Demonstration of defective glucose uptake and storage in erythrocytes from non-insulin dependent diabetic patients and effects of metformin.
1. Red blood cells can store glucose and may thus participate in blood glucose homeostasis. We investigated if a defect in this process exists in non-insulin dependent diabetes (NIDD). 2. Blood was obtained in fasting conditions from 10 normal and 10 newly diagnosed NIDD patients (before and after 4 weeks Metformin therapy). Washed erythrocytes were resuspended in media containing various glucose concentrations (4.4, 6.6, 8.8 and 13.2 mmol/L). Total glucose uptake was calculated as the sum of the measurements of lactate as well as free glucose, the latter being determined before and after addition of amyloglucosidase to the pellet. 3. Cells from diabetics showed a pronounced reduction in glucose uptake, particularly in their capacity to store glucose as glycogen (reactive to amyloglucosidase). Metformin treatment almost normalized glycogen levels, whereas lactate declined concomitantly in the pellet. 4. Our data demonstrate that a defect in glucose uptake exists in erythrocytes from NIDD patients, affecting both free and stored glucose, and that this defect is reversed by Metformin treatment, indicating that this drug can increase glycogen levels even in insulin-insensitive cells. 5. Thus, in view of their total mass, erythrocytes may be important in the impaired glucose homeostasis in NIDD, in particular in marked hyperglycaemia such as after a meal.
Yoa
R G
RG
Department of Clinical Pharmacy, Faculty of Medicine and Pharmacy of Dijon, France.
Rapin
J R
JR
Wiernsperger
N F
NF
Martinand
A
A
Belleville
I
I
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged
D007773:Lactates; D019344:Lactic Acid; D006003:Glycogen; D008687:Metformin; D005947:Glucose