ABSTRACT
Although the discovery of glycogen in the liver, attributed to Claude Bernard, happened more than 160 years ago, the mechanism involved in the initiation of glucose polymerization remained unknown. The discovery of glycogenin at the core of glycogen's structure and the initiation of its glucopolymerization is among one of the most exciting and relatively recent findings in Biochemistry. This review focuses on the initial steps leading to the seminal discoveries of proteoglycogen and glycogenin at the beginning of the 1980s, which paved the way for subsequent foundational breakthroughs that propelled forward this new research field. We also explore the current, as well as potential, impact this research field is having on human health and disease from the perspective of glycogen storage diseases. Important new questions arising from recent studies, their links to basic mechanisms involved in the de novo glycogen biogenesis, and the pervading presence of glycogenin across the evolutionary scale, fueled by high throughput -omics technologies, are also addressed.
Subject(s)
Glucosyltransferases/metabolism , Glycogen/metabolism , Glycoproteins/metabolism , Animals , Glucose/metabolism , Glucosyltransferases/chemistry , Glucosyltransferases/genetics , Glycogen/chemistry , Glycogen Storage Disease/enzymology , Glycogen Storage Disease/genetics , Glycogen Storage Disease/metabolism , Glycoproteins/chemistry , Glycoproteins/genetics , Glycosylation , Humans , Liver/enzymology , Liver/metabolism , PolymerizationABSTRACT
PURPOSE: Industrial trans fatty acid (TFA) intake leads to impaired glucose metabolism. However, the overall effects reported are inconsistent and vary with the dietary FA composition and TFA isomer type and levels. We investigated TFA effects on glucose uptake, incorporation and oxidation, and glycogen synthesis in incubated soleus muscle under basal conditions or after treatment with insulin and/or palmitate. METHODS: Male Wistar rats were fed either linoleic acid (LA)-enriched (+LA) or LA-deprived (-LA) diet, supplemented (+LA + TFA or -LA + TFA) or not with TFA, for 60 days. Soleus muscle glucose metabolism was assessed in the absence or presence of insulin and/or palmitic acid. RESULTS: Under basal conditions, TFA enhanced glucose uptake and oxidation regardless of the LA status. Both TFA-supplemented groups had lower insulin response to glucose metabolism. Under insulin-stimulated conditions, TFA prevented the palmitate inhibition of muscle glucose uptake and metabolism in the +LA + TFA group. CONCLUSION: Dietary TFA enhanced glucose utilization in incubated soleus muscle under basal conditions and prevented the palmitate-induced inhibition in insulin-stimulated conditions. However, TFA reduced the insulin response to glucose uptake and metabolism. The effects mentioned above were influenced by the FA profile modifications induced by the dietary LA levels, suggesting that lipid metabolization and incorporation into plasma membrane are important determining factors of glucose metabolism and insulin sensitivity.
Subject(s)
Glucose/metabolism , Linoleic Acid/pharmacology , Muscle, Skeletal/metabolism , Trans Fatty Acids/pharmacology , Animals , Diet , Fatty Acids , Insulin , Male , Rats , Rats, Wistar , Trans Fatty Acids/chemistryABSTRACT
The effect that conjugated linoleic acid (CLA) has on glucose metabolism in experimental animals depends on nutritional conditions. Therefore, we hypothesized that CLA improves glucose utilization and insulin sensitivity in rats fed different levels of dietary linoleic acid (LA). We investigated the effect of CLA on the uptake, incorporation, and oxidation of glucose and glycogen synthesis in the soleus muscle of rats who were fed either LA-enriched (+LA) or LA-deprived (-LA) diets, under basal conditions and in the absence or presence of insulin and/or palmitate. For 60 days, male Wistar rats were fed 1 of 4 diets consisting of +LA, -LA, or +LA and -LA supplemented with CLA. Nutritional parameters and soleus glucose metabolism were evaluated. Under basal conditions, CLA enhanced soleus glucose oxidation, whereas increased glucose uptake and incorporation were observed in the -LA + CLA group. Conjugated linoleic acid-supplemented rats presented a lower response to insulin on glucose metabolism compared with non-CLA-supplemented rats. Palmitate partially inhibited the effect of insulin on the uptake and incorporation of glucose in the +LA and -LA groups but not in the +LA + CLA or -LA + CLA groups. Dietary CLA increased glucose utilization under basal conditions and prevented the palmitate-induced inhibition of glucose uptake and incorporation that is stimulated by insulin. The beneficial effects of CLA were better in LA-deprived rats. Conjugated linoleic acid may also have negative effects, such as lowering the insulin response capacity. These results demonstrate the complexities of the interactions between CLA, palmitate, and/or insulin to differentially modify muscle glucose utilization and show that the magnitude of the response is related to the dietary LA levels.