FIGURE 1.

Glucagon ensures energy supply by mobilizing lipids. In the fasting state, glucagon is secreted and insulin concentrations are not sufficient to inhibit lipolysis in adipocytes, where lipids are stored in lipid droplets consisting of a core of triglycerols (TG) and sterols esters coated with perilipins (P) (proteins restricting access to the lipid core). In response to an appropriate stimuli, e.g., epinephrine and possibly glucagon, AC found in the plasma membrane of the adipocyte is activated, leading to increased intracellular concentrations of cAMP stimulating protein kinase A (PKA) activity. PKA phosphorylates (hence activates) hormone sensitive lipase (HSL) and P. The phosphorylation of P results in dissociation of the protein CGI-58. CGI-58 activates adipose triglycerol lipase (ATGL), which converts TGs to diaglycerols (DG). The phosphorylated P bind HSL and allows it to access the lipid droplet where it coverts DGs to monoglycerols (MG). The monoglycerols are hydrolyzed by monoacylglycerol lipase (MGL), yielding free fatty acids (FFAs) and glycerol, which are released to the blood. FFAs may stimulate glucagon secretion, and glucagon in turn stimulates hepatic gluconeogenesis (using FFAs and glycerol as substrates), glycogenolysis, and beta-oxidation thus providing substrates for the liver to secure sufficient energy supply to metabolically active tissue. Enzymes are written in italic and arrows indicate stimulation.