UNCHANGED GENE-EXPRESSION OF GLYCOGEN-SYNTHASE IN MUSCLE FROM PATIENTS WITH NIDDM FOLLOWING SULFONYLUREA-INDUCED IMPROVEMENT OF GLYCEMIC CONTROL

We have previously shown that the mRNA expression of muscle glycogen s ynthase is decreased in non-insulin-dependent diabetic (NIDDM) patient s; the objective of the present protocol was to examine whether the ge ne expression of muscle glycogen synthase in NIDDM is affected by chro nic sulphonylurea treatment. Ten obese patients with NIDDM were studie d before and after 8 weeks of treatment with a weight-maintaining diet in combination with the sulphonylurea gliclazide. Gliclazide treatmen t was associated with significant reductions in HbA(1C) (p = 0.01) and fasting plasma glucose (p = 0.005) as well as enhanced beta-cell resp onses to an oral glucose load. During euglycaemic, hyperinsulinaemic c lamp (2 mU . kg(-1). min(-1)) in combination with indirect calorimetry , a 35% (p = 0.005) increase in whole-body insulin-stimulated glucose disposal rate, predominantly due to an increased nonoxidative glucose metabolism (p = 0.02) was demonstrated in the gliclazide-treated patie nts when compared to pre-treatment values. In biopsies obtained from v astus lateralis muscle during insulin infusion, the half-maximal activ ation of glycogen synthase was achieved at a significantly lower conce ntration of the allosteric activator glucose 6-phosphate (p = 0.01). H owever, despite significant increases in both insulin-stimulated non-o xidative glucose metabolism and muscle glycogen synthase activation in gliclazide-treated patients no changes were found in levels of glycog en synthase mRNA or immunoreactive protein in muscle. In conclusion, i mproved blood glucose control in gliclazide-treated obese NIDDM patien ts has no impact on the gene expression of muscle glycogen synthase.