bucladesine

Summary

Summary: A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)

Top Publications

  1. LaRosa C, Downs S. Stress stimulates AMP-activated protein kinase and meiotic resumption in mouse oocytes. Biol Reprod. 2006;74:585-92 pubmed
    ..Together, these data show that a variety of stresses stimulate GVB in meiotically arrested mouse oocytes in vitro and suggest that this effect is mediated through activation of PRKA. ..
  2. Zahir T, Chen Y, MacDonald J, Leipzig N, Tator C, Shoichet M. Neural stem/progenitor cells differentiate in vitro to neurons by the combined action of dibutyryl cAMP and interferon-gamma. Stem Cells Dev. 2009;18:1423-32 pubmed publisher
    ..These NSPC-derived neurons may be promising for neural regenerative strategies in the CNS. ..
  3. Fouad K, Ghosh M, Vavrek R, Tse A, Pearse D. Dose and chemical modification considerations for continuous cyclic AMP analog delivery to the injured CNS. J Neurotrauma. 2009;26:733-40 pubmed publisher
  4. Tamura K, Yoshie M, Hara T, Isaka K, Kogo H. Involvement of stathmin in proliferation and differentiation of immortalized human endometrial stromal cells. J Reprod Dev. 2007;53:525-33 pubmed
    ..Thus, stathmin expression can be considered an integral factor regulating the initial stage of the process of human endometrial stromal cell differentiation. ..
  5. Azami K, Etminani M, Tabrizian K, Salar F, Belaran M, Hosseini A, et al. The quantitative evaluation of cholinergic markers in spatial memory improvement induced by nicotine-bucladesine combination in rats. Eur J Pharmacol. 2010;636:102-7 pubmed publisher
    We previously showed that post-training intra-hippocampal infusion of nicotine-bucladesine combination enhanced spatial memory retention in the Morris water maze...
  6. Maruoka H, Sasaya H, Shimamura Y, Nakatani Y, Shimoke K, Ikeuchi T. Dibutyryl-cAMP up-regulates nur77 expression via histone modification during neurite outgrowth in PC12 cells. J Biochem. 2010;148:93-101 pubmed publisher
    ..These results suggest that the expression of nur77, which is essential for the neuronal differentiation induced by dbcAMP, is up-regulated via dbcAMP-induced acetylation of the Lys14 of histone H3 in PC12 cells. ..
  7. Pearse D, Pereira F, Marcillo A, Bates M, Berrocal Y, Filbin M, et al. cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nat Med. 2004;10:610-6 pubmed
    ..These findings show that cAMP levels are key for protection, growth and myelination of injured CNS axons in vivo and recovery of function. ..
  8. Gao Y, Nikulina E, Mellado W, Filbin M. Neurotrophins elevate cAMP to reach a threshold required to overcome inhibition by MAG through extracellular signal-regulated kinase-dependent inhibition of phosphodiesterase. J Neurosci. 2003;23:11770-7 pubmed
    ..Together, these results not only show how NGF-like neurotrophins can elevate cAMP and overcome inhibition but also point to a novel mechanism of cross talk in neurons from the Erk to the cAMP signaling pathways. ..
  9. Kao H, Song H, Porton B, Ming G, Hoh J, Abraham M, et al. A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth. Nat Neurosci. 2002;5:431-7 pubmed
    ..These results provide a potential molecular approach for stimulating neuron regeneration, after injury and in neurodegenerative diseases. ..

More Information

Publications62

  1. Jessen U, Novitskaya V, Pedersen N, Serup P, Berezin V, Bock E. The transcription factors CREB and c-Fos play key roles in NCAM-mediated neuritogenesis in PC12-E2 cells. J Neurochem. 2001;79:1149-60 pubmed
    ..We thus present evidence that NCAM-mediated neurite outgrowth involves a series of signal transduction pathways, including the cAMP/PKA pathway, targeting c-Fos and CREB. ..
  2. Qiu J, Cai D, Dai H, McAtee M, Hoffman P, Bregman B, et al. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron. 2002;34:895-903 pubmed
    ..Importantly, DRG injection of db-cAMP results in extensive regeneration of dorsal column axons lesioned 1 week later. These results may be relevant to developing therapies for spinal cord injury. ..
