Role of membranes and energy-producing reactions in cellular processing of insulin in primary cultures of rat hepatocytes |
| |
| Authors: | M S Morgan R M Darrow M A Nafz P T Varandani |
| |
| Affiliation: | 1. Division of Endocrinology Wright State University, Dayton, Ohio 45435 USA;2. Department of Biological Chemistry Wright State University, Dayton, Ohio 45435 USA;1. Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan;2. Biological and Pharmacological Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka, Japan;1. Department of Physics, Amity University, Kolkata, 700156, West Bengal, India;2. Department of Physics, Jadavpur University, Kolkata, 700032, West Bengal, India;3. Department of Physics, University of Gour Banga, Malda, West Bengal, 732103, India;1. Hacettepe University, Faculty of Pharmacy, Department of Pharmacology, Ankara, Turkey;2. Karadeniz Technical University, Faculty of Pharmacy, Department of Pharmacology, Trabzon, Turkey;3. Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry, Ankara, Turkey;4. Hacettepe University, Faculty of Medicine, Department of Pathology, Ankara, Turkey;5. Hacettepe University, Faculty of Pharmacy, Bioanalytic and Omics Laboratory, Ankara, Turkey |
| |
| Abstract: | Incubation of primary cultures of rat hepatocytes with the local anesthetics, procaine or lidocaine, had little or no effect on insulin uptake or degradation but caused an inhibition of insulin-stimulated glycogenesis. While exposure of cultures to the amines, monodansylcadaverine or CH3NH2, resulted in significant dose-dependent decreases in glycogenesis, only monodansylcadaverine (an inhibitor of receptor clustering) decreased uptake whereas CH3NH2 (a lysosomotropic agent) caused increases in both insulin uptake and degradation. When cells were treated with agents which inhibit glycolysis (NaF, 2-deoxy-D-glucose) or oxidative metabolism (2,4-dinitrophenol, carbonyl cyanide m-chlorophenyl hydrazone, NaN3, antimycin A), pronounced inhibitions of each of the bioactivities studied (syntheses of glycogen, protein, lipid) were observed, but only the glycolytic inhibitors decreased insulin uptake. These results suggest that insulin is internalized by an endocytotic process involving receptor clustering and requiring metabolic energy derived from glycolysis. The post-receptor biosynthetic processes involved in the expression of the biological activities of insulin (syntheses of glycogen, protein, lipid) require energy produced by oxidative metabolism while the degradation of insulin is carried out by nonlysosomal mechanisms which are not energy-requiring. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
