The role of hyperglycemia in FAT/CD36 expression and function.
FAT/CD36 is a long-chain fatty acid transporter and scavenger receptor for oxidized LDL. Defects in FAT/CD36 have been linked to the hypertriglyceridemia and insulin resistance. Expression of FAT/CD36 was reported increase in type 1 diabetes; however, it remains unclear whether serum glucose or insulin plays an important role in this regulation. To elucidate the individual contribution of plasma glucose and insulin in the regulation of FAT/CD36 mRNA expression, we induced type 1 diabetes in male Sprague-Dawley rats using streptozotocin (STZ) and compared traditional insulin treatment with administration of the orally absorbed chemical agent vanadate, which reduces blood glucose levels via mechanisms that bypass insulin receptor action. STZ-exposed animals showed significant decreases in body weight (285.5 +/- 2.8 vs. 233.1 +/- 3.5 g, P < 0.001) and serum insulin levels (9.7 +/- 0.7 vs. 2.8 +/- 0.6 microU/ml, P < 0.05), accompanied by significant increases in blood glucose (71 +/- 3 vs. 433 +/- 11 mg/dl, P < 0.001), water intake (38.9 +/- 0.9 vs. 205.9 +/- 3.3 ml/day, P < 0.001) and food intake (22.0 +/- 0.4 vs. 36.9 +/- 1.0 g/day, P < 0.001). Diabetic animals demonstrated significant increases in FAT/CD36 mRNA levels in duodenum (2.2-fold), jejunum (1.8-fold), ileum (1.5-fold), adipose tissue (1.7-fold), and heart (2.5-fold) (P < 0.05). Insulin treatment reversed body weight loss and corrected hyperglycemia at diabetic rats as expected. Insulin treatment also corrected increased FAT/CD36 mRNA expression at diabetic rats. Vanadate significantly reduced serum glucose levels without increasing serum insulin or affecting body weight but reversed increased FAT/CD36 mRNA expression in diabetic rats. These data suggest that plasma glucose levels play more important role in the regulation of FAT/CD36 expression than concurrent changes in plasma insulin.
Chen
Min
M
Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Yang
Ying-Kui
YK
Loux
Tara J
TJ
Georgeson
Keith E
KE
Harmon
Carroll M
CM
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D001835:Body Weight; D018955:CD36 Antigens / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005786:Gene Expression Regulation; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D047495:PPAR gamma / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D014638:Vanadates / Q000627:therapeutic use
D001786:Blood Glucose; D018955:CD36 Antigens; D004791:Enzyme Inhibitors; D007328:Insulin; D047495:PPAR gamma; D012333:RNA, Messenger; D014638:Vanadates; D013311:Streptozocin