Galanin regulates blood glucose level in the zebrafish: a morphological and functional study

Abstract

The present study has demonstrated the galaninergic innervation of the endocrine pancreas including sources of the galaninergic nerve fibers, and the influence of galanin receptor agonists on blood glucose level in the zebrafish. For the first time, a very abundant galaninergic innervation of the endocrine pancreas during development is shown, from the second day post-fertilization to adulthood. The fibers originated from ganglia consisting of galanin-IR, non-adrenergic (non-sensory) neurons located rostrally to the pancreatic tissue. The ganglia were found on the dorsal side of the initial part of the anterior intestinal segment, close to the intestinal branch of the vagus nerve. The galanin-IR neurons did not show immunoreactivity for applied antibodies against tyrosine hydroxylase, choline acetyltransferase, and vesicular acetylcholine transporter. Intraperitoneal injections of galanin analog NAX 5055 resulted in a statistically significant increase in the blood glucose level. Injections of another galanin receptor agonist, galnon, also caused a rise in blood glucose level; however, it was not statistically significant. The present findings suggest that, like in mammals, in the zebrafish galanin is involved in the regulation of blood glucose level. However, further studies are needed to elucidate the exact mechanism of the galanin action.

A new mode of pancreatic islet innervation revealed by live imaging in zebrafish

“…Both juvenile (25 days post fertilization; dpf) and adult (1 year old) zebrafish display dense innervation networks within the endocrine pancreas ( Figure 1E–F ). By 25 dpf, the celiac ganglion provides sympathetic innervation ( Figure 1E ), as previously described ( Podlasz et al, 2016 ), and at this stage intra-pancreatic innervation between the primary and secondary islets is also present ( Figure 1E ).…”

“…Parasympathetic innervation predominates prior to 5 dpf, but by 25 dpf, sympathetic innervation extending from the celiac ganglia was also detected. Galaninergic nerves have been previously identified in the zebrafish pancreas ( Podlasz et al, 2016 ), and as in non-human primates these nerves are parasympathetic ( Verchere et al, 1996 ). The neurons present on the periphery of the islet as revealed in our studies could give rise to the peri-endocrine nerve plexus which has been observed in rodents ( Tang et al, 2014 ; Ushiki and Watanabe, 1997 ).…”

In vivomonitoring of intracellular Ca2+dynamics in the pancreatic β-cells of zebrafish embryos

“…Consistent with this possibility, it was recently shown that the embryonic zebrafish islet is innervated at the relevant time points, and that a neurotransmitter, namely galanin expressed in these neurons, is involved in blood glucose regulation. 59,60 Notably, the delayed glucose response in the isolated zebrafish islets is similar to that seen in mammalian islets. While this delay is attributed to the time taken for glucose diffusion and metabolism, 61,62 it might be further affected by the cleavage of neural connection during the islet isolation procedure.…”

The novel anticonvulsant neuropeptide and galanin analogue, NAX‐5055, does not alter energy and amino acid metabolism in cultured brain cells

“…Hence, our results imply that NAX‐5055 mediates its anticonvulsant effect without changing cerebral glucose metabolism that may ultimately lead to unwanted side effects. Notably, using NAX‐5055 as a pharmacological tool, GalR1 activation was shown to increase systemic blood glucose levels in mice and zebra fish (Flynn and White, ; Podlasz et al, ). The peripheral hyperglycaemia induced by NAX‐5055 might influence cerebral glucose metabolism in vivo as it has been demonstrated that glucose transporters and particularly GLUT‐1 in the blood‐brain barrier are regulated by ambient glucose concentrations (Vannucci et al, ).…”