CART Regulates Islet Hormone Secretion and Is Expressed in the {beta}-Cells of Type 2 Diabetic Rats.

Wierup, NilsLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine (author)

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 β-cells during rat development and δ-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 β-cells of both diabetes models. Thus, in DEX-treated rats, islet CART mRNA expression, and the number of CART-immunoreactive β-cells were 10-fold higher than in control rats. In GK rats, the relative number of CART-expressing β-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 β-cells of type 2 diabetic rats.

Björkqvist, MariaLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Biomarkörer vid hjärnsjukdomar,Forskargrupper vid Lunds universitet,Translationell neuroendokrinologi,Department of Experimental Medical Science,Faculty of Medicine,Biomarkers in Brain Disease,Lund University Research Groups,Translational Neuroendocrinology(Swepub:lu)farm-mbj (author)
Kuhar, Michael J (author)
Mulder, HindrikLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)medk-hmu (author)
Sundler, FrankLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)mphy-fsu (author)
Institutionen för experimentell medicinsk vetenskapMedicinska fakulteten (creator_code:org_t)

By the author/editor: Wierup, Nils; Björkqvist, Mari ...; Kuhar, Michael J; Mulder, Hindrik; Sundler, Frank

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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