m-35 and Diabetes-Mellitus--Type-2

Although galanin has been shown to increase glucose transporter 4 (GLUT4) expression in skeletal muscle and adipocytes of rats, there is no literature available about the effect of galanin on GLUT4 expression in cardiac muscle of type 2 diabetic rats. In this study, we investigated the relationship between intracerebroventricular administration of M35, a galanin receptor antagonist, and GLUT4 expression in cardiac muscle of type 2 diabetic rats. The rats tested were divided into four groups: rats from healthy and type 2 diabetic drug groups were injected with 2 μM M35 for three weeks, while both control groups with 2 μl vehicle control. The euglycemic-hyperinsulinemic clamp test was conducted for an index of glucose infusion rates. The cardiac muscle was processed for determination of GLUT4 expression levels. The present study showed that the plasma insulin and retinol binding protein 4 (RBP4) levels were higher in both drug groups than controls respectively. Moreover, the results showed the inhibitive effect of central M35 treatment on glucose infusion rates in the euglycemic-hyperinsulinemic clamp test and GLUT4 expression levels in the cardiac muscle. These results demonstrate that endogenous galanin, acting through its central receptor, has an important attribute to increase GLUT4 expression, leading to enhance insulin sensitivity and glucose uptake in cardiac muscle of type 2 diabetic rats. Galanin and its fragment can play a significant role in regulation of glucose metabolic homeostasis in cardiac muscle and galanin is an important hormone relative to diabetic heart.

Topics: Animals; Blood Glucose; Bradykinin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Galanin; Gene Expression Regulation; Glucose Transporter Type 4; Humans; Insulin; Myocardium; Peptide Fragments; Rats; Receptors, Galanin; Retinol-Binding Proteins, Plasma

Although galanin has been shown to increase insulin sensitivity in skeletal muscle of rats, there is no literature available about the effect of galanin on Glucose Transporter 4 (GLUT4) translocation from intracellular membrane pools to plasma membranes in adipocytes of type 2 diabetic rats. In the present study M35, a galanin antagonist was used to elucidate whether exercise-induced galanin release increased GLUT4 translocation in adipocytes of streptozotocin-induced diabetic rats. The present findings showed that plasma galanin levels after swimming training in all four trained groups were higher compared with each sedentary control. M35 treatment had an inhibitory effect on glucose infusion rates in the euglycemic-hyperinsulinemic clamp test and GLUT4 mRNA expression levels in adipocytes. Moreover, M35 treatment reduced GLUT4 concentration in both plasma membranes and total cell membranes. The ratios of GLUT4 contents in plasma membranes to total cell membranes in four drug groups were lower compared with each control. These data demonstrate a beneficial role of endogenous galanin to transfer GLUT4 from internal stores to plasma membranes in adipocytes of type 2 diabetic rats. Galanin plays a significant role in regulation of glucose metabolic homeostasis and is an important hormone relative to diabetes.

Topics: Adipocytes, White; Animals; Bradykinin; Cell Fractionation; Cell Membrane; Diabetes Mellitus, Type 2; Epididymis; Galanin; Gene Expression Regulation; Glucose Transporter Type 4; Insulin Resistance; Male; Motor Activity; Peptide Fragments; Protein Precursors; Protein Transport; Random Allocation; Rats; Rats, Wistar; RNA, Messenger; Streptozocin; Swimming

The aim of this study is to investigate whether galanin (GAL) central receptors are involved in regulation of insulin resistance. To test it, a GAL antagonist, M35 was intracerebroventricularly administrated in trained type 2 diabetic rats. The euglycemic-hyperinsulinemic clamp test was conducted for an index of glucose infusion rates. The epididymal fat pads were processed for determination of glucose uptake and Glucose Transporter 4 (GLUT4) amounts. The Gal mRNA expression levels in hypothalamus were quantitatively assessed too. We found an inhibitory effect of M35 on glucose uptake into adipocytes, Gal mRNA expression levels in hypothalamus, glucose infusion rates in the clamp test and GLUT4 concentration in plasma membranes and total cell membranes of adipocytes. The ratios of GLUT4 contents of the former to the latter in M35 groups were lower. These results suggest a facilitating role for GAL on GLUT4 translocation and insulin sensitivity via its central receptors in rats.

Topics: Adipocytes; Animals; Blood Glucose; Body Weight; Bradykinin; Cell Membrane; Cholesterol; Deoxyglucose; Diabetes Mellitus, Type 2; Fasting; Galanin; Gene Expression Regulation; Glucose Clamp Technique; Glucose Transporter Type 4; Hypothalamus; Injections, Intraventricular; Insulin; Insulin Resistance; Male; Peptide Fragments; Physical Conditioning, Animal; Rats; Rats, Wistar; RNA, Messenger; Triglycerides

The aim of this study was to determine whether enhanced galanin (GAL) release induced by exercise would elevate insulin sensitivity and glucose transporter 4 (GLUT4) concentration in the plasma membranes of skeletal muscle in type 2 diabetic rats. We used M35, a GAL antagonist to antagonize the GAL function and swimming training for four weeks to increase GAL release of rats. The blood samples were analyzed for GAL and insulin concentration. The euglycemic-hyperinsulinemic clamp test was conducted for an index of glucose infusion rates. Additionally, skeletal muscle was collected and processed for GLUT4 mRNA level and GLUT4 concentration. The present findings showed that plasma GAL levels after swimming training in all three trained groups were higher compared with each sedentary control and each preswimming level. The insulin levels after swimming in both M35 treatment groups were elevated compared with each diabetic control and each pretraining level. Moreover, M35 treatment reduced glucose infusion rates compared with each diabetic control, but swimming enhanced the rates in all trained groups compared with each sedentary control. Furthermore, M35 treatment reduced GLUT4 concentration and GLUT4 mRNA levels compared with each diabetic control. The ratio of GLUT4 contents in plasma membranes to total cell membranes in both drug groups were lower compared with each diabetic control. These results suggest that endogenous GAL may enhance GLUT4 contents and promote GLUT4 transportation from intracellular membrane pools to plasma membranes. GAL is an important hormone to regulate insulin sensitivity in skeletal muscle from type 2 diabetic rats.

Topics: Analysis of Variance; Animals; Blood Glucose; Bradykinin; Cell Membrane; Diabetes Mellitus, Type 2; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Galanin; Gene Expression Regulation; Glucose Clamp Technique; Glucose Transporter Type 4; Insulin; Male; Muscle, Skeletal; Peptide Fragments; Physical Conditioning, Animal; Rats; Rats, Wistar; RNA, Messenger; Streptozocin; Swimming