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Expression of Melanin-Concentrating Hormone Receptors in Insulin-Producing Cells: MCH Stimulates Insulin Release in RINm5F and CRI-G1 Cell-Lines

https://doi.org/10.1006/bbrc.2000.3357Get rights and content

Abstract

Melanin-concentrating hormone (MCH) is a hypothalamic orexigenic peptide. Recently, an orphan G-protein-coupled receptor (SLC-1) was identified that binds MCH with high affinity. Here, we demonstrate the mRNA expression of this receptor in insulin-producing cells including CRI-G1 and RINm5F cells, and in rat islets of Langerhans. Immunofluorescence studies in CRI-G1 and RINm5F cell-lines demonstrated cell-surface expression of the receptor. Rat MCH significantly stimulated insulin secretion in both cell-lines. The potency and the efficacy of MCH were significantly increased in the simultaneous presence of forskolin, suggesting that MCH may amplify the insulinotropic effect of cyclic AMP elevating stimuli. Salmon MCH, which differs from rat/human MCH by six amino acids, was less efficacious than rat/human MCH in stimulating insulin release. The data provide evidence for the expression of MCH receptors in insulin producing cells. The insulinotropic effect of MCH may contribute to the regulation of metabolism and energy balance by this peptide.

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    Besides, it is also found in peripheral tissues, such as the β-cells of the pancreas [3], colonic epithelial cells [4] or adipocytes [5,6]. Changes in its expression, both, up and down regulation, are discussed to be involved in a variety of pathologies, such as obesity [7,8], diabetes [3], gut inflammation [4] and depression [9]. Due to its involvement in these lifestyle diseases, MCHR1 has become a very interesting pharmacological target since its discovery in 1999 [10–13].

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