ArticleBiochimica et biophysica acta2014
Glucagon induces translocation of glucokinase from the cytoplasm to the nucleus of hepatocytes by transfer between 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase-2 and the glucokinase regulatory protein.
Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 26 citations in OpenAlex.
- Pancreatic α-cell sodium-glucose cotransporter 1 (SGLT1) does not appear to contribute to hyperglucagonemia and glucose intolerance in diabetic mice.Endocrine journal · 2026Article
- Morning glucagon disrupts insulin induced hepatic metabolic memory and subsequent afternoon glucose metabolism in canines.Frontiers in endocrinology · 2026Article
- Precision-cut liver slices as an ex vivo model to assess impaired hepatic glucose production.Communications biology · 2024Article
- Epac2 activation mediates glucagon-induced glucogenesis in primary rat hepatocytes.Journal of diabetes investigation · 2024Article
- The impact of glucagon to support postabsorptive glucose flux and glycemia in healthy rats and its attenuation in male Zucker diabetic fatty rats.American journal of physiology. Endocrinology and metabolism · 2024Article
- Current Insight on the Role of Glucokinase and Glucokinase Regulatory Protein in Diabetes.Mini reviews in medicinal chemistry · 2024Review
- Metabolic control analysis of hepatic glycogen synthesis in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Identification and functional analysis of GCK gene mutations in 12 Chinese families with hyperglycemia.Journal of diabetes investigation · 2019Article
- Molecular and cellular regulation of human glucokinase.Archives of biochemistry and biophysics · 2019Review
- Mechanisms of Insulin Action and Insulin Resistance.Physiological reviews · 2018Review
- Regulation of hepatic glucose metabolism in health and disease.Nature reviews. Endocrinology · 2017Review
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Glucokinase activity is a major determinant of hepatic glucose metabolism and blood glucose homeostasis. Liver glucokinase activity is regulated acutely by adaptive translocation between the nucleus and the cytoplasm through binding and dissociation from its regulatory protein (GKRP) in the nucleus. Whilst the effect of glucose on this mechanism is well established, the role of hormones in regulating glucokinase location and its interaction with binding proteins remains unsettled. Here we show that treatment of rat hepatocytes with 25mM glucose caused decreased binding of glucokinase to GKRP, translocation from the nucleus and increased binding to 6-phosphofructo 2-kinase/fructose 2,6 bisphosphatase-2 (PFK2/FBPase2) in the cytoplasm. Glucagon caused dissociation of glucokinase from PFK2/FBPase2, concomitant with phosphorylation of PFK2/FBPase2 on Ser-32, uptake of glucokinase into the nucleus and increased interaction with GKRP. Two novel glucagon receptor antagonists attenuated the action of glucagon. This establishes an unequivocal role for hormonal control of glucokinase translocation. Given that glucagon excess contributes to the pathogenesis of diabetes, glucagon may play a role in the defect in glucokinase translocation and activity evident in animal models and human diabetes.
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