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Skeletal muscle glucose uptake, glycogen synthase activity and GLUT 4 content during hypoglycaemia in type 1 diabetic
1Department of Medicine C, Aarhus University Hospital, Denmark. L.Oerskov@dadlnet.dk
Abstract:
In healthy subjects, hypoglycaemia induces a profound 80% reduction in skeletal muscle glucose uptake and a similar suppression of glycogen synthase activity. The aim of this study was to examine the efficacy of this counterregulatory mechanism in type 1 diabetic subjects, who are especially prone to hypoglycaemic incidents. Nine type 1 diabetic male subjects were examined twice; during 120 min of hyperinsulinaemic (1.5 mU x kg(-1) x min(-1)) euglycaemia followed by (i) 240 min of graded hypoglycaemia (glucose nadir 2.8 mM) or (ii) 240 min of euglycaemia. At 345-360 min a muscle biopsy was taken and indirect calorimetry was performed at 210-240 and 320-340 min. The sensitivity of glycogen synthase to glucose-6-P was reduced by hypoglycaemia, as shown by an increase in A0.5 for glucose-6-P (at 0.07 mmol/L) from 0.21+/-0.02 to 0.28+/-0.03 mM (p=0.06). Likewise, the fractional velocity for glycogen synthase was reduced by 25%; i.e. from 20.8+/-2.0 to 15.5+/-1.4% (p<0.05). Total glucose disposal was decreased during hypoglycaemia (5.3+/-0.6 vs. 8.3+/-0.7 mg x kg(-1) x min(-1) (euglycaemia), n = 9; p<0.05), primarily due to a reduction of non-oxidative glucose disposal (2.7+/-0.3 vs. 5.1+/-0.6 mg x kg(-1) x min(-1) (euglycaemia), n=7; p<0.05). Forearm arteriovenous glucose differences were decreased by 50% in the hypoglycaemic situation (0.7+/-0.1 vs. 1.4+/-0.3 mmol/L (320-340 min)), and counterregulatory hormonal responses seemed less conspicuous than described in healthy subjects. We conclude that hypoglycaemia induces decrements of forearm glucose uptake and glycogen synthase activity in type 1 diabetic subjects. The study indicates a decreased magnitude of these responses, but this remains to be confirmed.
Insights
Hypoglycaemia reduces skeletal muscle glucose uptake and glycogen synthase activity in type 1 diabetic patients, indicating a weakened counterregulatory response. These findings highlight potential risks for individuals with type 1 diabetes during low blood sugar events.
Area of Science:
- Endocrinology and Metabolism
- Diabetology
- Skeletal Muscle Physiology
Background:
- Hypoglycaemia (low blood sugar) significantly impairs glucose metabolism in healthy individuals.
- Type 1 diabetes patients are particularly susceptible to hypoglycaemic incidents.
- Understanding counterregulatory responses in type 1 diabetes is crucial for managing blood glucose.
Purpose of the Study:
- To investigate the effectiveness of counterregulatory mechanisms during hypoglycaemia in type 1 diabetic subjects.
- To assess the impact of hypoglycaemia on skeletal muscle glucose uptake and glycogen synthase activity in this population.
Main Methods:
- Nine male type 1 diabetic subjects underwent hyperinsulinaemic euglycaemia followed by either graded hypoglycaemia or sustained euglycaemia.
- Muscle biopsies were analyzed for glycogen synthase activity and sensitivity to glucose-6-phosphate.
- Indirect calorimetry and forearm glucose uptake measurements were performed.
Main Results:
- Hypoglycaemia reduced glycogen synthase sensitivity and fractional velocity in type 1 diabetic subjects.
- Total and non-oxidative glucose disposal were significantly decreased during hypoglycaemia.
- Forearm glucose uptake was reduced by approximately 50%, with less pronounced counterregulatory hormonal responses compared to healthy subjects.
Conclusions:
- Hypoglycaemia leads to reduced forearm glucose uptake and impaired glycogen synthase activity in type 1 diabetic individuals.
- The magnitude of these counterregulatory responses appears diminished in type 1 diabetes compared to healthy controls.
- Further research is needed to confirm the reduced magnitude of these responses in type 1 diabetes.