  3. Neumann S, Bradke F, Tessier Lavigne M, Basbaum A. Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron. 2002;34:885-93 pubmed
    ..Thus, stimulating cAMP signaling increases the intrinsic growth capacity of injured sensory axons. This approach may be useful in promoting regeneration after spinal cord injury. ..
  4. Cai D, Deng K, Mellado W, Lee J, Ratan R, Filbin M. Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro. Neuron. 2002;35:711-9 pubmed
    ..Over-expressing Arginase I in maturing DRGs blocks that switch. Arginase I and polyamines are more specific targets than cAMP for intervention to encourage regeneration after CNS injury. ..
  5. Chen X, Piacentino V, Furukawa S, Goldman B, Margulies K, Houser S. L-type Ca2+ channel density and regulation are altered in failing human ventricular myocytes and recover after support with mechanical assist devices. Circ Res. 2002;91:517-24 pubmed
    ..These results suggest that the density of LTCC is reduced in F-HVMs but basal I(Ca,L) density is maintained by increasing in LTCC phosphorylation. ..
  6. Kim G, Choe Y, Park J, Cho S, Kim K. Activation of protein kinase A induces neuronal differentiation of HiB5 hippocampal progenitor cells. Brain Res Mol Brain Res. 2002;109:134-45 pubmed
    ..Taken together, these pharmacological and genetic transfection studies provide compelling evidence for the role of PKA activation on neuronal differentiation in HiB5 hippocampal progenitor cells. ..
  7. van Zeijl C, Fliers E, van Koppen C, Surovtseva O, de Gooyer M, Mourits M, et al. Effects of thyrotropin and thyrotropin-receptor-stimulating Graves' disease immunoglobulin G on cyclic adenosine monophosphate and hyaluronan production in nondifferentiated orbital fibroblasts of Graves' ophthalmopathy patients. Thyroid. 2010;20:535-44 pubmed publisher
  8. Sharifzadeh M, Zamanian A, Gholizadeh S, Tabrizian K, Etminani M, Khalaj S, et al. Post-training intrahippocampal infusion of nicotine-bucladesine combination causes a synergistic enhancement effect on spatial memory retention in rats. Eur J Pharmacol. 2007;562:212-20 pubmed
    ..we wished to test the hypothesis that intrahippocampal infusion of dibutyryl cyclic AMP (DB-cAMP also called bucladesine), a membrane permeable selective activator of PKA, into the CA1 region can cause an improvement in spatial ..
  9. Bui H, Hwang K, Kim J, Van Thuan N, Wakayama T, Miyano T. Effect of vanadate on the chromatin configuration in pig GV-oocytes. J Reprod Dev. 2009;55:367-72 pubmed
    ..These results suggest that inhibition of tyrosine phosphatase(s) in the presence of an effective level of cAMP induces a change in chromatin configuration of pig oocytes. ..
  10. Kanno Y, Ishisaki A, Yoshida M, Nakajima K, Tokuda H, Numata O, et al. Adenylyl cyclase-cAMP system inhibits thyroid hormone-stimulated osteocalcin synthesis in osteoblasts. Mol Cell Endocrinol. 2005;229:75-82 pubmed
    ..These results strongly suggest that the adenylyl cyclase-cAMP system has an inhibitory role in thyroid hormone-stimulated osteocalcin synthesis via suppression of p38 MAP kinase activation in osteoblasts. ..
  11. Imamine H, Mizuno H, Sugiyama Y, Ohro Y, Sugiura T, Togari H. Possible relationship between elevated plasma ACTH and tall stature in familial glucocorticoid deficiency. Tohoku J Exp Med. 2005;205:123-31 pubmed
    ..We speculate that the major causes of excessive growth in FGD are not only from ACTH receptor mutation, but also from the action of elevated plasma ACTH. ..
  12. Bryan B, Cai Y, Wrighton K, Wu G, Feng X, Liu M. Ubiquitination of RhoA by Smurf1 promotes neurite outgrowth. FEBS Lett. 2005;579:1015-9 pubmed
    ..Together, our data suggest that localized regulation of different subsets of Rho GTPases by specific guidance signals results in an intracellular asymmetry of RhoA activity, which could regulate neurite outgrowth and guidance. ..
