Expression of melanin-concentrating hormone receptors in insulin-producing cells: MCH stimulates insulin release in RINm5F and CRI-G1 cell-lines.
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.
Tadayyon
M
M
Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Harlow, CM19 5AD, United Kingdom. M_Tadayyon@sbphrd.com
Welters
H J
HJ
Haynes
A C
AC
Cluderay
J E
JE
Hervieu
G
G
D000818:Animals; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006801:Humans; D007028:Hypothalamic Hormones / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007340:Insulinoma / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008543:Melanins / Q000494:pharmacology*; D010907:Pituitary Hormones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011979:Receptors, Pituitary Hormone / Q000235:genetics* / Q000378:metabolism
D007028:Hypothalamic Hormones; D007328:Insulin; D008543:Melanins; D010907:Pituitary Hormones; D012333:RNA, Messenger; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor; C019463:melanin-concentrating hormone