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

Abstract

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.

Cocaine- and amphetamine-regulated transcript: a novel regulator of energy homeostasis expressed in a subpopulation of pancreatic islet cells

“…In mice, it is also found in a subpopulation of beta cells but it is barely detected in delta cells. In humans, CART (identified as CART 55-102 by western-blot) is consistently expressed in beta-and alpha cells, contrary to what was found in mice and rats [7]. The expression pattern is altered by diabetes and CART expression is strongly upregulated in the beta cells of several animal models of type 2 diabetes, i.e.…”

“…In this issue of Diabetologia, Abels et al [7] explored the possible role of CART in human and mouse islets in healthy conditions and in diabetes. In mice, rats and humans, CART is expressed in islet endocrine cells and in parasympathetic and sensory fibres innervating the islets [20,21,23].…”

“…2). In the normal state, CART is expressed in rats in a subpopulation of delta-and beta cells [7,21,24,25]. In mice, it is also found in a subpopulation of beta cells but it is barely detected in delta cells.…”

“…The expression pattern is altered by diabetes and CART expression is strongly upregulated in the beta cells of several animal models of type 2 diabetes, i.e. in dexamethasone-treated rats, Goto-Kakizaki (GK) rats, Zucker diabetic fatty (ZDF) rats, ob/ob mice, high fat diet fed mice and dominant-negative HNF1α mice [7,21,24]. However, CART remains undetectable in alpha cells of diabetic rodent models [7].…”

“…The GLP-1-based therapeutics improve glucose homeostasis by stimulating insulin secretion, promoting beta cell survival and proliferation, decreasing glucagonaemia, and producing anorexic effects [4][5][6]. In this issue of Diabetologia, the Wierup group (with Abels as first author) shows that cocaine-and amphetamine-regulated transcript (CART) peptides stimulate insulin secretion and inhibit glucagon release from human and mouse islets [7]. Because these peptides also induce weight loss and increase energy expenditure, the authors suggest that CART peptides or their mimetics might be promising agents to combat diabetes.…”