Activating transcription factor-2 is a positive regulator in CaM kinase IV-induced human insulin gene expression.

Ban, Nobuhiro; Yamada, Yoshio; Someya, Yoshimichi; Ihara, Yu; Adachi, Tomohiko; Kubota, Akira; Watanabe, Rie; Kuroe, Akira; Inada, Akira; Miyawaki, Kazumasa; Sunaga, Yasuhiro; Shen, Zhenping; Iwakura, Toshio; Tsukiyama, Katsushi; Toyokuni, Shinya; Tsuda, Kinsuke; Seino, Yutaka

doi:10.2337/diabetes.49.7.1142

Cited by 71 publications

(60 citation statements)

References 25 publications

(28 reference statements)

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“…As O-GlcNAc has been implicated in nutrient sensing and the development of insulin-resistant diabetes (3,4), it is interesting that ATF-2 appears to play multiple roles in glucose homeostasis. For instance, ATF-2 has been shown to up-regulate transcription from the insulin promoter in human pancreatic ␤ cells in a Ca 2ϩ ͞calmodulin-dependent protein kinase IV-dependent manner (37). Moreover, recent studies indicate that ATF-2 activates the gluconeogenic gene phosphoenolpyruvate carboxykinase in HepG2 hepatic cells upon retinoic acid induction (38).…”

Section: Discussionmentioning

confidence: 99%

Exploring the O -GlcNAc proteome: Direct identification of O -GlcNAc-modified proteins from the brain

Khidekel

Ficarro²,

Peters³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

280

250

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Section: Discussionmentioning

confidence: 99%

Exploring the O -GlcNAc proteome: Direct identification of O -GlcNAc-modified proteins from the brain

Khidekel

Ficarro²,

Peters³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

280

250

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“…However, co-transfection with a dominant negative form of a related bZIP protein activating transcription factor 2 (ATF-2) did not have an effect on RIP1. This is interesting as ATF-2 was previously demonstrated to mediate human insulin gene transcription via CRE (Ban et al, 2000). Thus a comparison of the studies on the occupancy of the regulatory elements on rat and human insulin promoters in response to GLP-1 treatment should serve a caution to transferring knowledge between the two species.…”

Section: Glp-1 Regulation Of Insulin Transcriptionmentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

576

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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“…Although CREB-mediated gene expression has been characterised in neurons, limited information is available regarding its role in beta cell survival [26][27][28]. The promoter region of the c-IAP2 gene, which belongs to the family of inhibitors of apoptosis, contains CRE sites [29].…”

Section: Discussionmentioning

confidence: 99%

Dominant negative mutant forms of the cAMP response element binding protein induce apoptosis and decrease the anti-apoptotic action of growth factors in human islets

Sarkar¹,

Gunter

Bouchard

et al. 2007

Diabetologia

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Aims/hypothesis Transplantation of islets is a viable option for the treatment of diabetes. A significant proportion of islets is lost during isolation, storage and after transplantation as a result of apoptosis. cAMP response element binding protein (CREB) is an important cell survival factor. The aim of the present study was to determine whether preservation of CREB function is needed for survival of human islets. Materials and methods To determine the effects of downregulation of CREB activity on beta cell apoptosis in a transplantation setting, adenoviral vectors were used to express two dominant negative mutant forms of CREB in human islets isolated from cadaveric donors. Markers of apoptosis were determined in these transduced islets under basal conditions and following treatment with growth factor. Results Expression of CREB mutants in human islets resulted in significant (p<0.001) activation of caspase-9, a key regulatory enzyme in the mitochondrial pathway of apoptosis, when compared with islets transduced with adenoviral beta galactosidase. Immunocytochemical analysis showed the activation of caspase-9 to be predominantly in beta cells. Other definitive markers of apoptosis such as parallel activation of caspase-3, accumulation of cleaved poly-(ADP-ribose) polymerase and nuclear condensation were also observed. Furthermore, the anti-apoptotic action of growth factors exendin-4 and betacellulin in human islets exposed to cytokines was partially lost when CREB function was impaired. Conclusions/interpretation Our findings suggest that impairment of CREB-mediated transcription could lead to loss of islets by apoptosis with potential implications in islet transplantation as well as in the mechanism of beta cell loss leading to diabetes.

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Activating transcription factor-2 is a positive regulator in CaM kinase IV-induced human insulin gene expression.

Cited by 71 publications

References 25 publications

Exploring the O -GlcNAc proteome: Direct identification of O -GlcNAc-modified proteins from the brain

Exploring the O -GlcNAc proteome: Direct identification of O -GlcNAc-modified proteins from the brain

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Dominant negative mutant forms of the cAMP response element binding protein induce apoptosis and decrease the anti-apoptotic action of growth factors in human islets

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