Artículos de revistas
Taurine Supplementation Ameliorates Glucose Homeostasis, Prevents Insulin And Glucagon Hypersecretion, And Controls β, α, And δ-cell Masses In Genetic Obese Mice
Registro en:
Amino Acids. Springer-verlag Wien, v. 47, n. 8, p. 1533 - 1548, 2015.
9394451
10.1007/s00726-015-1988-z
2-s2.0-84937725981
Institución
Resumen
Taurine (Tau) regulates β-cell function and glucose homeostasis under normal and diabetic conditions. Here, we assessed the effects of Tau supplementation upon glucose homeostasis and the morphophysiology of endocrine pancreas, in leptin-deficient obese (ob) mice. From weaning until 90-day-old, C57Bl/6 and ob mice received, or not, 5 % Tau in drinking water (C, CT, ob and obT). Obese mice were hyperglycemic, glucose intolerant, insulin resistant, and exhibited higher hepatic glucose output. Tau supplementation did not prevent obesity, but ameliorated glucose homeostasis in obT. Islets from ob mice presented a higher glucose-induced intracellular Ca2+ influx, NAD(P)H production and insulin release. Furthermore, α-cells from ob islets displayed a higher oscillatory Ca2+ profile at low glucose concentrations, in association with glucagon hypersecretion. In Tau-supplemented ob mice, insulin and glucagon secretion was attenuated, while Ca2+ influx tended to be normalized in β-cells and Ca2+ oscillations were increased in α-cells. Tau normalized the inhibitory action of somatostatin (SST) upon insulin release in the obT group. In these islets, expression of the glucagon, GLUT-2 and TRPM5 genes was also restored. Tau also enhanced MafA, Ngn3 and NeuroD mRNA levels in obT islets. Morphometric analysis demonstrated that the hypertrophy of ob islets tends to be normalized by Tau with reductions in islet and β-cell masses, but enhanced δ-cell mass in obT. Our results indicate that Tau improves glucose homeostasis, regulating β-, α-, and δ-cell morphophysiology in ob mice, indicating that Tau may be a potential therapeutic tool for the preservation of endocrine pancreatic function in obesity and diabetes. © 2015 Springer-Verlag. 47 8 1533 1548 Aguila, M.C., McCann, S.M., Stimulation of somatostatin release from median eminence tissue incubated in vitro by taurine and related amino acids (1985) Endocrinology, 116 (3), pp. 1158-1162. , 10.1210/endo-116-3-1158 1:CAS:528:DyaL2MXhsVektr4%3D 2857639 Arany, E., Strutt, B., Romanus, P., Remacle, C., Reusens, B., Hill, D.J., Taurine supplement in early life altered islet morphology, decreased insulitis and delayed the onset of diabetes in non-obese diabetic mice (2004) Diabetologia, 47 (10), pp. 1831-1837. , 10.1007/s00125-004-1535-z 1:CAS:528:DC%2BD2cXpsFKrt7c%3D 15502919 Artner, I., Le Lay, J., Hang, Y., Elghazi, L., Schisler, J.C., Henderson, E., Sosa-Pineda, B., Stein, R., MafB: An activator of the glucagon gene expressed in developing islet alpha- and beta-cells (2006) Diabetes, 55 (2), pp. 297-304. , 1:CAS:528:DC%2BD28XhsFajsr8%3D 16443760 Baek, Y.Y., Cho, D.H., Choe, J., Lee, H., Jeoung, D., Ha, K.S., Won, M.H., Kim, Y.M., Extracellular taurine induces angiogenesis by activating ERK-, Akt-, and FAK-dependent signal pathways (2012) Eur J Pharmacol, 674 (2-3), pp. 188-199. , 10.1016/j.ejphar.2011.11.022 1:CAS:528:DC%2BC38Xks1GqtQ%3D%3D 22130357 Batista, T.M., Ribeiro, R.A., Da Silva, P.M., Camargo, R.L., Lollo, P.C., Boschero, A.C., Carneiro, E.M., Taurine supplementation improves liver glucose control in normal protein and malnourished mice fed a high-fat diet (2013) Mol Nutr Food Res, 57 (3), pp. 423-434. , 10.1002/mnfr.201200345 1:CAS:528:DC%2BC38XhvV2ntLbO 23280999 Bernardis, L.L., Patterson, B.D., Correlation between 'Lee index' and carcass fat content in weanling and adult female rats with hypothalamic lesions (1968) J Endocrinol, 40 (4), pp. 527-528. , 1:STN:280:DyaF1c7ptFWgsg%3D%3D 4868415 Boujendar, S., Reusens, B., Merezak, S., Ahn, M.T., Arany, E., Hill, D., Remacle, C., Taurine supplementation to a low protein diet during foetal and early postnatal life restores a normal proliferation and apoptosis of rat pancreatic islets (2002) Diabetologia, 45 (6), pp. 856-866. , 10.1007/s00125-002-0833-6 1:CAS:528:DC%2BD38XkslSgu7Y%3D 12107730 Bustamante, J., Lobo, M.V., Alonso, F.J., Mukala, N.T., Gine, E., Solis, J.M., Tamarit-Rodriguez, J., Martin Del Rio, R., An osmotic-sensitive taurine pool is localized in rat pancreatic islet cells containing glucagon and somatostatin (2001) Am J Physiol Endocrinol Metab, 281 (6), pp. E1275-E1285. , 1:CAS:528:DC%2BD3MXptlKmt7w%3D 11701444 Cabrera, O., Berman, D.M., Kenyon, N.S., Ricordi, C., Berggren, P.O., Caicedo, A., The unique cytoarchitecture of human pancreatic islets has implications for islet cell function (2006) Proc Natl Acad Sci USA, 103 (7), pp. 2334-2339. , 10.1073/pnas.0510790103 1:CAS:528:DC%2BD28XhslGjtrc%3D 1413730 16461897 Carneiro, E.M., Latorraca, M.Q., Araujo, E., Beltra, M., Oliveras, M.J., Navarro, M., Berna, G., Martin, F., Taurine supplementation modulates glucose homeostasis and islet function (2009) J Nutr Biochem, 20 (7), pp. 503-511. , 10.1016/j.jnutbio.2008.05.008 1:CAS:528:DC%2BD1MXnt1Glsro%3D 18708284 Cerf, M.E., Beta cell dysfunction and insulin resistance (2013) Front Endocrinol, 4, p. 37. , 10.3389/fendo.2013.00037 Chen, N.G., Tassava, T.M., Romsos, D.R., Threshold for glucose-stimulated insulin secretion in pancreatic islets of genetically obese (ob/ob) mice is abnormally low (1993) J Nutr, 123 (9), pp. 1567-1574. , 1:CAS:528:DyaK3sXmtFOqsrs%3D 8360782 Colsoul, B., Jacobs, G., Philippaert, K., Owsianik, G., Segal, A., Nilius, B., Voets, T., Vennekens, R., Insulin downregulates the expression of the Ca2+-activated nonselective cation channel TRPM5 in pancreatic islets from leptin-deficient mouse models (2014) Pflug Arch, 466 (3), pp. 611-621. , 10.1007/s00424-013-1389-7 1:CAS:528:DC%2BC3sXhslGlsLfK Colsoul, B., Schraenen, A., Lemaire, K., Quintens, R., Van Lommel, L., Segal, A., Owsianik, G., Vennekens, R., Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice (2010) Proc Natl Acad Sci USA, 107 (11), pp. 5208-5213. , 10.1073/pnas.0913107107 1:CAS:528:DC%2BC3cXjvFemu70%3D 2841940 20194741 Das, J., Vasan, V., Sil, P.C., Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis (2012) Toxicol Appl Pharmacol, 258 (2), pp. 296-308. , 10.1016/j.taap.2011.11.009 1:CAS:528:DC%2BC38XosFyjsQ%3D%3D 22138235 Gosmain, Y., Katz, L.S., Masson, M.H., Cheyssac, C., Poisson, C., Philippe, J., Pax6 