2014, Número 2
<< Anterior Siguiente >>
Rev Mex Ing Biomed 2014; 35 (2)
Efecto de Alteraciones en la Producción de ATP y la Sensibilidad a la Glucosa en el Funcionamiento de la Célula β Humana: un Estudio de Simulación
Félix-Martínez GJ, Azpiroz-Leehan J, Ávila-Pozos R, Godínez Fernández JR
Idioma: Ingles.
Referencias bibliográficas: 41
Paginas: 157-170
Archivo PDF: 664.06 Kb.
RESUMEN
En este artículo usamos un modelo matemático para explorar los efectos
de alteraciones en la producción de ATP y sensibilidad a la glucosa en
la respuesta eléctrica y la secreción de insulina en células β humanas.
El modelo fue extendido al añadir ecuaciones empíricas explícitas que
describen recientes observaciones experimentales, como el incremento en
el ATP como función de la concentración de glucosa y las oscilaciones en
el ATP a altos niveles de glucosa. Se realizaron simulaciones a niveles
de glucosa alcanzados durante una prueba de tolerancia a la glucosa
para evaluar la respuesta de la célula β humana en escenarios normales
y patológicos. Nuestras simulaciones reprodujeron varias observaciones
experimentales, tales como la secreción de insulina alterada como
consecuencia de la disfunción de la célula β y la restauración de
la actividad eléctrica al aplicar una sulfonilurea. Nuestros resultados
sugieren que tanto una reducción en la sensibilidad a la glucosa como
la alteración en la producción de ATP podrían estar relacionadas a la
patogénesis de la diabetes tipo 2.
REFERENCIAS (EN ESTE ARTÍCULO)
M.Z. Shrayyef, J.E. Gerich, Normal glucose homeostasis, In: Principles of Diabetes Mellitus, Springer US, 2009: pp. 19-35.
M. Brissova, Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy, J Histochem Cytochem. 53 (2005) 1087-1097.
J.C. Henquin, The dual control of insulin secretion by glucose involves triggering and amplifying pathways in -cells, Diabetes Res Clin Pr. 93 (2011) S27-S31.
D.S. Koh, J.-H. Cho, L. Chen, Paracrine interactions within islets of Langerhans, J Mol Neurosci. 48 (2012) 429-440.
J.V. Rocheleau, et al., Critical role of gap junction coupled KATP channel activity for regulated insulin secretion, PLoS Biol. 4 (2006) e26.
L.E. Fridlyand, et al., Ion channels and regulation of insulin secretion in human -cells: a computational systems analysis, Islets. 5 (2013) 1-15.
A. Basu, et al., Prediabetes: Evaluation of -Cell Function, Diabetes. 61 (2012) 270- 271.
S. Dryselius, et al. Hellman, Variations in ATP-Sensitive K+ channel activity provide evidence for inherent metabolic oscillations in pancreatic -cells, Biochem Biophys Res Commun. 205 (1994) 880-885.
A.H. Rosengren, et al.., Reduced insulin exocytosis in human pancreatic -cells with gene variants linked to type 2 diabetes, Diabetes. 61 (2012) 1726-1733.
P. Rorsman, M. Braun, Regulation of insulin secretion in human pancreatic islets, Annu Rev Physiol 75 (2013) 155-179.
P. Detimary, et al., The changes in adenine nucleotides measured in glucose-stimulated rodent islets occur in cells but not in cells and are also observed in human islets, J Biol Chem. 273 (1998) 33905-33908.
M. Kanat, A. et al., Distinct -cell defects in impaired fasting glucose and impaired glucose tolerance, Diabetes. 61 (2012) 447- 453.
J. Li, H.Y. Shuai, E. Gylfe, A. Tengholm, Oscillations of sub-membrane ATP in glucose-stimulated beta cells depend on negative feedback from Ca2+, Diabetologia. 56 (2013) 1577-1586.
L.E. Fridlyand, N. Tamarina, L.H. Philipson, Bursting and calcium oscillations in pancreatic beta-cells: specific pacemakers for specific mechanisms, Am J Physiol Endocrinol Metab. 299 (2010) E517-32.
M. Hiriart, L. Aguilar-Bryan, Channel regulation of glucose sensing in the pancreatic -cell, Am J Physiol Endocrinol Metab. 295 (2008) E1298-306.
M. Braun, et al., Voltage-gated ion channels in human pancreatic -cells: electrophysiological characterization and role in insulin secretion, Diabetes. 57 (2008) 1618-1628.
