GLUT-4 phosphorylation and its intrinsic activity. Mechanism of Ca(2+)-induced inhibition of insulin-stimulated glucose transport - PubMed (original) (raw)
. 1993 Feb 15;268(5):3352-6.
Affiliations
- PMID: 8381427
Free article
GLUT-4 phosphorylation and its intrinsic activity. Mechanism of Ca(2+)-induced inhibition of insulin-stimulated glucose transport
N Begum et al. J Biol Chem. 1993.
Free article
Abstract
In this study, we examined the influence of high levels of cytosolic calcium on phosphorylation status and function of GLUT-4 in isolated rat adipocytes. Intracellular calcium was elevated by exposing adipocytes to either extracellular ATP (1.6 mM) or thapsigargin (100 nM). Both agents increased cytosolic calcium 2-3 fold. While basal glucose uptake was unaffected, both ATP and thapsigargin reduced insulin-stimulated glucose transport by 40-70% (p < 0.05). Neither ATP nor thapsigargin affected GLUT-4 content or its translocation from the low density microsomes to the plasma membrane (PM). In contrast, GLUT-4 immunoprecipitated from the PM of adipocytes exposed to either ATP or thapsigargin was phosphorylated to a greater extent than the GLUT-4 isolated from control cells. ATP and thapsigargin also abolished insulin-stimulated dephosphorylation of GLUT-4. At the same time, GLUT-4 intrinsic activity was significantly reduced in adipocytes with high levels of cytosolic calcium (p < 0.05). Preincubation of adipocytes with cAMP antagonist, RpcAMP (10(-4) M), and calcium channel blocker, nitrendipine (30 microM), improved the ability of insulin to dephosphorylate GLUT-4 and restored insulin-stimulated GLUT-4 intrinsic activity. We conclude that elevated levels of cytosolic calcium interfere with insulin's ability to dephosphorylate GLUT-4, thus reducing its intrinsic activity.
Similar articles
- Inverse relationship between GLUT-4 phosphorylation and its intrinsic activity.
Reusch JE, Sussman KE, Draznin B. Reusch JE, et al. J Biol Chem. 1993 Feb 15;268(5):3348-51. J Biol Chem. 1993. PMID: 8429011 - Regulation of GLUT-4 phosphorylation by intracellular calcium in adipocytes.
Reusch JE, Begum N, Sussman KE, Draznin B. Reusch JE, et al. Endocrinology. 1991 Dec;129(6):3269-73. doi: 10.1210/endo-129-6-3269. Endocrinology. 1991. PMID: 1659526 - Effect of streptozotocin-induced diabetes on GLUT-4 phosphorylation in rat adipocytes.
Begum N, Draznin B. Begum N, et al. J Clin Invest. 1992 Oct;90(4):1254-62. doi: 10.1172/JCI115988. J Clin Invest. 1992. PMID: 1328294 Free PMC article. - The effects of brefeldin A on the glucose transport system in rat adipocytes. Implications regarding the intracellular locus of insulin-sensitive Glut4.
Bao S, Smith RM, Jarett L, Garvey WT. Bao S, et al. J Biol Chem. 1995 Dec 15;270(50):30199-204. doi: 10.1074/jbc.270.50.30199. J Biol Chem. 1995. PMID: 8530430 - Effects of epinephrine on insulin-stimulated glucose uptake and GLUT-4 phosphorylation in muscle.
Lee AD, Hansen PA, Schluter J, Gulve EA, Gao J, Holloszy JO. Lee AD, et al. Am J Physiol. 1997 Sep;273(3 Pt 1):C1082-7. doi: 10.1152/ajpcell.1997.273.3.C1082. Am J Physiol. 1997. PMID: 9316430
Cited by
- Ca2+/cAMP ratio: An inflammatory index for diabetes, hypertension, and COVID-19.
Bergantin L. Bergantin L. World J Diabetes. 2023 Mar 15;14(3):343-346. doi: 10.4239/wjd.v14.i3.343. World J Diabetes. 2023. PMID: 37035235 Free PMC article. - Chronic Elevation of Skeletal Muscle [Ca2+]i Impairs Glucose Uptake. An in Vivo and in Vitro Study.
Uryash A, Mijares A, Lopez CE, Adams JA, Lopez JR. Uryash A, et al. Front Physiol. 2022 Apr 25;13:872624. doi: 10.3389/fphys.2022.872624. eCollection 2022. Front Physiol. 2022. PMID: 35547584 Free PMC article. - A Review of Coumarins and Coumarin-Related Compounds for Their Potential Antidiabetic Effect.
Ranđelović S, Bipat R. Ranđelović S, et al. Clin Med Insights Endocrinol Diabetes. 2021 Sep 14;14:11795514211042023. doi: 10.1177/11795514211042023. eCollection 2021. Clin Med Insights Endocrinol Diabetes. 2021. PMID: 35173509 Free PMC article. Review. - Association of Serum Calcium and Phosphate Concentrations with Glucose Metabolism Markers: The Furukawa Nutrition and Health Study.
Akter S, Eguchi M, Kochi T, Kabe I, Nanri A, Mizoue T. Akter S, et al. Nutrients. 2020 Aug 5;12(8):2344. doi: 10.3390/nu12082344. Nutrients. 2020. PMID: 32764504 Free PMC article. - Association between Serum Calcium and Risk of Cardiometabolic Disease among Community-dwelling Adults in Taiwan.
Chou CW, Fang WH, Chen YY, Wang CC, Kao TW, Wu CJ, Chen WL. Chou CW, et al. Sci Rep. 2020 Feb 21;10(1):3192. doi: 10.1038/s41598-020-60209-w. Sci Rep. 2020. PMID: 32081877 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous