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

Abstract

Alarin, a regulatory peptide, belongs to the galanin family and plays the same regulatory roles as galanin in orexigenic activity and energy metabolism. Our previous studies had found that galanin might facilitate insulin sensitivity via activation of its central receptors. To date, little is known about whether central alarin may exert similar effects on insulin sensitivity. In order to investigate this, alarin and its specific antagonist, alarin 6-25Cys, were administered into the cerebral ventricles of type 2 diabetic rats (T2DR) to evaluate the changes in insulin resistance. The results indicated that central treatment with alarin significantly increased the body weight of animals, the 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake, the plasma adiponectin levels, the glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, the vesicle-associated membrane protein 2 as well as glucose transporter 4 (GLUT4 (SLC2A4)) protein and mRNA levels, and the ratios of GLUT4 contents in plasma membranes to total cell membranes in adipocytes, but reduced blood glucose and plasma retinol-binding protein 4 levels. These effects of alarin may be inhibited by pretreatment with alarin 6-25Cys. The above-mentioned results suggest that the central alarin projective system may facilitate insulin sensitivity and glucose uptake via the increase in GLUT4 content and GLUT4 translocation from intracellular pools to plasma membranes in T2DR.

High Circulating Alarin Levels Are Associated with Presence of Metabolic Syndrome

“…These findings indicate that Alarin might have a regulatory role in glucose and lipid metabolism in vivo, consistent with the results of two animal studies [16,17]. Therefore, the elevation of circulating Alarin levels in MetS subjects might be beneficial to the improvement of metabolism in vivo.…”

“…In animal studies, the beneficial effects of Alarin on ameliorating insulin resistance, decreasing insulin levels and blood glucose have been revealed in the vivo and vitro [16,17]. However, the relationship between circulating Alarin and metabolic diseases has not been reported in humans.…”

“…Recently, Guo et al also demonstrated that central treatment of Alarin increased adiponectin release, 2-(N-7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino-2-deoxyglucose uptake, glucose transporter 4 (Glut4) mRNA expression and translocation on cell membrane. During the hyperinsulinemic-euglycemic clamp (EHC), glucose infusion rates (GIR) in ICV Alarin-treated rats were increased, whereas blood glucose level and retinol-binding protein 4 (RBP4) were reduced in diabetic rats [17]. Therefore, Alarin has been considered as a cytokine related insulin resistance and energy homeostasis.…”

The regulative effect of galanin family members on link of energy metabolism and reproduction

“…Alarin had no effect on body temperature compared to controls. Our recent study demonstrated that central treatment with alarin significantly increased the glucose uptake, the plasma adiponectin levels, the glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, the vesicle-associated membrane protein 2 as well as GLUT4 protein and mRNA levels, and the ratios of GLUT4 contents in plasma membranes to total cell membranes in adipocytes, but reduced blood glucose and plasma retinol-binding protein 4 levels [61]. The results suggest that the central alarin projective system may facilitate insulin sensitivity and glucose uptake via the increase in GLUT4 content and GLUT4 translocation from intracellular pools to plasma membranes in type 2 diabetic rats.…”

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

“…Alarin, a regulatory peptide, belongs to the galanin family and plays the same regulatory roles as galanin in orexigenic activity and energy metabolism (Fang et al, 2012b). Our recent study demonstrated that central treatment with alarin significantly increased the body weight of animals, the glucose uptake, the plasma adiponectin levels, the glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, the vesicle-associated membrane protein 2 as well as GLUT4 protein and mRNA levels, and the ratios of GLUT4 contents in plasma membranes to total cell membranes in adipocytes, but reduced blood glucose and plasma retinol-binding protein 4 levels (Guo et al, 2014). The above-mentioned results suggest that the central alarin projective system may facilitate insulin sensitivity and glucose uptake via the increase in GLUT4 content and GLUT4 translocation from intracellular pools to plasma membranes in type 2 diabetic rats (Guo et al, 2014).…”