  13. Hatazawa R, Tanaka A, Tanigami M, Amagase K, Kato S, Ashida Y, et al. Cyclooxygenase-2/prostaglandin E2 accelerates the healing of gastric ulcers via EP4 receptors. Am J Physiol Gastrointest Liver Physiol. 2007;293:G788-97 pubmed
  14. Contestabile A, Fila T, Bartesaghi R, Ciani E. Cyclic AMP-mediated regulation of transcription factor Lot1 expression in cerebellar granule cells. J Biol Chem. 2005;280:33541-51 pubmed
  15. Goto A, Hoshino M, Matsuda M, Nakamura T. Phosphorylation of STEF/Tiam2 by protein kinase A is critical for Rac1 activation and neurite outgrowth in dibutyryl cAMP-treated PC12D cells. Mol Biol Cell. 2011;22:1780-90 pubmed publisher
    ..Considering the critical role of Rac1 in neuronal morphogenesis, the PKA-STEF-Rac1 pathway may play a crucial role in cytoskeletal regulation during neurite/axon outgrowth and guidance, which depend on cAMP signals. ..
  16. Gu R, Wang J, Zhang Y, Li W, Xu Y, Shan H, et al. Adenosine stimulates the basolateral 50 pS K channels in the thick ascending limb of the rat kidney. Am J Physiol Renal Physiol. 2007;293:F299-305 pubmed
    ..We conclude that adenosine activates the 50 pS K channel in the basolateral membrane of the TAL and the stimulatory effect is mainly mediated by a PKA-dependent pathway via the A2 adenosine receptor in the TAL. ..
  17. Oguma T, Kume H, Ito S, Takeda N, Honjo H, Kodama I, et al. Involvement of reduced sensitivity to Ca in beta-adrenergic action on airway smooth muscle. Clin Exp Allergy. 2006;36:183-91 pubmed
    ..Our results may provide evidence that this Ca2+ desensitization is a novel target for a reliever medication using rapid-acting beta-agonists in acute asthma management. ..
  18. Cho H, Kim H, Yu Y, Kang H, Lee D, Rhee M, et al. The opposite correlation between calcium ion and cyclic-AMP regarding the activation of microsomal triglyceride transfer protein in rat liver. BMB Rep. 2009;42:642-7 pubmed
    ..Therefore, our results suggest that high levels of Ca(2+) cause hypertriglyceridemia through the elevation of MTP activity, as opposed to high levels of cAMP, which suppress MTP activity and inhibit hypertriglyceridemia. ..
  19. Bros M, Boissel J, Gödtel Armbrust U, Förstermann U. The untranslated region of exon 2 of the human neuronal nitric oxide synthase (NOS1) gene exerts regulatory activity. Gene. 2007;405:36-46 pubmed
    ..While stimulation of NOS1 expression by dibutyryl-cAMP is mediated by protein kinase A (blocked by H-89), the antiepileptic drug valproic acid is likely to activate phosphatidylinositol-3 kinase (inhibited by LY 294002). ..
  20. Kim J, Havelock J, Carr B, Attia G. The orphan nuclear receptor, liver receptor homolog-1, regulates cholesterol side-chain cleavage cytochrome p450 enzyme in human granulosa cells. J Clin Endocrinol Metab. 2005;90:1678-85 pubmed
    ..We conclude that CYP11A1 expression in human granulosa cells is regulated by LRH-1. We propose that LRH-1 could be the major transcription factor for the post-ovulatory surge in human ovarian steroidogenesis. ..
  21. Kumar A, Tripathi K, Rana M, Purwar S, Garg G. Dibutyryl c-AMP as an inducer of sporidia formation: biochemical and antigenic changes during morphological differentiation of Karnal bunt (Tilletia indica) pathogen in axenic culture. J Biosci. 2004;29:23-31 pubmed
    ..as evidenced from decrease and increase binding of anti-mycelial and anti-sporidial antibodies in dbc-AMP treated culture by ELISA was further interpreted on the basis of morphological differentiation from mycelial to sporidial phase ..