M. Riz, et al., Mathematical modeling of heterogeneous electrophysiological responses in human -cells, PLoS Comp Biol. 10 (2014) e1003389.
E. Ferrannini, et al., -Cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis, J Clin Endocrinol Metab. 90 (2005) 493-500.
L.E. Fridlyand, et al., Adenine nucleotide regulation in pancreatic -cells: modeling of ATP/ADP-Ca2+ interactions, Am J Physiol Endocrinol Metab. 289 (2005) E839-48.
S. Nagamatsu, M. Ohara-Imaizumi, Mechanism of insulin exocytosis analyzed by imaging techniques, In: Pancreatic Beta Cell in Health and Disease, Springer Japan, 2008: pp. 177-193.
K. Bokvist, et al., Co-localization of Ltype Ca2+ channels and insulin-containing secretory granules and its significance for the initiation of exocytosis in mouse pancreatic B-cells. EMBO J, 14(1) (1995) 50-57.
E.K. Ainscow, G.A. Rutter, Glucosestimulated oscillations in free cytosolic ATP concentration imaged in single islet -cells: evidence for a Ca2+-dependent mechanism, Diabetes. 51 Suppl 1 (2002) S162-70.
O.P. Ganda, et al., Reproducibility and comparative analysis of repeated intravenous and oral glucose tolerance tests, Diabetes. 27 (1978) 715-725.
J.C. Henquin, et al., Nutrient control of insulin secretion in isolated normal human islets, Diabetes. 55 (2006) 3470-3477.
S.G. Straub, et al., Glucose activates both KATP channel-dependent and KATP channel-independent signaling pathways in human islets, Diabetes. 47 (1998) 758-763.
M. Braun, et al., Exocytotic properties of human pancreatic -cells, Ann NY Acad Sci 1152 (2009) 187-193.
I. Quesada, et al., Glucose induces opposite intracellular Ca2+ concentration oscillatory patterns in identified - and -cells within intact human islets of Langerhans, Diabetes. 55 (2006) 2463- 2469.
L.J. McCulloch, et al, GLUT2 (SLC2A2) is not the principal glucose transporter in human pancreatic beta cells: Implications for understanding genetic association signals at this locus, Mol Genet Metab. 104 (2011) 648-653.
N.M. Doliba, et al., Glucokinase activation repairs defective bioenergetics of islets of Langerhans isolated from type 2 diabetics, Am J Physiol Endocrinol Metab. 302 (2012) E87-E102.
A. Mari, et al., Impaired beta cell glucose sensitivity rather than inadequate compensation for insulin resistance is the dominant defect in glucose intolerance, Diabetologia. 53 (2010) 749-756.
A.I. Tarasov, et al., The mitochondrial Ca2+ uniporter MCU is essential for glucose-induced ATP increases in pancreatic -cells, PloS One. 7 (2012) e39722.
A. Tengholm, E. Gylfe, Oscillatory control of insulin secretion, Mol Cell Endocrinol 297 (2009) 58-72.
P. Bergsten, Pathophysiology of impaired pulsatile insulin release, Diabetes Metab Res Rev. 16 (2000) 179-191.
R. Bertram, et al, Interaction of glycolysis and mitochondrial respiration in metabolic oscillations of pancreatic islets, Biophy J. 92 (2007) 1544-1555.
M.J. Merrins, et al, Phosphofructo- 2-kinase/fructose-2, 6-bisphosphatase modulates oscillations of pancreatic islet metabolism, PloS One. 7 (2012) e34036.
R.T. Kennedy, et al, Metabolic oscillations in -cells, Diabetes 51 Suppl 1 (2002) S152- 61.
D.S. Luciani, Ca2+ controls slow NAD(P)H oscillations in glucose-stimulated mouse pancreatic islets, J Physiol. 572 (2006) 379- 392.
P. Detimary, et al, Interplay between cytoplasmic Ca2+ and the ATP/ADP ratio: a feedback control mechanism in mouse pancreatic islets, Biochem J. 333 (Pt 2) (1998) 269-274.
H. Heimberg, et al, Heterogeneity in glucose sensitivity among pancreatic - cells is correlated to differences in glucose phosphorylation rather than glucose transport, Embo J. 12 (1993) 2873-2879.
S. Klinger, B. Thorens, Molecular Biology of Gluco-Incretin Function, In: Pancreatic Beta Cell in Health and Disease, Springer Japan, 2008: pp. 315-334.
E.R. Pearson, et al., Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations, N Engl J Med. 355 (2006) 467-477.