Isoproterenol is a beta adrenergic agonist whose effects have been attributed to the generation of cAMP. Previous studies have shown that it inhibits glucose transport in adipocytes without changing the number of insulin-responsive glucose transporters (GLUT4) on the cell surface. However, we have shown previously that cAMP stimulates translocation of GLUT4 to the cell surface in adipocytes (Kelada et al. J Biol Chem 267, 7021-7025, 1992). We therefore further investigated the mechanisms involved in isoproterenol regulation of glucose transport. Consistent with the effects of dibutyryl cAMP, we found that a low concentration of isoproterenol (10 nM) stimulated glucose transport and the translocation of GLUT4 from the low density microsomal fraction to the plasma membrane. By contrast, a higher concentration of isoproterenol (1 microM) did not stimulate transport or GLUT4 translocation and furthermore inhibited dibutyryl cAMP-stimulated GLUT4 translocation. This inhibitory effect was specific for cAMP since isoproterenol had no effect on insulin-stimulated GLUT4 translocation. We conclude that isoproterenol has a biphasic effect on glucose transport, mediated by acute translocation of GLUT4 at low concentrations and by inhibition of intrinsic activity at high concentration, both of which may be explained by effects of cAMP. It has a further cAMP-independent effect at high concentration to inhibit cAMP-mediated translocation of GLUT4.

No abstract

Non-alcoholic fatty liver disease (NAFLD) represents one of the most common liver diseases. It is strongly associated with obesity and insulin resistance and thought to be parameters of the metabolic syndrome. NAFLD can progress to non-alcoholic steatohepatitis then to cirrhosis and liver failure. This study aimed to investigate whether silymarin or/and taurine can improve non-alcoholic fatty liver in an animal model and whether this therapeutic approach can result amelioration in carbohydrates profile (serum glucose, insulin, insulin resistance index and hepatic glycogen), lipids profile (serum cholesterol, triglycerides, free fatty acids, leptin and adiponectin as well as hepatic total lipids & cholesterol), liver function profile (serum aspartate transaminase, alanine transaminase, total protein, albumin and haptoglobin) and the cytokines profile (serum tumor necrosis factor-α, interleukin-1ß and interleukin-6). The obtained results revealed a significant (p<0.001) increase in carbohydrates profile (glucose, insulin, insulin resistance index & hepatic glycogen) in NAFLD rats than those in their control ones. Similary, lipid parameters (serum cholesterol, triglycerides, free fatty acids and leptin as well as hepatic total lipids & cholesterol) and liver function tests (serum aspartate transaminase, alanine transaminase and haptoglobin)were significantly (p<0.001) elevated in NAFLD rats compared with their corresponding control group. On the other hand, induction of NAFLD to rats caused a significant (p<0.001) decrease in adiponectin level with a remarkable decrease in serum total protein and albumin. A considerable (p<0.001) elevation were occurred in all cytokines parameters (serum tumor necrosis factor-α, interleukin-1ß and interleukin-6) in NAFLD rats group compared with their corresponding control group. When, NAFLD rats group was treated with silymarin or/and taurine, a considerable amelioration effects in all previous studied parameters were pronounced dependent on certain mechanisms and time of treatment. In conclusion, silymarin or/and taurine reduced metabolic abnormalities associated with NAFLD via inhibition the oxidative stress, increment in the stabilization of mitochondrial membrane, reduction the lipid accumulation in the liver, enhancement in the endoplasmic reticulum (ER) and improving insulin resistance. Overall, silymarin and taurine may be considered as promising and novel therapies for the treatment of NAFLD.