AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise

Diabetes. 2001 May;50(5):921-7. doi: 10.2337/diabetes.50.5.921.

Abstract

Insulin-stimulated GLUT4 translocation is impaired in people with type 2 diabetes. In contrast, exercise results in a normal increase in GLUT4 translocation and glucose uptake in these patients. Several groups have recently hypothesized that exercise increases glucose uptake via an insulin-independent mechanism mediated by the activation of AMP-activated protein kinase (AMPK). If this hypothesis is correct, people with type 2 diabetes should have normal AMPK activation in response to exercise. Seven subjects with type 2 diabetes and eight matched control subjects exercised on a cycle ergometer for 45 min at 70% of maximum workload. Biopsies of vastus lateralis muscle were taken before exercise, after 20 and 45 min of exercise, and at 30 min postexercise. Blood glucose concentrations decreased from 7.6 to 4.77 mmol/l with 45 min of exercise in the diabetic group and did not change in the control group. Exercise significantly increased AMPK alpha2 activity 2.7-fold over basal at 20 min in both groups and remained elevated throughout the protocol, but there was no effect of exercise on AMPK alpha1 activity. Subjects with type 2 diabetes had similar protein expression of AMPK alpha1, alpha2, and beta1 in muscle compared with control subjects. AMPK alpha2 was shown to represent approximately two-thirds of the total alpha mRNA in the muscle from both groups. In conclusion, people with type 2 diabetes have normal exercise-induced AMPK alpha2 activity and normal expression of the alpha1, alpha2 and beta1 isoforms. Pharmacological activation of AMPK may be an attractive target for the treatment of type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AMP-Activated Protein Kinases
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Enzyme Activation
  • Exercise / physiology*
  • Gene Expression Regulation, Enzymologic
  • Glucose Transporter Type 4
  • Glycated Hemoglobin / analysis
  • Glycogen / metabolism
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Monosaccharide Transport Proteins / metabolism
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Muscle Proteins*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiology
  • Muscle, Skeletal / physiopathology*
  • Physical Exertion / physiology*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Messenger / genetics
  • Reference Values
  • Rest / physiology
  • Transcription, Genetic

Substances

  • Blood Glucose
  • Glucose Transporter Type 4
  • Glycated Hemoglobin A
  • Monosaccharide Transport Proteins
  • Multienzyme Complexes
  • Muscle Proteins
  • RNA, Messenger
  • SLC2A4 protein, human
  • Glycogen
  • PRKAA2 protein, human
  • PRKAB1 protein, human
  • Protein Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • PRKAA1 protein, human