  22. Jacob C, Szilagyi C, Allen J, Bertrand C, Lagente V. Role of PDE4 in superoxide anion generation through p44/42MAPK regulation: a cAMP and a PKA-independent mechanism. Br J Pharmacol. 2004;143:257-68 pubmed
    ..These data suggest that PDE4 inhibitors decreased fMLP-induced O(2)(*-) release in BAL cells enriched in neutrophils but not in macrophages, through p44/42(MAPK) activation by a cAMP- and a PKA-independent mechanism. ..
  23. Weng X, Beyenbach K, Quaroni A. Cultured monolayers of the dog jejunum with the structural and functional properties resembling the normal epithelium. Am J Physiol Gastrointest Liver Physiol. 2005;288:G705-17 pubmed
  24. Baviera A, Zanon N, Navegantes L, Kettelhut I. Involvement of cAMP/Epac/PI3K-dependent pathway in the antiproteolytic effect of epinephrine on rat skeletal muscle. Mol Cell Endocrinol. 2010;315:104-12 pubmed publisher
    ..The parallel activation of PKA-dependent pathway also inhibits proteolysis and seems to limit the stimulatory effect of cAMP on AKT/Foxo3a signaling. ..
  25. Avni D, Philosoph A, Meijler M, Zor T. The ceramide-1-phosphate analogue PCERA-1 modulates tumour necrosis factor-alpha and interleukin-10 production in macrophages via the cAMP-PKA-CREB pathway in a GTP-dependent manner. Immunology. 2010;129:375-85 pubmed publisher
    ..Identification of the PCERA-1 receptor is expected to set up a new target for development of novel anti-inflammatory drugs. ..
  26. Nyachieo A, Spiessens C, Chai D, Kiulia N, Mwenda J, D Hooghe T. Separate and combined effects of caffeine and dbcAMP on olive baboon (Papio anubis) sperm. J Med Primatol. 2010;39:137-42 pubmed publisher
    ..05). Combined and separate effects of caffeine and dbcAMP increases baboon sperm motility and ZP binding ability and may improve baboon IVF. ..
  27. Jasinska A, Strakova Z, Szmidt M, Fazleabas A. Human chorionic gonadotropin and decidualization in vitro inhibits cytochalasin-D-induced apoptosis in cultured endometrial stromal fibroblasts. Endocrinology. 2006;147:4112-21 pubmed
    ..Furthermore, this inhibition of apoptosis may be mediated in part by IGFBP-1 and prolactin and the alteration in the expression of Bcl-2 and Bax. ..
  28. Bergamaschi A, Corsi M, Garnier M. Synergistic effects of cAMP-dependent signalling pathways and IL-1 on IL-6 production by H19-7/IGF-IR neuronal cells. Cell Signal. 2006;18:1679-84 pubmed
    ..These data implicate the role of cAMP-dependent pathways on IL-6 production in neuronal cells and suggest novel synergistic mechanisms of regulation of cytokine production in brain. ..
  29. El Akabawy G, Medina L, Jeffries A, Price J, Modo M. Purmorphamine increases DARPP-32 differentiation in human striatal neural stem cells through the Hedgehog pathway. Stem Cells Dev. 2011;20:1873-87 pubmed publisher
    ..These results demonstrate that small synthetic molecules can play a pivotal role in directing the differentiation of NSCs to optimize their therapeutic potential in HD. ..
  30. Van Elssen C, Vanderlocht J, Oth T, Senden Gijsbers B, Germeraad W, Bos G. Inflammation-restraining effects of prostaglandin E2 on natural killer-dendritic cell (NK-DC) interaction are imprinted during DC maturation. Blood. 2011;118:2473-82 pubmed publisher
    ..The inhibition of NK-DC interaction is a novel regulatory property of PGE2 that is of possible relevance in dampening immune responses in vivo. ..
  31. Yuhki M, Kajitani T, Mizuno T, Aoki Y, Maruyama T. Establishment of an immortalized human endometrial stromal cell line with functional responses to ovarian stimuli. Reprod Biol Endocrinol. 2011;9:104 pubmed publisher
    ..KC02-44D would be useful for studies of human endometrial function and its associated pathologies. ..
  32. Fredsted A, Gissel H, Ortenblad N, Clausen T. Effects of ??-agonists on force during and following anoxia in rat extensor digitorum longus muscle. J Appl Physiol (1985). 2012;112:2057-67 pubmed publisher
    ..These data strongly suggest that this effect is mediated by cAMP stimulation of the Na(+)-K(+) pumps and that it is not related to recovery of energy status (PCr, ATP, lactate)...
