Sökning: id:"swepub:oai:DiVA.org:kth-6059" >
A mathematical mode...
A mathematical model of the mitochondrial NADH shuttles and anaplerosis in the pancreatic beta-cell
-
- Westermark, Pål (författare)
- KTH,Numerisk Analys och Datalogi, NADA,Beräkningsbiologi, CB
-
- Hellgren Kotaleski, Jeanette (författare)
- KTH,Beräkningsbiologi, CB
-
- Björklund, Anneli (författare)
- Karolinska Institutet
-
visa fler...
-
Grill, Valdemar (författare)
-
- Lansner, Anders (författare)
- KTH,Beräkningsbiologi, CB
-
visa färre...
-
(creator_code:org_t)
- American Physiological Society, 2007
- 2007
- Engelska.
-
Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 292:2, s. E373-E393
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
http://kipublication...
-
visa färre...
Abstract
Ämnesord
Stäng
- The pancreatic beta-cells respond to an increased glycolytic flux by secreting insulin. The signal propagation goes via mitochondrial metabolism, which relays the signal to different routes. One route is an increased ATP production that, via ATP-sensitive K+ (K-ATP) channels, modulates the cell membrane potential to allow calcium influx, which triggers insulin secretion. There is also at least one other "amplifying" route whose nature is debated; possible candidates are cytosolic NADPH production or malonyl-CoA production. We have used mathematical modeling to analyze this relay system. The model comprises the mitochondrial NADH shuttles and the mitochondrial metabolism. We found robust signaling toward ATP, malonyl-CoA, and NADPH production. The signal toward NADPH production was particularly strong. Furthermore, the model reproduced the experimental findings that blocking the NADH shuttles attenuates the signaling to ATP production while retaining the rate of glucose oxidation (Eto K, Tsubamoto Y, Terauchi Y, Sugiyama T, Kishimoto T, Takahashi N, Yamauchi N, Kubota N, Murayama S, Aizawa T, Akanuma Y, Aizawa S, Kasai H, Yazaki Y, Kadowaki T. Science 283: 981 - 985, 1999) and provides an explanation for this apparent paradox. The model also predicts that the mitochondrial malate dehydrogenase reaction may proceed backward, toward malate production, if the activity of malic enzyme is sufficiently high. An increased fatty acid oxidation rate was found to attenuate the signaling strengths. This theoretical study has implications for our understanding of both the healthy and the diabetic beta-cell.
Ämnesord
- NATURVETENSKAP -- Data- och informationsvetenskap (hsv//swe)
- NATURAL SCIENCES -- Computer and Information Sciences (hsv//eng)
Nyckelord
- systems biology
- potassium-dependent adenosine triphosphate channel-independent
- pathway of insulin secretion
- reduced nicotinamide adenine dinucleotide
- diabetes
- fatty acid oxidation
- Biology
- Biologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas