Skeletal muscle glucose uptake, glycogen synthase activity and GLUT 4 content during hypoglycaemia in type 1 diabetic

L Orskov1, O Schmitz, J F Bak

  • 1Department of Medicine C, Aarhus University Hospital, Denmark. L.Oerskov@dadlnet.dk

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.

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