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

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.

A Multicomponent Neuronal Response Encodes the Larval Decision to Pupariate upon Amino Acid Starvation

“…CCHa2 is expressed predominantly in the fat body ( Sano et al, 2015 ) as well as the brain and the midgut ( Ren et al, 2015 ) of Drosophila larvae and conveys nutritional information about environmental proteins and carbohydrate levels in Drosophila larvae ( Sano et al, 2015 ). The role of FMRFa in nutritional sensing is not understood, although FMRFa regulates glucose metabolism in snails ( Röszer and Kiss-Tóth, 2014 ). AstA regulates feeding of Drosophila larvae depending on the available nutrient content in the environment ( Hentze et al, 2015 ; J. Chen et al, 2016 ) and is known to negatively regulate feeding in adult flies ( Hergarden et al, 2012 ).…”

Changes in the neuropeptide content of Biomphalaria ganglia nervous system following Schistosoma infection

“…The tetrapeptide FMRFa is known to evoke contraction of the smooth muscles in different molluscs [63, 64]. FMRFa has also been shown to increase in the hemolymph of metabolically active Helix aspersa , leading to a decrease in glucose [65]. Thus, the increment of FMRFa-related peptides might suggest that the infected snails may become metabolically more active during this period of parasite infection.…”

Neural Ganglia Transcriptome and Peptidome Associated with Sexual Maturation in Female Pacific Abalone (Haliotis discus hannai)

“…FMRFamide has been identified in diverse animal phyla [11,62,63]. In mollusks, FMRFamide is involved in many physiological regulation processes, including cardioexcitatory activity [63], reproductive activity [64,65], and glucose metabolism [66]. We also detected a higher abundance of the FMRFamide peptide in the PPG of mature female abalone, although the mRNA levels were similar between the immature and mature abalone.…”