Expression of Cocaine- and Amphetamine-Regulated Transcript Is Associated with Worse Survival in Small Bowel Carcinoid Tumors

Landerholm, Kalle; Shcherbina, Liliya; Falkmer, Sture; Järhult, Johannes; Wierup, Nils

doi:10.1158/1078-0432.ccr-11-2513

Cited by 19 publications

(23 citation statements)

References 30 publications

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“…Specificity of CART antibodies (Cocalico, Reamstown, PA) was verified in CART-/-mice and with pre-absorption with CART55-102 [23]. 30-mer oligodeoxyribonucleotide probes for CART mRNA were used for in situ hybridization (ISH) in human [24] and rat [12] specimens as detailed [25].…”

Section: Immunocytochemistry In Situ Hybridization and Image Analysismentioning

confidence: 99%

CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion

et al. 2016

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CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretionAbels, Mia; Riva, Matteo; Bennet, Hedvig; Ahlqvist, Emma; Dyachok, Oleg; Nagaraj, Vini; Shcherbina, Liliya; Fred, Rikard G.; Poon, Wenny; Sörhede-Winzell, Maria; Fadista, Joao; Lindqvist, Andreas; Kask, Lena; Sathanoori, Ramasri; Dekker-Nitert, Marloes; Kuhar, Michael J.; Ahrén, Bo; Wollheim, Claes B.; Hansson, Ola; Tengholm, Anders; Fex, Malin; Renström, Erik; Groop, Leif; Lyssenko, Valeriya; Wierup, Nils Link to publication Citation for published version (APA): Abels, M., Riva, M., Bennet, H., Ahlqvist, E., Dyachok, O., Nagaraj, V., ... Wierup, N. (2016). CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion. Diabetologia, 59(9), 1928Diabetologia, 59(9), -1937Diabetologia, 59(9), . https://doi.org/10.1007 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. and if CART affects insulin-and glucagon secretion in vitro in humans and in vivo in mice.Methods CART expression was assessed in human type 2 diabetic and non-diabetic control pancreases and diabetic rodent models. Insulin-and glucagon secretion was examined in isolated islets and in vivo in mice. Ca 2+ oscillation patterns and exocytosis was studied in mouse islets.

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Section: Immunocytochemistry In Situ Hybridization and Image Analysismentioning

confidence: 99%

CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion

et al. 2016

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“…Tissues were collected at sacrifice 20 days postoperatively and processed as previously described (12). Antibodies are presented in Table 1.…”

Section: Plasma Analysesmentioning

confidence: 99%

Gastric Bypass Improves β-Cell Function and Increases β-Cell Mass in a Porcine Model

et al. 2014

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The most frequently used and effective treatment for morbid obesity is Roux-en-Y gastric bypass surgery (RYGB), which results in rapid remission of type 2 diabetes in most cases. To what extent this is accounted for by weight loss or other factors remains elusive. To gain insight into these mechanisms, we investigated the effects of RYGB on b-cell function and b-cell mass in the pig, a species highly reminiscent of the human. RYGB was performed using linear staplers during open surgery. Sham-operated pigs were used as controls. Both groups were fed a low-calorie diet for 3 weeks after surgery. Intravenous glucose tolerance tests were performed 2 weeks after surgery. Body weight in RYGB pigs and sham-operated, pair-fed control pigs developed similarly. RYGB pigs displayed improved glycemic control, which was attributed to increases in b-cell mass, islet number, and number of extraislet b-cells. Pancreatic expression of insulin and glucagon was elevated, and cells expressing the glucagon-like peptide 1 receptor were more abundant in RYGB pigs. Our data from a pig model of RYGB emphasize the key role of improved b-cell function and b-cell mass to explain the improved glucose tolerance after RYGB as food intake and body weight remained identical.Roux-en-Y gastric bypass surgery (RYGB) leads to remission of type 2 diabetes (T2D) in most patients within days after surgery (1). Importantly, this occurs long before any substantial weight loss has occurred (2). The reason for this remains a controversy, as studies have shown that the beneficial effects of RYGB on T2D are weight loss independent (e.g., [3]), while others suggest that they result from reduced food intake (4). Clinical studies have shown that RYGB has greater effect on remission of T2D than, for example, vertical sleeve gastrectomy, despite similar weight loss (5). This is in support of weight-independent factors underlying the resolution of T2D upon RYGB. One factor, accounting for the beneficial metabolic effects of RYGB, may be changes in circulating levels of gut hormones and their effects on the islets. In particular, increased levels of the incretin hormone glucagon-like peptide 1 (GLP-1) have been implicated as a factor contributing to remission of T2D (2,6). The effect of RYGB on glucose-dependent insulinotropic peptide (GIP) is less clear (6,7). Other factors, including gut microbiota (8), intestinal glucose sensing (9), and bile acids (10), may also contribute. Nevertheless, it is of great clinical importance to resolve this issue, as it will have a strong impact on how treatment for a large group of patients is devised. In fact, if a specific mechanism were to be identified, it could be used as the basis for a new treatment modality.One problem in the dissection of effects of RYGB on glucose metabolism is that studies on b-cell mass in humans are lacking, and it is extremely difficult to generalize from data in rodents (11) because of huge differences in pancreatic anatomy and physiology between the species. To circumvent these problems, we devel...

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“…Changes in CART expression in the enteric nervous system in pathological states have not been the subject of extensive research and to the best of our knowledge have been investigated only in humans and domestic pigs. It has been demonstrated that inflammatory states affect the number of CART-positive nerve fibres (Gunnarsdottir et al 2007;Gonkowski et al 2009b) and that CART expression is correlated with prognosis in small intestinal carcinoid tumours in humans (Landerholm et al 2012). However, the role of CART in canine IBD has not been studied to date.…”

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confidence: 99%

Cocaine- and amphetamine-regulated transcript immunoreactive nerve fibres in the mucosal layer of the canine gastrointestinal tract under physiological conditions and in inflammatory bowel disease

et al. 2015

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ABSTRACT:The objective of this study was to determine the effect of canine inflammatory bowel disease (IBD) on the density of cocaine-and amphetamine-regulated transcript (CART) immunoreactive nerve fibres in the mucosa of different sections of the gastrointestinal tract. Fibre density was analysed in mucosal specimens from the duodenum, jejunum and descending colon of healthy dogs and patients with inflammatory bowel disease of varying intensity. Nervous fibres were stained in single-cell immunofluorescence assays. The density of CARTimmunoreactive fibres was determined using a semi-quantitative approach by counting the number of fibres in the field of view (0.1 mm 2 ). An increase in the density of CART-immunoreactive fibres was observed in dogs with moderate and severe IBD in comparison with healthy subjects. The results suggest that the presence of CART in enteric nerve fibres could play a role in the pathogenesis and development of canine IBD.

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Expression of Cocaine- and Amphetamine-Regulated Transcript Is Associated with Worse Survival in Small Bowel Carcinoid Tumors

Cited by 19 publications

References 30 publications

CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion

CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion

Gastric Bypass Improves β-Cell Function and Increases β-Cell Mass in a Porcine Model

Cocaine- and amphetamine-regulated transcript immunoreactive nerve fibres in the mucosal layer of the canine gastrointestinal tract under physiological conditions and in inflammatory bowel disease

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