title: Modulation by insulin and glucagon of noradrenaline-induced activation of isolated brown adipocytes from the rat.
abstract: 1. The effects of insulin (2 nM and 4 nM) upon oxygen consumption (VO2), lipolysis rates and indirectly derived rates of fatty acid utilization, by isolated brown adipocytes from warm-acclimated (W cells) and cold-acclimated (C cells) animals, induced by noradrenaline and glucagon separately and conjointly, are reported. 2. Changes in interrelationships (coupling) between the parameters under different treatment regimes were assessed using bivariate regression analyses. 3. Administration of glucagon with noradrenaline increased lipolysis/fatty acid utilization coupling without concomitant increase of VO2 suggesting that glucagon may increase re-esterification through glycogenolytic generation of glycerol 3-phosphate, trapping intracellular fatty acid in excess of the capacity of disposal mechanisms, thus conserving respiratory substrate. 4. W cells were unresponsive to glucagon in terms of lipolysis and VO2, C cells responded to glucagon with parallel increases in lipolysis rate and VO2. Both cell types responded to noradrenaline alone and conjointly with glucagon; C cells were more sensitive to these agonists than W cells. 5. Lipolysis/VO2 coupling was reduced in C cells suggesting that in cold acclimation, noradrenaline-induced lipolysis rates are in excess of the capacity of cellular oxidation/re-esterification mechanisms. 6. Insulin inhibited noradrenaline and glucagon-induced lipolysis, simultaneously increasing VO2, supporting the hypothesis that glucose may be a thermogenic substrate in brown adipase tissue, permitting concurrent thermogenesis and lipogenesis. C cells were more insulin-sensitive than W cells. 7. The data indicate that insulin may mediate its effects (additively with noradrenaline) by activation of pyruvate dehydrogenase, generating glycolytic flux and, in the presence of noradrenaline-inhibited lipogenesis, generate additional oxaloacetate, permitting increased beta-oxidation.
authors.affiliation: Department of Biochemistry, University of Surrey, Guildford, England.
authors.forename: R J
authors.initials: RJ
authors.lastname: Howland
authors.forename: K D
authors.initials: KD
authors.lastname: Bond
mesh_terms: D000064:Acclimatization; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis; D013696:Temperature
chemical_list: D005227:Fatty Acids; D007328:Insulin; D005934:Glucagon; D009638:Norepinephrine