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FMRF-amide is a glucose-lowering hormone in the snail Helix aspersa

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Abstract

Although glucose is metabolically the most important carbohydrate in almost all living organisms, still little is known about the evolution of the hormonal control of cellular glucose uptake. In this study, we identify Phe-Met-Arg-Phe-amide (FMRFa), also known as molluscan cardioexcitatory tetrapeptide, as a glucose-lowering hormone in the snail Helix aspersa. FMRFa belongs to an evolutionarily conserved neuropeptide family and is involved in the neuron-to-muscle signal transmission in the snail digestive system. This study shows that, beyond this function, FMRFa also has glucose-lowering activity. We found neuronal transcription of genes encoding FMRFa and its receptor and moreover the hemolymph FMRFa levels were peaking at metabolically active periods of the snails. In turn, hypometabolism of the dormant periods was associated with abolished FMRFa production. In the absence of FMRFa, the midintestinal gland (“hepatopancreas”) cells were deficient in their glucose uptake, contributing to the development of glucose intolerance. Exogenous FMRFa restored the absorption of hemolymph glucose by the midintestinal gland cells and improved glucose tolerance in dormant snails. We show that FMRFa was released to the hemolymph in response to glucose challenge. FMRFa-containing nerve terminals reach the interstitial sinusoids between the chondroid cells in the artery walls. We propose that, in addition to the known sites of possible FMRFa secretion, these perivascular sinusoids serve as neurohemal organs and allow FMRFa release. This study suggests that in evolution, not only the insulin-like peptides have adopted the ability to increase cellular glucose uptake and can act as hypoglycemic hormones.

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Acknowledgments

This study was performed at the former Department of Animal Anatomy and Physiology, presently a joint department of the Institute of Biology, Debrecen University, Hungary. Figure 1b was provided with courtesy of Dreamstime Stock Photography. Livia I. Lelkes provided editorial assistance; her timely and careful work is appreciated. This article is dedicated to the memory of Dr. Vince Varga, Professor of Animal Physiology at Debrecen University (Hungary) and University of Tampere (Finland).

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  1. Tamás Rőszer

    Present address: Department of General Zoology and Endocrinology, Faculty of Science, University of Ulm, Helmholtz Straße 8/1, 89081, Ulm, Germany

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  1. Department of Animal Anatomy and Physiology, Institute of Biology, Faculty of Science, Debrecen University, Debrecen, Hungary

    Éva D. Kiss-Tóth

  2. Department of Nanobiotechnology and Regenerative Medicine, University of Miskolc, Miskolc, Hungary

    Éva D. Kiss-Tóth

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  1. Tamás Rőszer
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Correspondence to Tamás Rőszer.

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Rőszer, T., Kiss-Tóth, É.D. FMRF-amide is a glucose-lowering hormone in the snail Helix aspersa . Cell Tissue Res 358, 371–383 (2014). https://doi.org/10.1007/s00441-014-1966-x

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