Effects of glipizide on glucose metabolism and muscle content of the insulin-regulatable glucose transporter (GLUT 4) and glycogen synthase activity during hyperglycaemia in type 2 diabetic patients.
To examine whether sulphonylureas influence hyperglycaemia-induced glucose disposal and suppression of hepatic glucose production (HGP) in type 2 diabetes mellitus, a 150-min hyperglycaemic (plasma glucose 14 mmol/l) clamp with concomitant somatostatin infusion was used in eight type 2 diabetic patients before and after 6 weeks of glipizide (GZ) therapy. 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 improved 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 significant increase in the immunoreactive abundance of the insulin-regulatable glucose transport protein (GLUT 4) (P < 0.02). In conclusion, these results suggest that GZ therapy in type 2 diabetic patients enhances hepatic sensitivity to hyperglycaemia, while glucose-induced glucose uptake remains unaffected. In addition, GZ tends to normalize the activity of glycogen synthase and increases the content of GLUT 4 protein in skeletal muscle.
Schmitz
O
O
Medical Department M (Endocrinology and Diabetes), Aarhus Kommunehospital, Denmark.
Lund
S
S
Bak
J F
JF
Orskov
L
L
Andersen
P H
PH
Møller
N
N
Rasmussen
O
O
Christiansen
J S
JS
Pedersen
O
O
D000328:Adult; D001706:Biopsy; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005913:Glipizide / Q000494:pharmacology* / Q000627:therapeutic use; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D051275:Glucose Transporter Type 4; D006006:Glycogen Synthase / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins; D009132:Muscles / Q000378:metabolism
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495692:SLC2A4 protein, human; D005934:Glucagon; D006006:Glycogen Synthase; D005947:Glucose; D005913:Glipizide