UNC 0631 A single ICV injection of GALP
A single ICV injection of GALP stimulated food intake in goldfish at 1h post-administration. This result is similar to that observed in rats, where ICV injection of GALP exerted an acute orexigenic effect , , . Simultaneously, our findings counter the results found in mice, where centrally administered GALP inhibits acute and long-term food intake . The reason for the observed difference in feeding in mice and rats is currently unclear, although some have suggested that the slightly different anatomical distribution of GALP and its receptor containing UNC 0631 in the Arc in mice and rats may play a role in the differential effects in these two species . This study is the first to examine a physiological role of GALP in a non-mammalian species. The results support our hypothesis that GALP is a functional neuroendocrine factor in fish, and adds GALP to the list of neuropeptides involved in the control of food intake in fish , , , , , , , . The presence of GALR1 and GALR2 in goldfish brain, especially in the hypothalamic nucleus (NLT) involved in the regulation of energy balance, suggests a direct action of GALP in goldfish brain
Conflict of interest
Galanin receptor agonists
Galanin receptor antagonists
Introduction Although the etiology of type 2 diabetes is not fully clear, it is recognized that increased insulin resistance in both skeletal muscles and adipocytes plays an important role in the pathogenesis of type 2 diabetes . Insulin-stimulated glucose uptake occurs about 85% in skeletal muscle and only 10% in adipose tissue, but the latter is very important for controlling whole-body energy homeostasis . Therefore, understanding the mechanism of glucose transport in both skeletal muscles and adipocytes is crucial for elucidating the etiology of type 2 diabetes. The neuropeptide galanin (GAL), a 29/30-amino-acid neuropeptide, exhibits anti-inflammatory, antidiabetic and antidyslipidemic effects , . GAL and its receptors are widely distributed in the central nervous system . A high density of GAL-immunoreactivity was found in the hypothalamus where a lot of nuclei relative to energy metabolism were distributed . A wealth of evidences indicate that central GAL is a critical regulator linking energy metabolism and glucose homeostasis , , . Firstly, an injection of GAL into paraventricular nucleus (PVN) significantly enhanced daily caloric intake, weight of fat depots, circulating non-esterified fatty acid content and lipoprotein lipase activity in adipose tissue, while reduced circulating glucose levels of rats . Besides, GLUT2 mRNA levels were decreased in GAL non-innervated cells but not in GAL-hyperinnervated cells, showing relatively normal glucose metabolism in the former compared with the latter . Oral administration of GAL improves glucose homeostasis and insulin sensitivity via the enteric nervous system . Most importantly, central GAL-mediated signals mediated the increase in energy expenditure and improved glucose metabolism and whole-body insulin sensitivity following AP1 antagonism in the ventral hypothalamus . Furthermore, GAL gene knockout mice displayed impaired glucose disposal due to reduced insulin response and insulin-independent glucose elimination , while the homozygous GAL transgenic mice showed reduced insulin resistance and increased metabolic rates of lipid and carbohydrate . Finally, our recent studies revealed that the i.c.v. injection of M35, a GAL antagonist, significantly increased insulin resistance and inhibited the glucose transporter 4 (GLUT4) translocation from intracellular membrane compartments to cell surfaces in myocytes and adipocytes of rats , . These results suggest that the central GALis important regulator for whole-body insulin sensitivity and energy homeostasis.