The potential role of adenosine in the pathophysiology of the insulin resistance syndrome.
An increased intracellular availability of the co-enzyme A esters of long-chain fatty acids is thought to underlie many aspects of the insulin resistance syndrome. However, the cause of clustering of a hyperdynamic circulation, sympathetic activation, hypertension, hyperuricaemia, and a raised haematocrit in the insulin resistance syndrome remains to be elucidated. We propose a mechanism that expands the etiological role of long-chain fatty acids. By inhibiting adenine nucleotide translocators, elevated intracellular concentrations of the co-enzyme A esters of long-chain fatty acids impair mitochondrial oxidative phosphorylation. This is expected to result in a chronic systemic increase in extracellular adenosine concentrations. As adenosine stimulates the sympathetic nervous system, induces systemic vasodilatation, stimulates erythropoiesis, and induces renal vasoconstriction with renal sodium retention, increased extracellular ADO concentrations may be the common denominator explaining the above-mentioned and still unexplained phenomena associated with the insulin resistance syndrome. Along the same lines, hyperuricaemia can be explained by the fact that adenosine is broken down to urate and because of increased renal urate retention.
Department of Internal Medicine, University Hospital Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands. s.j.l.bakker@int.azg.nl
S J
SJ
Bakker
R O
RO
Gans
J C
JC
ter Maaten
T
T
Teerlink
H V
HV
Westerhoff
R J
RJ
Heine
D000241:Adenosine / Q000502:physiology*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D004920:Erythropoiesis; D005227:Fatty Acids / Q000378:metabolism; D006339:Heart Rate; D006400:Hematocrit; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology; D006984:Hypertrophy; D007333:Insulin Resistance / Q000502:physiology*; D007515:Islets of Langerhans / Q000473:pathology / Q000503:physiopathology; D008928:Mitochondria / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D008954:Models, Biological; D009318:Natriuresis; D009765:Obesity / Q000378:metabolism; D010085:Oxidative Phosphorylation; D012079:Renal Circulation; D012307:Risk Factors; D012964:Sodium / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014527:Uric Acid / Q000097:blood; D014664:Vasodilation
D005227:Fatty Acids; D013481:Superoxides; D014527:Uric Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D012964:Sodium; D000241:Adenosine