is crucial for beta-cell function, insulin biosynthesis, and glucose-induced insulin secretion (2012) Mol Endocrinol, 26 (4), pp. 696-709. , 10.1210/me.2011-1256 1:CAS:528:DC%2BC38Xlt1ensLg%3D 22403172 Gosmain, Y., Marthinet, E., Cheyssac, C., Guerardel, A., Mamin, A., Katz, L.S., Bouzakri, K., Philippe, J., Pax6 controls the expression of critical genes involved in pancreatic alpha cell differentiation and function (2010) J Biol Chem, 285 (43), pp. 33381-33393. , 10.1074/jbc.M110.147215 1:CAS:528:DC%2BC3cXht12nu7nL 2963382 20592023 Gromada, J., Hoy, M., Buschard, K., Salehi, A., Rorsman, P., Somatostatin inhibits exocytosis in rat pancreatic alpha-cells by G(i2)-dependent activation of calcineurin and depriming of secretory granules (2001) J Physiol, 535, pp. 519-532. , 1:CAS:528:DC%2BD3MXmvFGis7c%3D 2278803 11533141 Gromada, J., Hoy, M., Olsen, H.L., Gotfredsen, C.F., Buschard, K., Rorsman, P., Bokvist, K., Gi2 proteins couple somatostatin receptors to low-conductance K+ channels in rat pancreatic alpha-cells (2001) Pflug Arch, 442 (1), pp. 19-26. , 1:CAS:528:DC%2BD3MXjt1Cht70%3D Gu, C., Stein, G.H., Pan, N., Goebbels, S., Hornberg, H., Nave, K.A., Herrera, P., Lee, J.E., Pancreatic beta cells require NeuroD to achieve and maintain functional maturity (2010) Cell Metab, 11 (4), pp. 298-310. , 10.1016/j.cmet.2010.03.006 1:CAS:528:DC%2BC3cXlsVajur4%3D 2855640 20374962 Hagman, D.K., Hays, L.B., Parazzoli, S.D., Poitout, V., Palmitate inhibits insulin gene expression by altering PDX-1 nuclear localization and reducing MafA expression in isolated rat islets of Langerhans (2005) J Biol Chem, 280 (37), pp. 32413-32418. , 10.1074/jbc.M506000200 1:CAS:528:DC%2BD2MXpvVyqtLs%3D 1361267 15944145 Hart, A.W., Mella, S., Mendrychowski, J., Van Heyningen, V., Kleinjan, D.A., The developmental regulator Pax6 is essential for maintenance of islet cell function in the adult mouse pancreas (2013) PLoS One, 8 (1), p. e54173. , 10.1371/journal.pone.0054173 1:CAS:528:DC%2BC3sXhtlGjs7g%3D 3543312 23326594 Hauge-Evans, A.C., Anderson, R.L., Persaud, S.J., Jones, P.M., Delta cell secretory responses to insulin secretagogues are not mediated indirectly by insulin (2012) Diabetologia, 55 (7), pp. 1995-2004. , 10.1007/s00125-012-2546-9 1:CAS:528:DC%2BC38Xotlelt70%3D 22526610 Hauge-Evans, A.C., King, A.J., Carmignac, D., Richardson, C.C., Robinson, I.C., Low, M.J., Christie, M.R., Jones, P.M., Somatostatin secreted by islet delta-cells fulfills multiple roles as a paracrine regulator of islet function (2009) Diabetes, 58 (2), pp. 403-411. , 10.2337/db08-0792 1:CAS:528:DC%2BD1MXhslersbg%3D 2628614 18984743 Hellman, B., Pulsatility of insulin release - A clinically important phenomenon (2009) Upsala J Med Sci, 114 (4), pp. 193-205. , 10.3109/03009730903366075 2852781 19961265 Hellman, B., Salehi, A., Gylfe, E., Dansk, H., Grapengiesser, E., Glucose generates coincident insulin and somatostatin pulses and antisynchronous glucagon pulses from human pancreatic islets (2009) Endocrinology, 150 (12), pp. 5334-5340. , 10.1210/en.2009-0600 1:CAS:528:DC%2BD1MXhsFGqtbzI 19819962 Huang, H.P., Liu, M., El-Hodiri, H.M., Chu, K., Jamrich, M., Tsai, M.J., Regulation of the