Combined galanin with insulin improves insulin sensitivity of diabetic rat muscles

Abstract

Although administration of galanin or insulin alone may enhance insulin sensitivity and glucose transporter 4 (GLUT4) trafficking, their cooperative effect on insulin sensitivity is still unclear. In the present study, we evaluated the cooperative effect of both reagents compared with solitary treatment with galanin or insulin in type 2 diabetic rats. Galanin and/or insulin were injected singly or together into type 2 diabetic rats once a day for 15 days. The results indicated that coadministration of both reagents compared with treatment with galanin or insulin alone significantly increased glucose infusion rates in euglycemichyperinsulinemic clamp tests, 2-deoxy-[3 H]D-glucose contents, GLUT4 densities, and pAS160and protein kinase C activity levels, but reduced blood glucose and insulin levels, as well as retinol-binding protein 4 contents, and did not affect Glut4 (Slc2a4) mRNA expression levels in myocytes. The changes in the ratios of GLUT4 immunoreaction in plasma membranes to total cell membranes of myocytes were higher in the coadministrative group compared with either the insulin or the galanin group. These results indicate that cooperation of the two hormones plays a synergic role to improve GLUT4 translocation and insulin sensitivity. This finding indicates the possibility of combining galanin with insulin with the aim of obtaining better antidiabetic efficacy than that of the canonical treatment with insulin alone.

Akt2-Dependent Beneficial Effect of Galanin on Insulin-Induced Glucose Uptake in Adipocytes of Diabetic Rats

“…Our previous studies found that treatment with a galanin antagonist, M35, decreased GLUT4 translocation and glucose uptake in adipocytes, i.e., endogenous galanin can elevate GLUT4 translocation and glucose uptake in diabetic rats [2]. Furthermore, Bu et al found that galanin may benefit insulin-induced GLUT4 translocation and subsequent glucose uptake [5]. In line with these studies, the present results revealed that co-administration of galanin and insulin compared to treatment with either hormone individually significantly increased [ 3 H]2-DG influx and GLUT4 and VAMP2 translocation, but reduced blood glucose levels, further manifesting that injection of galanin can facilitate insulin-stimulating glucose uptake in the adipocytes of diabetic animals.…”

“…The six treatment groups were injected with galanin (1 nmol·kg -1 , i.v. reference to Bu’s experiment [5]), insulin glargine (2 U·kg -1 , s.c.) and MK-2206 (300 μg·kg -1 , i.v. reference to Li’s experiment [10]), either individually or in combination.…”

“…As a versatile peptide, galanin can modulate many physiological functions, particularly increases in food intake, body weight and adiposity in animals [4]. Recent reports indicated that galanin might boost insulin-induced glucose transporter 4 (GLUT4) translocation and subsequent glucose uptake via activation of the Akt/PKB pathway in both fat and muscle cells [5, 6]. The galanin receptor family comprises three members, GalR1-3 [5].…”

“…Recent reports indicated that galanin might boost insulin-induced glucose transporter 4 (GLUT4) translocation and subsequent glucose uptake via activation of the Akt/PKB pathway in both fat and muscle cells [5, 6]. The galanin receptor family comprises three members, GalR1-3 [5]. Both activated GalR1 and GalR3 may inhibit adenyl cyclase and decrease the cAMP level through Gi/o receptors, resulting in activation of Akt/PKB [5, 7].…”

“…The galanin receptor family comprises three members, GalR1-3 [5]. Both activated GalR1 and GalR3 may inhibit adenyl cyclase and decrease the cAMP level through Gi/o receptors, resulting in activation of Akt/PKB [5, 7]. Activated GalR2 may result in the hydrolysis of inositol phosphate and activation of atypical protein kinase C through the Gq/11 pathway to enhance intracellular Ca 2+ concentration.…”