From integrative signalling to metabolic disorders

Otis, Mélissa; Battista, Marie-Claude; Provencher, Mylène; Campbell, Shirley; Roberge, Claude; Payet, M; Gallo‐Payet, Nicole

doi:10.1016/j.jsbmb.2008.03.010

Cited by 6 publications

(2 citation statements)

References 46 publications

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“…DHCR24 was also one of seven genes whose change in expression level after bariatric surgery was positively and highly correlated with changes in the three examined clinical phenotypes: HbA 1C content, weight, and FPG. DHCR24 encodes an enzyme participating in sterol biosynthesis; however, it also binds to p53 and protects it from degradation leading to cellular defense against oxidative stress [32] , [33] . DHCR24 is up regulated in endothelial cells by exposure to HDL, and the HDL mediated lowering of NF-kB and VCAM expression is dependent upon DHCR24 expression [34] .…”

Section: Discussionmentioning

confidence: 99%

Changes in Whole Blood Gene Expression in Obese Subjects with Type 2 Diabetes Following Bariatric Surgery: a Pilot Study

et al. 2011

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BackgroundA pilot study was performed in order to investigate the effects of bariatric surgery on whole blood gene expression profiles in obese subjects with type 2 diabetes.Methodology/Principal FindingsWhole blood from eleven obese subjects with type 2 diabetes was collected in PAXgene tubes prior to and 6–12 months after bariatric surgery. Total RNA was isolated, amplified, labeled and hybridized to Illumina gene expression microarrays. Clinical and expression data were analyzed using a paired t-test, and correlations between changes in clinical trait and transcript levels were calculated. Pathways were identified using Ingenuity Pathway Analysis and DAVID gene ontology software. Overall, bariatric surgery resulted in significant reduction of body mass index, fasting plasma glucose, fasting plasma insulin, and normalization of glycosylated hemoglobin levels. The expression levels of 204 transcripts, representing 200 unique genes, were significantly altered after bariatric surgery. Among the significantly regulated genes were GGT1, CAMP, DEFA1, LCN2, TP53, PDSS1, OLR1, CNTNAP5, DHCR24, HHAT and SARDH, which have been previously implicated in lipid metabolism, obesity and/or type 2 diabetes. Selected findings were replicated by quantitative real-time-PCR. The changes in expression of seven transcripts, WDR35, FLF45244, DHCR24, TIGD7, TOPBP1, TSHZ1, and FAM8A1 were strongly correlated with the changes in body weight, fasting plasma glucose and glycosylated hemoglobin content. The top pathways associated with gene expression changes after bariatric surgery was lipid metabolism, small molecule biochemistry and gene expression. Two antimicrobial peptides were among the transcripts with the largest changes in gene expression after bariatric surgery.Conclusions/SignificanceData from this pilot study suggest that whole blood expression levels of specific transcripts may be useful as biomarkers associated with susceptibility for type 2 diabetes and/or therapeutic response.

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Section: Discussionmentioning

confidence: 99%

Changes in Whole Blood Gene Expression in Obese Subjects with Type 2 Diabetes Following Bariatric Surgery: a Pilot Study

et al. 2011

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“…For the adrenal gland, growth and function can be interpreted by an integrative concept (Otis et al 2008), since the actual number and size of adrenal cells directly impact upon its function (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2

Hoeflich¹,

Bielohuby²

2008

Journal of Molecular Endocrinology

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The adrenal gland influences a multitude of processes during stress response, but also potently affects the immune system, glucose metabolism, electrolyte or water homeostasis, and cardiovascular functions. According to the present understanding, the adrenal cortex is tightly controlled by the hypothalamic-pituitary-adrenal axis. This axis involves hypothalamic CRH and pituitary ACTH which determine processes of adrenocortical growth and function. However, control of the adrenal gland comprises a plethora of additional endogenous or exogenous factors. Among those are diverse hormones, psychosocial parameters, physiological stress, secondary plant products, or even environmental pollutants. In the present review, we summarize the current view of endocrine growth control in the adrenal gland. We then discuss intracellular mechanisms of adrenal growth control and focus on extracellular signal regulated kinases 1/2 ( ERK1/2), which have been demonstrated to be controlled by not only ACTH or angiotensin II, but also by a large number of additional effectors. On the basis of these multiple exogenous or endogenous factors which impact on the adrenal gland through ERK1/2 activity, we speculate on a mechanism by which ERK1/2 act as a central integrative growth regulatory elements in the adrenal gland.

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Steroidogenesis—Adrenal Cell Signal Transduction

Gallo‐Payet

Battista

2014

Comprehensive Physiology

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The purpose of this article is to review fundamentals in adrenal gland histophysiology. Key findings regarding the important signaling pathways involved in the regulation of steroidogenesis and adrenal growth are summarized. We illustrate how adrenal gland morphology and function are deeply interconnected in which novel signaling pathways (Wnt, Sonic hedgehog, Notch, β-catenin) or ionic channels are required for their integrity. Emphasis is given to exploring the mechanisms and challenges underlying the regulation of proliferation, growth, and functionality. Also addressed is the fact that while it is now well-accepted that steroidogenesis results from an enzymatic shuttle between mitochondria and endoplasmic reticulum, key questions still remain on the various aspects related to cellular uptake and delivery of free cholesterol. The significant progress achieved over the past decade regarding the precise molecular mechanisms by which the two main regulators of adrenal cortex, adrenocorticotropin hormone (ACTH) and angiotensin II act on their receptors is reviewed, including structure-activity relationships and their potential applications. Particular attention has been given to crucial second messengers and how various kinases, phosphatases, and cytoskeleton-associated proteins interact to ensure homeostasis and/or meet physiological demands. References to animal studies are also made in an attempt to unravel associated clinical conditions. Many of the aspects addressed in this article still represent a challenge for future studies, their outcome aimed at providing evidence that the adrenal gland, through its steroid hormones, occupies a central position in many situations where homeostasis is disrupted, thus highlighting the relevance of exploring and understanding how this key organ is regulated. © 2014 American Physiological Society. Compr Physiol 4:889-964, 2014.

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From integrative signalling to metabolic disorders

Cited by 6 publications

References 46 publications

Changes in Whole Blood Gene Expression in Obese Subjects with Type 2 Diabetes Following Bariatric Surgery: a Pilot Study

Changes in Whole Blood Gene Expression in Obese Subjects with Type 2 Diabetes Following Bariatric Surgery: a Pilot Study

Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2

Steroidogenesis—Adrenal Cell Signal Transduction

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