pancreatic islet-specific gene BETA2 (neuroD) by neurogenin 3 (2000) Mol Cell Biol, 20 (9), pp. 3292-3307. , 1:CAS:528:DC%2BD3cXivFSrtrs%3D 85623 10757813 Johnson, J.D., Ahmed, N.T., Luciani, D.S., Han, Z., Tran, H., Fujita, J., Misler, S., Polonsky, K.S., Increased islet apoptosis in Pdx1 ± mice (2003) J Clin Investig, 111 (8), pp. 1147-1160. , 10.1172/JCI16537 1:CAS:528:DC%2BD3sXjtFCrsrc%3D 152933 12697734 Johnson, J.H., Ogawa, A., Chen, L., Orci, L., Newgard, C.B., Alam, T., Unger, R.H., Underexpression of beta cell high Km glucose transporters in noninsulin-dependent diabetes (1990) Science, 250 (4980), pp. 546-549. , 1:CAS:528:DyaK3cXmt1yrsL4%3D 2237405 Kahn, S.E., Hull, R.L., Utzschneider, K.M., Mechanisms linking obesity to insulin resistance and type 2 diabetes (2006) Nature, 444 (7121), pp. 840-846. , 10.1038/nature05482 1:CAS:528:DC%2BD28XhtlShtrzP 17167471 Kailey, B., Van De Bunt, M., Cheley, S., Johnson, P.R., MacDonald, P.E., Gloyn, A.L., Rorsman, P., Braun, M., SSTR2 is the functionally dominant somatostatin receptor in human pancreatic beta- and alpha-cells (2012) Am J Physiol Endocrinol Metab, 303 (9), pp. E1107-E1116. , 10.1152/ajpendo.00207.2012 1:CAS:528:DC%2BC38XhvVKmtLbK 3492856 22932785 Kaneto, H., Matsuoka, T.A., Kawashima, S., Yamamoto, K., Kato, K., Miyatsuka, T., Katakami, N., Matsuhisa, M., Role of MafA in pancreatic beta-cells (2009) Adv Drug Deliv Rev, 61 (7-8), pp. 489-496. , 10.1016/j.addr.2008.12.015 1:CAS:528:DC%2BD1MXmsFyhsL4%3D 19393272 Kim, K.S., Da Oh, H., Kim, J.Y., Lee, B.G., You, J.S., Chang, K.J., Chung, H.J., Jeong, I.K., Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes (2012) Exp Mol Med, 44 (11), pp. 665-673. , 10.3858/emm.2012.44.11.075 1:CAS:528:DC%2BC38Xhsl2itL%2FN 3509183 23114424 Lee, E., Ryu, G.R., Ko, S.H., Ahn, Y.B., Yoon, K.H., Ha, H., Song, K.H., Antioxidant treatment may protect pancreatic beta cells through the attenuation of islet fibrosis in an animal model of type 2 diabetes (2011) Biochem Biophys Res Commun, 414 (2), pp. 397-402. , 10.1016/j.bbrc.2011.09.087 1:CAS:528:DC%2BC3MXhtlKrsrfE 21971557 Lindstrom, P., Beta-cell function in obese-hyperglycemic mice [ob/ob Mice] (2010) Adv Exp Med Biol, 654, pp. 463-477. , 10.1007/978-90-481-3271-3-20 20217510 Matsuoka, T.A., Kaneto, H., Miyatsuka, T., Yamamoto, T., Yamamoto, K., Kato, K., Shimomura, I., Matsuhisa, M., Regulation of MafA expression in pancreatic beta-cells in db/db mice with diabetes (2010) Diabetes, 59 (7), pp. 1709-1720. , 10.2337/db08-0693 1:CAS:528:DC%2BC3cXpsVOls7s%3D 2889771 20424231 Maturo, J., Kulakowski, E.C., Taurine binding to the purified insulin receptor (1988) Biochem Pharmacol, 37 (19), pp. 3755-3760. , 1:CAS:528:DyaL1cXmtVGnsbg%3D 3052459 Nadal, A., Quesada, I., Soria, B., Homologous and heterologous asynchronicity between identified alpha-, beta- and delta-cells within intact islets of Langerhans in the mouse (1999) J Physiol, 517, pp. 85-93. , 1:CAS:528:DyaK1MXjvVemu7o%3D 2269319 10226151 Nardelli, T.R., Ribeiro, R.A., Balbo, S.L., Vanzela, E.C., Carneiro, E.M., Boschero, A.C., Bonfleur, M.L., Taurine prevents fat deposition and ameliorates plasma lipid profile in monosodium glutamate-obese rats (2011) Amino Acids, 41 (4), pp. 901-908. , 10.1007/s00726-010-0789-7 1:CAS:528:DC%2BC3MXhtFKitLbK 21042817 Newsholme, P., Haber, E.P., Hirabara, S.M., Rebelato, E.L., Procopio, J., Morgan, D., Oliveira-Emilio, H.C., Curi, R., Diabetes associated cell stress and dysfunction: Role of mitochondrial and non-mitochondrial ROS production and activity (2007) J Physiol, 583, pp. 9-24. , 10.1113/jphysiol.2007.135871 1:CAS:528:DC%2BD2sXhtVSqt7nF 2277225 17584843 Ohneda, M., Johnson, J.H., Inman, L.R., Chen, L., Suzuki, K., Goto, Y., Alam, T., Unger, R.H., GLUT2 expression and function in beta-cells of GK rats with NIDDM. Dissociation between reductions in glucose transport and glucose-stimulated insulin secretion (1993) Diabetes, 42 (7), pp. 1065-1072. , 1:CAS:528:DyaK3sXlsFOnsbc%3D 8513973 Pertusa, J.A., Nesher, R., Kaiser, N., Cerasi, E., Henquin, J.C., Jonas, J.C., Increased glucose sensitivity of stimulus-secretion coupling in islets from Psammomys obesus after diet induction of diabetes (2002) Diabetes, 51 (8), pp. 2552-2560. , 1:CAS:528:DC%2BD38XlvFKhsr0%3D 12145170 Quesada, I., Todorova, M.G., Alonso-Magdalena, P., Beltra, M., Carneiro, E.M., Martin, F., Nadal, A., Soria, B., Glucose induces opposite intracellular Ca2+ concentration oscillatory patterns in identified alpha- and beta-cells within intact human islets of Langerhans (2006) Diabetes, 55 (9), pp. 2463-2469. , 10.2337/db06-0272 1:CAS:528:DC%2BD28XpsVOrt7c%3D 16936194 Quesada, I., Tuduri, E., Ripoll, C., Nadal, A., Physiology of the pancreatic alpha-cell and glucagon secretion: Role in glucose homeostasis and diabetes (2008) J Endocrinol, 199 (1), pp. 5-19. , 10.1677/JOE-08-0290 1:CAS:528:DC%2BD1cXhtleiurrP 18669612 Ribeiro, R.A., Bonfleur, M.L., Amaral, A.G., Vanzela, E.C., Rocco, S.A., Boschero, A.C., Carneiro, E.M., Taurine supplementation enhances nutrient-induced insulin secretion in pancreatic mice islets (2009) Diabetes Metab Res Rev, 25 (4), pp. 370-379. , 10.1002/dmrr.959 1:CAS:528:DC%2BD1MXms1WntLo%3D 19405082 Ribeiro, R.A., Santos-Silva, J.C., Vettorazzi, J.F., Cotrim, B.B., Mobiolli, D.D., Boschero, A.C., Carneiro, E.M., Taurine supplementation prevents morpho-physiological alterations in high-fat diet mice pancreatic beta-cells (2012) Amino Acids, 43 (4), pp. 1791-1801. , 10.1007/s00726-012-1263-5 1:CAS:528:DC%2BC38XhtlOls77N 22418865 Ribeiro, R.A., Vanzela, E.C., Oliveira, C.A., Bonfleur, M.L., Boschero, A.C., Carneiro, E.M., Taurine supplementation: Involvement of cholinergic/phospholipase C and protein kinase a pathways in potentiation of insulin secretion and Ca2+ handling in mouse pancreatic islets (2010) Br J Nutr, 104 (8), pp. 1148-1155. , 10.1017/S0007114510001820 1:CAS:528:DC%2BC3cXht1Oms7fP 20591207 Ripps, H., Shen, W., Review: Taurine: A "very essential" amino acid (2012) Mol Vis, 18, pp. 2673-2686. , 1:CAS:528:DC%2BC38XhvVWms7nI 3501277 23170060 Rukstalis, J.M., Habener, J.F., Neurogenin3: A master regulator of pancreatic islet differentiation and regeneration (2009) Islets, 1 (3), pp. 177-184. , 10.4161/isl.1.3.9877 21099270 Sander, M., Neubuser, A., Kalamaras, J., Ee, H.C., Martin, G.R., German, M.S., Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development (1997) Genes Dev, 11 (13), pp. 