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Haeusler RA, Camastra S, Astiarraga B, et al. Decreased expression of hepatic glucokinase in type 2 diabetes. Mol Metab. 2014;4(3):222-6doi: 10.1016/j.molmet.2014.12.007.
Haeusler, R. A., Camastra, S., Astiarraga, B., Nannipieri, M., Anselmino, M., & Ferrannini, E. (2015). Decreased expression of hepatic glucokinase in type 2 diabetes. Molecular metabolism, 4(3), 222-6. https://doi.org/10.1016/j.molmet.2014.12.007
Haeusler, Rebecca A, et al. "Decreased expression of hepatic glucokinase in type 2 diabetes." Molecular metabolism vol. 4,3 (2015): 222-6. doi: https://doi.org/10.1016/j.molmet.2014.12.007
Haeusler RA, Camastra S, Astiarraga B, Nannipieri M, