstorage,orcaloricmobilization(primarilylipids).
GH secretion is beneficial because it shifts metabolism to lipid as an energy source, thereby conserving carbohydrate and protein. This involves coordinated direct actions of GH on the liver, muscle, and adipose tissue (see
Fig. 41.20 , red arrowheads).
GH is a lipolytic hormone. In adipocytes it mobilizes fatty acids and glycerol from triacylglycerol by combined direct and indirect activation of adipocyte lipases. An important indirect action of GH is sensitization of adipocytes to the lipolytic actions of catecholamines, which are also elevated during fasting. Serum fatty acid levels rise as a result of GH action, and more fats are used for energy production. Fatty acid uptake and β-oxidation increase in skeletal muscle and liver. GH can be ketogenic as a result of the increase in fatty acid oxidation when insulin is absent. GH also alters carbohydrate metabolism, causing blood glucose levels to rise. Many of its actions may be secondary to increased fat mobilization and oxidation. For example, an increase in serum free fatty acids inhibits uptake of glucose in skeletal muscle and adipose tissue. The hyperglycemic effects of GH are mild and slower than those of glucagon and epinephrine. Liver glucose output increases, but this is not an effect of GH on glycogenolysis. The increase in fatty acid oxidation and hence the rise in liver acetyl CoA stimulate gluconeogenesis. GH also directly stimulates expression of the gluconeogenic enzyme PEPCK through activation of STAT5b. These actions increase glucose production by the liver from substrates such as lactate and glycerol. The latter is released into the circulation as a result of GH-induced lipolysis in adipocytes.