HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wierup, N. Articles by Sundler, F. Search for Related Content PubMed PubMed Citation Articles by Wierup, N. Articles by Sundler, F. Social Bookmarking                What's this?

CART Regulates Islet Hormone Secretion and Is Expressed in the ß-Cells of Type 2 Diabetic Rats

¹ Department of Experimental Medical Science, Division of Diabetes, Metabolism, and Endocrinology, Lund University, Lund, Sweden
² Yerkes National Primate Research Center of Emory University, Atlanta, Georgia

Address correspondence and reprint requests to Nils Wierup, PhD, Lund University, Department of Experimental Medical Science, Division of Diabetes, Metabolism, and Endocrinology, BMC F10, 22 184, Lund, Sweden. E-mail: nils.wierup{at}med.lu.se

Key Words: CART, cocaine- and amphetamine-regulated transcript • DEX, dexamethasone • GLP-1, glucagon-like peptide-1 • GSIS, glucose-stimulated insulin secretion • HBSS, HEPES-buffered saline solution • IBMX, isobutyl-methylxanthine • PKA, protein kinase A • PP, pancreatic polypeptide • TEM, transmission electron microscope

Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic peptide widely expressed in the central, peripheral, and enteric nervous systems. CART is also expressed in endocrine cells, including ß-cells during rat development and -cells of adult rats. We examined the effect of CART 55–102 on islet hormone secretion, using INS-1(832/13) cells and isolated rat islets. In addition, islet CART expression was examined in two rat models of type 2 diabetes: Goto-Kakizaki (GK) rats and dexamethasone (DEX)-treated rats. At high glucose, CART potentiated cAMP-enhanced insulin secretion via the cAMP/protein kinase A-dependent pathway. In the absence of cAMP-elevating agents, CART was without effect on INS-1 cells but modestly inhibited secretion of insulin, glucagon, and somatostatin from isolated islets. CART was markedly upregulated in the ß-cells of both diabetes models. Thus, in DEX-treated rats, islet CART mRNA expression, and the number of CART-immunoreactive ß-cells were 10-fold higher than in control rats. In GK rats, the relative number of CART-expressing ß-cells was 30-fold higher than in control rats. We conclude that CART is a regulator of islet hormone secretion and that CART is upregulated in the ß-cells of type 2 diabetic rats.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				I. V. Ivanova, R. Schubert, D. B. Duridanova, T. B. Bolton, L. T. Lubomirov, and H. S. Gagov Heart/Cardiac Muscle: Cocaine- and amphetamine-regulated transcript (CART) peptide as an in vivo regulator of cardiac function in Rana ridibunda frog Exp Physiol, November 1, 2007; 92(6): 1037 - 1046. [Abstract] [Full Text] [PDF]

				A. Sen, A. Bettegowda, F. Jimenez-Krassel, J. J. Ireland, and G. W. Smith Cocaine- and Amphetamine-Regulated Transcript Regulation of Follicle-Stimulating Hormone Signal Transduction in Bovine Granulosa Cells Endocrinology, September 1, 2007; 148(9): 4400 - 4410. [Abstract] [Full Text] [PDF]

				A. Vicentic and D. C. Jones The CART (Cocaine- and Amphetamine-Regulated Transcript) System in Appetite and Drug Addiction J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 499 - 506. [Abstract] [Full Text] [PDF]

				R. Arumugam, D. Fleenor, and M. Freemark Lactogenic and Somatogenic Hormones Regulate the Expression of Neuropeptide Y and Cocaine- and Amphetamine-Regulated Transcript in Rat Insulinoma (INS-1) Cells: Interactions with Glucose and Glucocorticoids Endocrinology, January 1, 2007; 148(1): 258 - 267. [Abstract] [Full Text] [PDF]

				B. Ahren, N. Wierup, and F. Sundler Neuropeptides and the Regulation of Islet Function Diabetes, December 1, 2006; 55(Supplement_2): S98 - S107. [Abstract] [Full Text] [PDF]