Disease relevance of Gyk

• Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase [1].
• Glycerol kinase activity in adenoma alveolar type II cells [2].
• Arterial delivery of an adenovirus harboring glycerol kinase cDNA allowed us to observe glycerol-stimulated insulin secretion from mouse islets, which was not observed when we employed the conventional method [3].
• Hyperinsulinemia and fat cell glycerokinase activity in obese (ob/ob) and diabetic (db/db) mice [4].

High impact information on Gyk

• TZDs trigger the dismissal of corepressor histone deacetylase (HDAC) complexes and the recruitment of coactivators to the GyK gene [5].
• TZDs also induce PPARgamma-Coactivator 1alpha (PGC-1alpha), whose recruitment to the GyK gene is sufficient to release the corepressors [5].
• Many PPARgamma target genes are induced during adipogenesis, but others, such as glycerol kinase (GyK), are expressed at low levels in adipocytes and dramatically up-regulated by TZDs [5].
• A series of our results indicate that AQP7 disruption elevates adipose glycerol kinase activity, accelerates triglycerides synthesis in adipocytes, and, finally, develops obesity [1].
• Isolated glycerol kinase deficiency has an inconstant phenotype, ranging from asymptomatic hyperglycerolemia to a severe metabolic disorder with growth and psychomotor retardation [6].

Chemical compound and disease context of Gyk

• Recent studies have shown that the absence of AQP7 expression in fat cells increases glycerol kinase activity, boosting triacylglycerol synthesis and ultimately leading to obesity [7].

Biological context of Gyk

• We report a tissue-dependent response to Gyk gene deletion [8].
• Northern blot analysis revealed that both forms of the murine ortholog, Gyk, were highly expressed in murine heart and increased during embryonic development [9].
• Under conditions of Gyk deficiency, we speculate that glycerol-3-phosphate and lipid production is maintained via alternative biosynthesis, including glycolysis, glyceroneogenesis, or by direct acylation of glycerol in brain, muscle, kidney, and liver, but not in heart [8].
• The activities of either the mitochondrial or cytosolic glycerol phosphate dehydrogenase (mGPD, cGPD) plus that of glycerol kinase are required for the use of glycerol in aerobic metabolism and gluconeogenesis [10].
• These mice share some features of both glycerol kinase deficiency and hereditary fructose intolerance, suggesting the phenotype may be due to the combined effects of the loss of a gluconeogenic substrate, the osmotic effects of glycerol, and the metabolic effects of the accumulation of a phosphorylated metabolite [10].

Anatomical context of Gyk

• We demonstrated the enhanced glycerol kinase enzymatic activity in Aqp7-KO and -knockdown adipocytes [1].
• The neuronal metabolism of glycerol, which was confirmed in experiments with purified synaptosomes and cultured cerebellar granule cells, suggested neuronal expression of glycerol kinase and some isoform of glycerol-3-phosphate dehydrogenase [11].
• Adipose tissue glycerokinase activity in genetic and acquired obesity in rats and mice [12].

Associations of Gyk with chemical compounds

• Compared with young mature adipocytes, older cells are increasingly insulin resistant, have decreased glucose uptake and fuel consumption, and show impaired glycerokinase-mediated fatty acid reesterification [13].
• In the glycerol assay, glycerol is phosphorylated with [32P]ATP and glycerokinase, residual [32P]ATP is hydrolyzed by heating in acid, and free [32P]phosphate is removed by precipitation with ammonium molybdate and triethylamine [14].
• Glycerokinase activity and triacylglycerol content in hearts of genetically obese hyperglycemic (ob/ob) mice [15].
• (+/-)2,3-Dihydroxypropyl dichloroacetate, an inhibitor of glycerol kinase [16].
• In the thin C57BL/6J mice, the activities of two alpha-glycerophosphate-generating enzymes i.e., glycerokinase (GK) and alpha-glycerophosphate dehydrogenase (GDH), increased in BAT at cold exposure [17].

Other interactions of Gyk

• Glycerol kinase deficiency in humans occurs as an isolated enzyme deficiency or as part of a contiguous gene deletion syndrome in variable association with Duchenne muscular dystrophy and adrenal hypoplasia congenita [6].
• The radiometric glucose assay is similar to the glycerol assay, except that glucokinase is used instead of glycerokinase [14].

Analytical, diagnostic and therapeutic context of Gyk

• To understand better the physiological significance of glycerol kinase and the pathophysiology of its deficiency, we generated glycerol kinase-deficient mice by gene targeting [6].
• In the other forms of acquired and genetic obesity in the rats and mice studied (also associated with hyperinsulinemia), adipose tissue glycerokinase activity was not elevated in comparison to lean control groups when expressed on a mg protein basis [12].
• Our studies in two animal models of this disease (GK rat and ob/ob mouse) suggest that an impaired glucose metabolism may be a primary defect in the stimulus-secretion coupling in the beta-cells in Type 2 diabetes [18].

References