Metabolic actions of glucagon-family hormones in liver

This review addresses direct and indirect metabolic actions of hormones co-encoded in the preproglucagon gene of fishes. Emphasis is placed on a critical analysis of the effects of glucagon and glucagon-like peptide (GLP) and the current knowledge of the respective modes of action is reviewed. In mammals GLPs exert no direct metabolic actions. In fish liver, GLP and glucagon act on similar targets of intermediary metabolism by enhancing flux through glycogenolysis, lipolysis and gluconeogenesis. Increases in substrate oxidation are not uniform. Hormonal activation of glycogen phosphorylase and triglyceride lipase and inhibition of pyruvate kinase are implicated in these actions. Hormone-dependent hyperglycemia, depletion of hepatic glycogen and increases in free fatty acids are noticeablein vivo. Glucagon also activates hepatic amino acid uptake and ammonia excretion. Glucagon actions are accompanied by large increases in hepatic cAMP and increased phosphorylation of pyruvate kinase. Metabolic effects measured after GLP administration are associated with minor, if any, increases in cAMP and effects on pyruvate kinase are variable. We hypothesize that different hepatic receptors with differing modes of intracellular message transduction are involved in glucagon and GLP actions while targetting identical metabolic routes. Responses of different species of fish cover a wide spectrum, and variation of response with the circannual cycle of experimental animals makes comparisons of results, even within one species, difficult.     

Response of enzyme activities and metabolic intermediate concentrations to epinephrine administration in hepatopancreas and muscle of carp

SUMMARY: Common carp Cyprinus carpio were administered intraperitoneally with 10 μmol epinephrine per 100 g bodyweight, and enzyme activities and metabolic intermediate concentrations were determined in the hepatopancreas and muscle. Glycogen phosphorylase a (GPase a) activity together with cyclic AMP (cAMP) concentration was increased, and glycogen content was decreased in the hepatopancreas and muscle at 2 h after the administration. The epinephrine administration also increased hepatopancreatic glucose-6-phosphatase and fructose-1,6-biphosphatase activities as well as serum glucose, lactate, and free amino acid concentrations. Furthermore, its administration increased phosphofructokinase activity together with lactate, fructose-6-phosphate, adenosine-5'-monophosphate, and adenosine-5'-diphosphate concentrations and decreased citrate concentration in the muscle. Thereafter, almost all parameter concentrations in the hepatopancreas and muscle recovered to the pre-administered levels during 24 h after the administration. These results suggest that epinephrine administration enhanced glycogenolysis and gluconeogenesis in the hepatopancreas, and released glucose into the bloodstream to supply it to the muscle. The blood glucose together with muscle glycogen seems to be metabolized through enhanced glycolysis in the muscle.     

Effects of cortisol on hepatic carbohydrate metabolism and responsiveness to hormones in the sea raven,Hemitripterus americanus

The sea raven, Hemitripterus americanus, is a sit-and-wait, low metabolic rate, marine teleost. The objective of this study was to determine i) whether cortisol implantation (50 mg. kg^-1) for 7 days altered hepatocyte metabolism, and hepatocyte responsiveness to epinephrine, glucagon and insulin, and ii) whether 8 weeks of food-deprivation modified the above response. Cortisol implantation significantly increased hepatocyte total glucose production and oxidation from alanine compared to the sham group. There was no cortisol effect on glycogen breakdown, suggesting that the activation of other pathways, including gluconeogenesis, are required to account for the increased glucose production. Epinephrine-mediated (10^-5M) glycogen breakdown and insulin-mediated (10^-8M) total glucose production were enhanced in hepatocytes of cortisol implanted sea ravens, but there were no change in any glucagon (10^-7M) effects. The enhanced glycogen breakdown in the absence of similar increases in total glucose production with epinephrine indicates mobilization of carbohydrate reserves for endogenous use by the liver. Food-deprivation for 8 weeks significantly decreased condition factor, plasma cortisol concentration and liver glycogen content in the sea raven, but had no effect on plasma glucose concentration. Hepatocyte total glucose production and flux rates from alanine increased significantly with food-deprivation. Moreover, food-deprivation increased responsiveness of total hepatocyte glucose production to the actions of glucagon and insulin, but not to epinephrine; none of these effects were modified by cortisol implantation. Our results indicate that cortisol in the sea raven exerts both a direct and an indirect or permissive effect on hepatocyte metabolism by modifying hepatocyte responsiveness to epinephrine and insulin stimulation. Cortisol implantation did not modify the effects of glucagon or food-deprivation in this species.     

蓝点马鲛鱼皮抗氧化肽段对熟肉糜脂肪和蛋白氧化抑制作用的研究

为研究蓝点马鲛鱼皮多肽在肉体系中的抗氧化作用,以猪肉糜为材料,探讨了蓝点马鲛鱼皮抗氧化肽段对冷藏过程中熟肉糜脂肪和蛋白氧化的抑制效果。将实验肉糜分为6组,第1组为空白对照组,第2组加入2.0%的6 h蓝点马鲛鱼皮冻干水解物,第3~5组中分别加入1.0%、1.5%和2.0%的超滤肽段FractionⅡ(分子量1~4 ku;羟基清除率达55.1%)冻干粉,第6组中加0.02%的BHA。在4℃冷藏过程中测定熟肉糜的硫代巴比妥酸值(TBARS)、过氧化值(PV)、羰基含量、总巯基含量和pH值,并对感官指标进行了评定。结果表明,与空白对照比,添加蓝点马鲛鱼皮6 h水解物和抗氧化肽段(FractionⅡ)的熟肉糜处理组能够通过降低肉糜的TBARS值和PV值及降低羰基含量和减少巯基的损失,在一定程度上抑制脂肪和蛋白氧化的发生,其中超滤后的FractionⅡ效果要比6 h水解物好。同时,添加FractionⅡ能够保持熟肉糜鲜红的色泽,抑制变味、酸败味的发生、提高了整体感官评价值,且在一定范围内,添加量越大效果越好。在整个贮藏过程中,分子量在1~4 ku的蓝点马鲛鱼皮抗氧化肽段FractionⅡ处理组表现出更好的抑制熟肉糜氧化效果;其中2.0%处理组在冷藏第8天的TBARS值、PV值、羰基含量、总巯基含量和pH值分别为1.39 mg/kg、1.57 meq/kg、8.27 nmol/kg、49.6 nmol/kg蛋白和6.35,有效保持了熟肉糜的品质。可见,蓝点马鲛鱼皮多肽添加到肉糜中能够有效抑制脂肪和蛋白氧化的发生,是潜在的食源性抗氧化剂。