  33. Liu D, Liu M, Baker H. Defective protein kinase A and C pathways are common causes of disordered zona pellucida (ZP)--induced acrosome reaction in normozoospermic infertile men with normal sperm-ZP binding. Fertil Steril. 2013;99:86-91 pubmed publisher
    ..Defective upstream of PKC and PKA pathways are highly associated with disordered ZPIAR in normozoospermic infertile men with normal sperm-ZP binding. ..
  34. Manna P, Cohen Tannoudji J, Counis R, Garner C, Huhtaniemi I, Kraemer F, et al. Mechanisms of action of hormone-sensitive lipase in mouse Leydig cells: its role in the regulation of the steroidogenic acute regulatory protein. J Biol Chem. 2013;288:8505-18 pubmed publisher
    ..These findings provide novel insight and demonstrate the molecular events by which HSL acts to drive cAMP/PKA-mediated regulation of StAR expression and steroidogenesis in mouse Leydig cells...
  35. Kume T, Ito R, Taguchi R, Izumi Y, Katsuki H, Niidome T, et al. Serofendic acid promotes stellation induced by cAMP and cGMP analogs in cultured cortical astrocytes. J Pharmacol Sci. 2009;109:110-8 pubmed
  36. Martins Afférri M, Festuccia W, Navegantes L, Garófalo M, Botion L, Kettelhut I, et al. Response to intra- and extracellular lipolytic agents and hormone-sensitive lipase translocation are impaired in adipocytes from rats adapted to a high-protein, carbohydrate-free diet. J Nutr. 2004;134:2919-23 pubmed
  37. Lazarczyk M, Dziunycz P, Niderla J, Milewski L, Lazarczyk M, Boszczyk A, et al. Influence of pentoxifylline on natural cytotoxicity and expression of granzymes and PI-9, a specific granzyme B inhibitor. Int J Mol Med. 2006;17:135-9 pubmed
    ..Altogether, PTX inhibits natural cytotoxicity affecting mainly effector but not target cells and in case of the effector cells, besides previously reported mechanisms, it can also inhibit granzyme A expression. ..
  38. Miyoshi T, Otsuka F, Suzuki J, Takeda M, Inagaki K, Kano Y, et al. Mutual regulation of follicle-stimulating hormone signaling and bone morphogenetic protein system in human granulosa cells. Biol Reprod. 2006;74:1073-82 pubmed
    ..Given that BMPs downregulate FSH receptors in KGN cells, this interaction may contribute to fine-tuning of the mutual sensitivity toward BMP ligands and FSH. ..
  39. Ramis J, Salinas R, García Sanz J, Moreiro J, Proenza A, Lladó I. Depot- and gender-related differences in the lipolytic pathway of adipose tissue from severely obese patients. Cell Physiol Biochem. 2006;17:173-80 pubmed
  40. Kralisch S, Lossner U, Bluher M, Paschke R, Stumvoll M, Fasshauer M. Tissue inhibitor of metalloproteinase 1 expression and secretion are induced by beta-adrenergic stimulation in 3T3-L1 adipocytes. J Endocrinol. 2006;189:665-70 pubmed
    ..Taken together, we demonstrate that TIMP-1 expression and secretion are selectively upregulated in adipocytes by beta-adrenergic agonists via a classic Gs-protein-coupled pathway. ..
  41. Okuma Y, O Connor A, Hayashi T, Loveland K, de Kretser D, Hedger M. Regulated production of activin A and inhibin B throughout the cycle of the seminiferous epithelium in the rat. J Endocrinol. 2006;190:331-40 pubmed
    ..These data provide direct evidence that production of activin A and inhibin B by the Sertoli cell is locally modulated by IL-1alpha , in addition to FSH/cAMP, under the influence of the developing spermatogenic cells...
