Blocking central galanin receptors attenuates insulin sensitivity in myocytes of diabetic trained rats

Abstract

Galanin (Gal), a bioactive neuropeptide, is widely distributed throughout the central nervous system and has diverse modulatory effects. To understand the central effect of this training-stimulatory peptide on insulin sensitivity, its antagonist M35 was injected into the cerebral ventricle in type 2 diabetic rats. A treadmill running of the rats was used to stimulate circulating Gal secretion and central Gal mRNA expression. The results showed that M35 significantly decreased glucose infusion rates in euglycemic-hyperinsulinemic clamp tests as well as 2-deoxy-[(3) H]D-glucose uptake and peroxisome proliferator-activated receptor-α expression levels in skeletal muscles. M35 also attenuated glucose transporter 4 (GLUT4) concentration in plasma membranes and total cell membranes of myocytes, and the ratios of the GLUT4 contents in the former to the latter in M35 groups were lower than those of each diabetic control. These results imply that endogenous Gal, acting through its central receptor, may facilitate GLUT4 translocation from cytoplasm vesicles to cellular surface of myocytes to accelerate glucose uptake and to enhance insulin sensitivity in healthy and type 2 diabetic rats. Gal and its relative agents are potential targets for treatment of type 2 diabetes mellitus and its complications.

Association between circulating levels of galanin and pre-pregnancy body mass index in patients with gestational diabetes mellitus

“…GDM is well established to result in decreased insulin sensitivity, impaired glucose tolerance and subsequently diabetes mellitus. Since galanin was shown to improve glucose tolerance in animals (Bu et al, 2013;He et al, 2011;Liang et al, 2012;Zhang et al, 2012), the observed high values of galanin in GDM subjects may also represent a physiological attempt to restore glucose tolerance, a hypothesis that warrants future investigations. SHBG is a glycoprotein possessing high affinity binding for 17 betahydroxysteriod hormones and involving in transport of sex steroids in plasma (Selby, 1990).…”

“…These data seem to indicate that the higher galanin level may be a consequence of elevated glucose, because higher level of plasma galanin is positively correlated with higher level of blood glucose in the pregnant women with GDM. Administration of galanin antagonist regulated circulating glucose levels by stimulating glucose uptake through the increase of GLUT4 expression and the acceleration of the translocation of GLUT4 to the plasma membrane of various insulin-sensitive cells in animals (Bu et al, 2013;He et al, 2011;Liang et al, 2012;Zhang et al, 2012). Furthermore, coadministration of both galanin and insulin compared with respective treatment with galanin or insulin significantly increased GLUT4 protein levels in myocytes of type 2 diabetic rats (Bu et al, 2014).…”

“…During a glucose tolerance test, galanin secretion is positively correlative with the blood glucose level in healthy volunteers, patients with type 2 diabetes, and pregnant women with gestational diabetes mellitus under fasting states (Fang et al, 2013a;Fang et al, 2013b;Legakis et al, 2005;Legalkis et al, 2007). Finally, galanin itself may have a central or permissive role in the pathogenesis of insulin resistance and type 2 diabetes by increasing the glucose uptake of skeletal muscle and adipose tissues (Bu et al, 2013;He et al, 2011;Liang et al, 2012;Zhang et al, 2012), consequently improving insulin sensitivity. Therefore, these studies provide convincing evidence that galanin is an important hormone to elevate energy metabolism and to promote glucose transportations in humans and animals.…”

Central alarin ameliorated insulin resistance of adipocytes in type 2 diabetic rats

“…Recently, we and others have found that central galanin may facilitate GLUT4 translocation and insulin sensitivity in healthy and type 2 diabetic rats (T2DR) , Liang et al 2012, Bu et al 2013. However, little is known as to whether central alarin is involved in a similar role of ameliorating insulin resistance.…”

Elevated galanin may predict the risk of type 2 diabetes mellitus for development of Alzheimer’s disease

“…Finally, our and other's recent studies demonstrated that administration of M35, a galanin antagonist, reduced 2-deoxy-[3H]-D-glucose (2-DG) content in myocytes and adipocytes as well as glucose infusion rates in the hyperinsulinemic-euglycemic clamp test, which was a direct assessment of insulin sensitivity in healthy and type 2 diabetic rats (Bu et al, 2013;Fang et al, 2014c;Guo et al, 2011;He et al, 2011;Jiang et al, 2009;Liang et al, 2012;. By contrast, our recent study demonstrated that administration of M617, a GalR1 agonist, increased insulin sensitivity in healthy and type 2 diabetic rats (Fang et al, 2014d).…”