CART regulates islet hormone secretion and is expressed in the beta-cells of type 2 diabetic rats.
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 beta-cells during rat development and delta-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 beta-cells of both diabetes models. Thus, in DEX-treated rats, islet CART mRNA expression, and the number of CART-immunoreactive beta-cells were 10-fold higher than in control rats. In GK rats, the relative number of CART-expressing beta-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 beta-cells of type 2 diabetic rats.
Wierup
Nils
N
Department of Experimental Medical Science, Division of Diabetes, Metabolism, and Endocrinology, Lund University, Sweden. nils.wierup@med.lu.se
Björkqvist
Maria
M
Kuhar
Michael J
MJ
Mulder
Hindrik
H
Sundler
Frank
F
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D003907:Dexamethasone; D005947:Glucose; D007328:Insulin; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C428723:cocaine- and amphetamine-regulated transcript protein (55-102); D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein