ISSN:
1432-0428
Keywords:
Key words Type 1 (insulin-dependent) diabetes mellitus, gene expression, skeletal muscle, glycogen synthase, phosphofructokinase, hexokinase.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 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. In conclusion: 1) Reduced allosterical activation of glycogen synthase in muscle of Type 1 diabetic patients in poor metabolic control occurs in the presence of normal total activity as well as normal immunoreactive protein mass and mRNA level of glycogen synthase. 2) Changes in serum insulin within the physiological range play no role in the short-term regulation of glycogen synthase mRNA and protein abundance in muscle from Type 1 diabetic patients. [Diabetologia (1994) 37: 82–90]
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s001250050076
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