EFFECTS OF GLIPIZIDE ON GLUCOSE-METABOLISM AND MUSCLE CONTENT OF THE INSULIN-REGULATABLE GLUCOSE-TRANSPORTER (GLUT-4) AND GLYCOGEN-SYNTHASEACTIVITY DURING HYPERGLYCEMIA IN TYPE-2 DIABETIC-PATIENTS

To examine whether sulphonylureas influence hyperglycaemia-induced glu cose disposal and suppression of hepatic glucose production (HGP) in t ype 2 diabetes mellitus, a 150-min hyperglycaemic (plasma glucose 14 m mol/l) clamp with concomitant somatostatin infusion was used in eight type 2 diabetic patients before and after 6 weeks of glipizide (GZ) th erapy. During the clamp a small replacement dose of insulin was given (0.15 mU/kg per min). Isotopically determined glucose-induced glucose uptake was similar before and after GZ administration which led to imp roved glycaemic control (basal plasma glucose 12.2 +/- 1.3 vs 8.9 +/- 0.7 mmol/l; P < 0.01). Glucose-induced suppression of HGP was, however , more pronounced during GZ treatment (0.96 +/- 0.14 vs 1.44 +/- 0.20 mg/kg per min; P < 0.02). Following GZ treatment hyperglycaemia failed to stimulate glycogen synthase activity. Moreover, GZ resulted in a s ignificant increase in the immunoreactive abundance of the insulin-reg ulatable glucose transport protein (GLUT 4) (P < 0.02). In conclusion, these results suggest that GZ therapy in type 2 diabetic patients enh ances hepatic sensitivity to hyperglycaemia, while glucose-induced glu cose uptake remains unaffected. In addition, GZ tends to normalize the activity of glycogen synthase and increases the content of GLUT 4 pro tein in skeletal muscle.