  42. Pereyra E, Ingerfeld M, Anderson N, Jackson S, Moreno S. Mucor rouxii ultrastructure: cyclic AMP and actin cytoskeleton. Protoplasma. 2006;228:189-99 pubmed
  43. Kim J, Cho Y, Song B, Wee G, Park J, Choo Y, et al. Exogenous dibutyryl cAMP affects meiotic maturation via protein kinase A activation; it stimulates further embryonic development including blastocyst quality in pigs. Theriogenology. 2008;69:290-301 pubmed
  44. Kisslinger A, Cantile M, Sparaneo G, Vitale N, Fabbrocini G, Chieffi P, et al. cAMP and Pyk2 interact to regulate prostate cell proliferation and function. Cancer Biol Ther. 2009;8:236-42 pubmed
    ..These data demonstrated for the first time that Pyk2 and cAMP interact in regulating prostate cell functions and in "keeping" prostate identity. ..
  45. Yamaguchi T, Watanabe Y, Tanaka M, Nakagawa M, Yamaguchi N. cAMP-dependent regulation of spinesin/TMPRSS5 gene expression in astrocytes. J Neurosci Res. 2008;86:610-7 pubmed
    ..These results indicate that m-spinesin is involved in the function of astrocytes in the spinal cord and that there may be astrocyte-specific regulation of its gene expression. ..
  46. Rumajogee P, Vergé D, Darmon M, Brisorgueil M, Hamon M, Miquel M. Rapid up-regulation of the neuronal serotoninergic phenotype by brain-derived neurotrophic factor and cyclic adenosine monophosphate: relations with raphe astrocytes. J Neurosci Res. 2005;81:481-7 pubmed
    ..These data suggest that BDNF and cAMP, but not S100beta, rapidly induce both an up-regulation of the 5-HT neuronal phenotype and modifications of the neighboring astrocytes in a TrkB-dependent manner. ..
  47. Nakajima K, Hirade K, Ishisaki A, Matsuno H, Suga H, Kanno Y, et al. Akt regulates thrombin-induced HSP27 phosphorylation in aortic smooth muscle cells: function at a point downstream from p38 MAP kinase. Life Sci. 2005;77:96-107 pubmed
  48. Lui W, Lee W. cAMP perturbs inter-Sertoli tight junction permeability barrier in vitro via its effect on proteasome-sensitive ubiquitination of occludin. J Cell Physiol. 2005;203:564-72 pubmed
  49. Savina M, Konovalova S, Zubatkina I, Nikiforov A. Reversible metabolic depression in lamprey hepatocytes during prespawning migration: dynamics of mitochondrial membrane potential. Comp Biochem Physiol B Biochem Mol Biol. 2011;160:194-200 pubmed publisher
    ..The potential molecular mechanisms responsible for winter metabolic depression in lamprey hepatocytes are discussed. ..
  50. Nakajima D, Chen F, Yamada T, Sakamoto J, Ohsumi A, Bando T, et al. Reconditioning of lungs donated after circulatory death with normothermic ex vivo lung perfusion. J Heart Lung Transplant. 2012;31:187-93 pubmed publisher
    ..03). Normothermic ex vivo lung perfusion could resuscitate DCD lungs injured by warm ischemia, and may ameliorate ischemia-reperfusion injury. ..
  51. Boer P, Sperling O. Modulation of glycogen phosphorylase activity affects 5-phosphoribosyl-1-pyrophosphate availability in rat hepatocyte cultures. Nucleosides Nucleotides Nucleic Acids. 2004;23:1235-9 pubmed
  52. Hallows K, Alzamora R, Li H, Gong F, Smolak C, Neumann D, et al. AMP-activated protein kinase inhibits alkaline pH- and PKA-induced apical vacuolar H+-ATPase accumulation in epididymal clear cells. Am J Physiol Cell Physiol. 2009;296:C672-81 pubmed publisher
    ..V-ATPase activity may be coupled to the sensing of acid-base status via PKA and to metabolic status via AMPK. ..
  53. Jimenez Feltstrom J, Lundquist I, Salehi A. Glucose stimulates the expression and activities of nitric oxide synthases in incubated rat islets: an effect counteracted by GLP-1 through the cyclic AMP/PKA pathway. Cell Tissue Res. 2005;319:221-30 pubmed
    ..The inhibition of iNOS expression by the GLP-1/cyclic AMP/PKA pathway might possibly be of therapeutic potential in NO-mediated beta-cell dysfunction and destruction. ..