Expression of glycogen synthase and phosphofructokinase in muscle from type 1 (insulin-dependent) diabetic patients before and after intensive insulin treatment.
The aim of the present study was to determine whether short-term appropriate insulinization of Type 1 (insulin-dependent) diabetic patients in long-term poor glycaemic control (HbA1C > 9.5%) was associated with an adaptive regulation of the activity and gene expression of key proteins in muscle glycogen storage and glycolysis: glycogen synthase and phosphofructokinase, respectively. In nine diabetic patients biopsies of quadriceps muscle were taken before and 24-h after intensified insulin therapy and compared to findings in eight control subjects. Subcutaneous injections of rapid acting insulin were given at 3-h intervals to improve glycaemic control in diabetic patients (fasting plasma glucose decreased from 20.8 +/- 0.8 to 8.7 +/- 0.8 mmol/l whereas fasting serum insulin increased from 59 +/- 8 to 173 +/- 3 pmol/l). Before intensified insulin therapy, analysis of muscle biopsies from diabetic patients showed a normal total glycogen synthase activity but a 48% decrease (p = 0.006) in glycogen synthase fractional velocity (0.1 mmol/l glucose 6-phosphate) (FV0.1) and a 45% increase (p = 0.01) in the half-maximal activation constant of glycogen synthase (A0.5). The activity of phosphofructokinase and the specific mRNA and immunoreactive protein levels of both glycogen synthase and phosphofructokinase were similar in the two groups. The 2.8-fold increase in serum insulin levels and the halving of the plasma glucose level for at least 15 h were associated with a normalization of glycogen synthase fractional activity (FV0.1) and of the half-maximal activation constant (A0.5) whereas the enzyme activity of phosphofructokinase and the mRNA and protein levels of both glycogen synthase and phosphofructokinase remained normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Vestergaard
H
H
Steno Diabetes Center, Copenhagen, Denmark.
Andersen
P H
PH
Lund
S
S
Vedel
P
P
Pedersen
O
O
D000328:Adult; D001706:Biopsy; D004247:DNA / Q000032:analysis / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000201:enzymology*; D015870:Gene Expression / Q000187:drug effects*; D006006:Glycogen Synthase / Q000096:biosynthesis* / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010732:Phosphofructokinase-1 / Q000096:biosynthesis* / Q000378:metabolism; D012313:RNA / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012016:Reference Values; D014158:Transcription, Genetic / Q000187:drug effects
D007328:Insulin; D012333:RNA, Messenger; D012313:RNA; D004247:DNA; D006006:Glycogen Synthase; D006593:Hexokinase; D010732:Phosphofructokinase-1