| Autor: |
Nicolai M, Doliba, Marko Z, Vatamaniuk, Carol W, Buettger, Wei, Qin, Heather W, Collins, Suzanne L, Wehrli, Richard D, Carr, Franz M, Matschinsky |
| Rok vydání: |
2003 |
| Předmět: |
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| Zdroj: |
Diabetes. 52(2) |
| ISSN: |
0012-1797 |
| Popis: |
In the present study, noninvasive (31)P and (23)Na(+)-nuclear magnetic resonance (NMR) technology and respirometry were used to compare the effect of high glucose (30 mmol/l) with the effect of the antidiabetic sulfonylurea (SU) compound glyburide (GLY) on energy metabolism, Na(+) flux, insulin, and cAMP release of continuously superfused beta-HC9 cells encapsulated in microscopic agarose beads. Both high glucose and GLY increased oxygen consumption in beta-HC9 cells (15-30%) with a maximal effect at 8 mmol/l for glucose and at 250 nmol/l for GLY. At the same time, insulin release from beta-cells increased by 15- and 25-fold with high glucose or GLY, respectively. The P-creatine (PCr) level was greatly increased and inorganic phosphate (P(i)) was decreased with 30 mmol/l glucose in contrast to the decreased level of PCr and increased P(i) with GLY. ATP levels remained unchanged during both interventions. Studies on isolated mitochondria of beta-HC9 cells showed that GLY added to mitochondria oxidizing glutamine or glutamate abolished the stimulation of respiration by ADP (state 3) meanwhile leaving state 3 respiration unchanged during oxidation of other substrates. Exposure of beta-HC9 cells to 5 mmol/l glucose decreased intracellular Na(+) levels monitored by (23)Na(+)-NMR spectroscopy and 30 mmol/l glucose resulted in a further decrease in cytosolic Na(+). In contrast, Na(+) increased when 1 micro mol/l GLY was added to the perfusate containing 5 mmol/l glucose. These data support the hypothesis that glucose activates the beta-cell through a "push mechanism" due to substrate pressure enhancing fuel flux, energy production, and extrusion of Na(+) from the cells in contrast to SU receptor (SUR)-1 inhibitors, which may modify intermediary and energy metabolism secondarily through a "pull mechanism" due to higher energy demand resulting from increased ion fluxes and the exocytotic work load. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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