The role of hyperglycemia in FAT/CD36 expression and function

Abstract

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.

Rac1-NADPH oxidase signaling promotes CD36 activation under glucotoxic conditions in pancreatic beta cells

“…Several studies have demonstrated that hyperglycemia-induced CD36 expression mediates cellular dysfunction in various tissues [28], [29]]. This upregulation was found to coincide with increased oxidative stress.…”

CD36: Implications in cardiovascular disease

“…Thiazolidinediones, a major new class of drugs to treat diabetes, up regulate CD36 in monocytes/macrophages, adipose and muscle (Wilmsen, Ciaraldi, Carter, Reehman, Mudaliar, & Henry, 2003, Kolak, et al, 2006, Hirakata, Tozawa, Imura, & Sugiyama, 2004,Llaverias, et al, 2006, and may therefore contribute to the insulin-sensitizing effects of these drugs as a result of plasma fatty acid clearance, but also potentially to atherosclerosis and obesity in these patients. Interestingly, glucose/insulin appears to increase CD36 expression (Sampson, Davies, Braschi, Ivory, & Hughes, 2003,Griffin, et al, 2001,Chabowski, et al, 2004,Chen, Yang, Loux, Georgeson, & Harmon, 2006, and because CD36 is expressed on tissues important in fatty acid metabolism (heart, skeletal muscle, fat, and in pathological states, liver) this may imply an important role for CD36 in insulin resistance (see later). Regulation of CD36 expression can be mediated both pre-and post-transcription.…”

Molecular Targets of Omega 3 and Conjugated Linoleic Fatty Acids – “Micromanaging” Cellular Response

“…Conversely, in human adipose tissue, both isomers induced decreased expression of this gene. It is noteworthy that plasma glucose levels play an important role in the regulation of CD36 expression in adipose tissue (Chen et al, 2006). CA3 (carbonic anhydrase 3) is a key enzyme in fatty acid synthesis that is downregulated by t10,c12 CLA in adipose tissue (Herrmann et al, 2009).…”