Fatty acid and amino acid modulation of glucose cycling in isolated rat hepatocytes
| Autor: | Gustafson, LA, Neeft, M, Reijngoud, DJ, Kuipers, F, Sauerwein, HP, Romijn, JA, Herling, AW, Burger, HJ, Meijer, AJ |
|---|---|
| Přispěvatelé: | Other departments, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Reproductive Origins of Adult Health and Disease (ROAHD), Center for Liver, Digestive and Metabolic Diseases (CLDM), Life Course Epidemiology (LCE) |
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: | |
| Zdroj: | Biochemical journal, 358(Part 3), 665-671. Portland Press Ltd. Biochemical Journal, 358, 665-671. PORTLAND PRESS LTD |
| ISSN: | 0264-6021 |
| Popis: | We studied the influence of glucose/glucose 6-phosphate cycling on glycogen deposition from glucose in fasted-rat hepatocytes using S4048 and CP320626, specific inhibitors of glucose-6-phosphate translocase and glycogen phosphorylase respectively. The effect of amino acids and oleate was also examined. The following observations were made: (1) with glucose alone, net glycogen production was low. Inhibition of glucose-6-phosphate translocase increased intracellular glucose 6-phosphate (3-fold), glycogen accumulation (5-fold) without change in active (dephosphorylated) glycogen synthase (GSa) activity, and lactate production (4-fold). With both glucose 6-phosphate translocase and glycogen phosphorylase inhibited, glycogen deposition increased 8-fold and approached reported in vivo rates of glycogen deposition during the fasted → fed transition. Addition of a physiological mixture of amino acids in the presence of glucose increased glycogen accumulation (4-fold) through activation of GS and inhibition of glucose-6-phosphatase flux. Addition of oleate with glucose present decreased glycolytic flux and increased the flux through glucose 6-phosphatase with no change in glycogen deposition. With glucose 6-phosphate translocase inhibited by S4048, oleate increased intracellular glucose 6-phosphate (3-fold) and net glycogen production (1.5-fold), without a major change in GSa activity. It is concluded that glucose cycling in hepatocytes prevents the net accumulation of glycogen from glucose. Amino acids activate GS and inhibit flux through glucose-6-phosphatase, while oleate inhibits glycolysis and stimulates glucose-6-phosphatase flux. Variation in glucose 6-phosphate does not always result in activity changes of GSa. Activation of glucose 6-phosphatase flux by fatty acids may contribute to the increased hepatic glucose production as seen in Type 2 diabetes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|