Gliclazide treatment of streptozotocin diabetic rats restores GLUT4 protein content and basal glucose uptake in skeletal muscle.
This study examined whether the treatment of streptozotocin (STZ)-diabetic rats with gliclazide (5 mg/kg body weight twice daily orally) increases muscle glucose uptake. Rats were treated (group G, n = 10) or untreated (group D, n = 11) for 12 days. Normal rats served as controls (group C, n = 11). At the end of the treatment, both basal and insulin-stimulated glucose uptake by the perfused hindquarters were measured. In gastrocnemious muscles, the protein content of GLUT4 and the insulin binding and tyrosine kinase activity of partially purified solubilized insulin receptors were measured. Group G had a lower mean glycemic value during the treatment period than group D (mean +/- SEM, 17 +/- 0.6 v 19.7 +/- 0.5 mmol/L, P < .05), without differences in serum insulin levels. Basal glucose uptake by the hindquarters was significantly higher in group G versus group D (2.8 +/- 0.3 v 1.3 +/- 0.2 mumol/g/h, P < .05), and was not different versus group C (3.6 +/- 0.2 mumol/g/h). Insulin-stimulated glucose uptake was higher (P < .05) in group C compared with the two groups of diabetic rats. Glucose uptake at 10(-7) mol/L insulin was higher in group G than in group D (9.2 +/- 0.6 v 7.0 +/- 0.6 mumol/g/h, P < .05). Both insulin binding and tyrosine kinase activity were similar in muscle insulin receptors from both groups of diabetic rats. The GLUT4 protein content was higher in group G than in group D (95 +/- 10 v 57 +/- 7 arbitrary units [AU]/microgram protein, P < .05) and similar to that of group C (113 +/- 13 AU/microgram protein). In conclusion, gliclazide has a glucose-lowering effect in STZ-diabetic rats that could be attributed to an increase in muscle glucose clearance by a post-insulin receptor mechanism, probably related to a normalization of GLUT4 content.
Pulido
N
N
Department of Endocrinology, Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spain.
Suarez
A
A
Casanova
B
B
Romero
R
R
Rodriguez
E
E
Rovira
A
A
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005907:Gliclazide / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics*; D051275:Glucose Transporter Type 4; D006614:Hindlimb; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000032:analysis* / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000032:analysis / Q000378:metabolism; D013311:Streptozocin
D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D007457:Iodine Radioisotopes; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D013311:Streptozocin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D005907:Gliclazide; D005947:Glucose