1662-1673. , 1:CAS:528:DyaK2sXks1ymt7g%3D 9224716 Scaduto, R.C., Jr., Grotyohann, L.W., Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives (1999) Biophys J, 76 (1), pp. 469-477. , 10.1016/S0006-3495(99)77214-0 1:CAS:528:DyaK1MXjsF2jsw%3D%3D 1302536 9876159 Sharma, A., Olson, L.K., Robertson, R.P., Stein, R., The reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed to high glucose concentration is associated with the loss of RIPE3b1 and STF-1 transcription factor expression (1995) Mol Endocrinol, 9 (9), pp. 1127-1134. , 1:CAS:528:DyaK2MXnvVyktL4%3D 7491105 Strowski, M.Z., Parmar, R.M., Blake, A.D., Schaeffer, J.M., Somatostatin inhibits insulin and glucagon secretion via two receptors subtypes: An in vitro study of pancreatic islets from somatostatin receptor 2 knockout mice (2000) Endocrinology, 141 (1), pp. 111-117. , 1:CAS:528:DC%2BD3cXksleq 10614629 Tomita, T., Doull, V., Pollock, H.G., Krizsan, D., Pancreatic islets of obese hyperglycemic mice (ob/ob) (1992) Pancreas, 7 (3), pp. 367-375. , 1:STN:280:DyaK383nvFWrtQ%3D%3D 1594559 Tsuboyama-Kasaoka, N., Shozawa, C., Sano, K., Kamei, Y., Kasaoka, S., Hosokawa, Y., Ezaki, O., Taurine (2-aminoethanesulfonic acid) deficiency creates a vicious circle promoting obesity (2006) Endocrinology, 147 (7), pp. 3276-3284. , 10.1210/en.2005-1007 1:CAS:528:DC%2BD28XmtlOrsrg%3D 16627576 Uchida, K., Tominaga, M., The role of thermosensitive TRP (transient receptor potential) channels in insulin secretion (2011) Endocr J, 58 (12), pp. 1021-1028. , 1:CAS:528:DC%2BC38XjvValsb8%3D 21785227 Unger, R.H., Orci, L., Paracrinology of islets and the paracrinopathy of diabetes (2010) Proc Natl Acad Sci USA, 107 (37), pp. 16009-16012. , 10.1073/pnas.1006639107 1:CAS:528:DC%2BC3cXhtF2rsr3E 2941311 20798346 Vettorazzi, J.F., Ribeiro, R.A., Santos-Silva, J.C., Borck, P.C., Batista, T.M., Nardelli, T.R., Boschero, A.C., Carneiro, E.M., Taurine supplementation increases K channel protein content, improving Ca handling and insulin secretion in islets from malnourished mice fed on a high-fat diet (2014) Amino Acids, , 24866813 Walker, J.N., Ramracheya, R., Zhang, Q., Johnson, P.R., Braun, M., Rorsman, P., Regulation of glucagon secretion by glucose: Paracrine, intrinsic or both? (2011) Diabetes Obes Metab, 13, pp. 95-105. , 10.1111/j.1463-1326.2011.01450.x 1:CAS:528:DC%2BC3MXhtlaqsrjN 21824262 Wen, J.H., Chen, Y.Y., Song, S.J., Ding, J., Gao, Y., Hu, Q.K., Feng, R.P., Li, L.S., Paired box 6 (PAX6) regulates glucose metabolism via proinsulin processing mediated by prohormone convertase 1/3 (PC1/3) (2009) Diabetologia, 52 (3), pp. 504-513. , 10.1007/s00125-008-1210-x 1:CAS:528:DC%2BD1MXhtlKisLg%3D 19034419 Zhang, C., Moriguchi, T., Kajihara, M., Esaki, R., Harada, A., Shimohata, H., Oishi, H., Takahashi, S., MafA is a key regulator of glucose-stimulated insulin secretion (2005) Mol Cell Biol, 25 (12), pp. 4969-4976. , 10.1128/MCB.25.12.4969-4976.2005 1:CAS:528:DC%2BD2MXlt1Ortb4%3D 1140590 15923615 Zhou, Q., Brown, J., Kanarek, A., Rajagopal, J., Melton, D.A., In vivo reprogramming of adult pancreatic exocrine cells to beta-cells (2008) Nature, 455 (7213), pp. 627-632. , 10.1038/nature07314 1:CAS:528:DC%2BD1cXhtF2hsbvI 18754011