Significance of the Randle-Mechanism in the etiology of diabetes type II.
In 1963, Randle, Garland, Hales and Newsholme proposed the existence of a glucose fatty-acid cycle in which excess lipid oxidation leads to inhibition of glucose oxidation in muscle tissue. Calorimetric studies confirmed these observations in man. However, as the rate of glucose oxidation is limited in the resting state, a defect in glucose oxidation can only have limited effects on glucose tolerance. The demonstration, by our group, of inhibition of glucose storage following increased lipid oxidation has suggested that excess lipids might induce glucose intolerance through an inhibitory effect on glucose storage. This might be explained by a decrease in glycogen mobilization (a factor that regulates glucose storage) as a consequence of the inhibition of glucose oxidation by excess fatty acids, according to Randle. In obesity, the resistance to glucose storage is present as a constant phenomenon. It is overcome by adaptation of the glycemic response to carbohydrate ingestion. This rise in glycemia, appearing as impaired glucose tolerance, allows glucose to be stored in spite of the resistance to glucose storage. But, simultaneously, this rise in glycemia decreases the possibility for glycogen mobilization, thus further limiting glucose storage. With the duration of obesity and the persistence of the hyperlipacidemia, when the glycemic response to a meal does not return any more to basal levels, the capacity for glucose storage becomes markedly impaired, so that glucose intolerance reaches the stage of diabetes. In type II diabetes of the obese, decrease in insulin response appears a late phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)
Felber
J P
JP
Département de Médecine Interne, Centre Hospitalier, Universitaire Vaudois, Lausanne, Switzerland.
D000273:Adipose Tissue / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D009132:Muscles / Q000378:metabolism; D009765:Obesity; D010084:Oxidation-Reduction
D001786:Blood Glucose; D005227:Fatty Acids; D005947:Glucose