Regulation of gene expression by glucose

Abstract

Fatty acid synthase (EC 2.3.1.85) is an enzyme involved in the lipogenic pathway allowing fatty acid synthesis from glucose. Glucose up-regulates the transcription of the fatty acid synthase gene in both adipocytes and hepatocytes, with insulin having only an indirect role. The signal metabolite could be glucose-6-phosphate rather than glucose itself. The glucose response element of the fatty acid synthase gene has not yet been precisely identified, although a −2 kb region of the fatty acid synthase promoter is sufficient to confer nutritional responsiveness to a reporter gene. ADD1/SREBP1, a b-HLH-LZ transcription factor belonging to the sterol regulatory element-binding protein family might be involved in the transduction of the glucose effect. Finally, the stimulatory effect of glucose on the expression of the fatty acid synthase gene is inhibited by the activation of AMP-activated protein kinase. Interestingly enough, AMP-activated protein kinase is structurally and functionally related to the yeast SNF1 protein kinase complex which is essential for the transcriptional activation of glucose-repressed genes in Saccharomyces cerevisiae.

VLDL Induces Adipocyte Differentiation in ApoE-Dependent Manner

“…In addition to classic LPL-dependent hydrolysis of VLDL, de novo synthesis of fat in adipocytes and energy expenditure also regulate adipogenesis. 42,43 The lipid composition of VLDL also affects adipogenesis (Figure 4). In fact, the apoE-dependent pathway is not the only adipogenic pathway working in our mouse model.…”

Glucose 6-Phosphate Hydrolysis Is Activated by Glucagon in a Low Temperature-sensitive Manner

“…Therefore, we may consider that one of the major roles of glucagon could be related to its effect on intracellular signaling molecules such as glucose 6-phosphate (51), as it was proposed for glucose-6-phosphatase (52). Indeed this metabolite could play a key role as a signaling molecule to transmit the effect of glucose on gene regulation (12,53). We have also suggested recently that glucose 6-phosphate could be a crucial signaling metabolite in the short term inhibition of hepatic glucose production under the action of insulin and hyperglycemia (54).…”

“…Therefore we propose glucagon to be involved in hepatic glucose 6-phosphate concentration by activating its hydrolysis in a temperature-dependent pathway. Hence this hormone could be involved in the glucose sensing by liver cells via its phosphorylated metabolite, glucose 6-phosphate, and in turn in the transcriptional effects of glucose (11,12). Such a finding could lead to reconsider the role of glucagon in the pathogenesis and treatment of type II diabetes.…”

“…Apart from these indisputable effects, a stimulation of glucose-6-phosphatase, a key enzyme in glucose production, has been proposed but never proven (8 -10). In view of a potential key role of glucose 6-phosphate as a cellular intermediate in the transcriptional effects of glucose (11,12), an effect of glucagon on glucose-6-phosphatase could be of major importance. Indeed, despite a prominent effect on liver glucose metabolism, the role of glucagon in the pathogenesis of type II diabetes is still unclear and a matter of debate (13).…”

Glucose induces increases in levels of the transcriptional repressor Id2 via the hexosamine pathway

“…Gene expression events induced by normal physiological fluctuations in glucose levels play a critical role in the maintenance of proper glucose and lipid homeostasis. These effects have been thoroughly investigated mostly in liver, where changes in glucose levels play an important role in switching off gluconeogenesis and switching on glycolytic pathways (15,17). Glucose also plays a key role in regulating the expression and release of insulin in the ␤-cells of the pancreas (45), and the insulin released subsequently plays an important role in the regulation of metabolic genes (17).…”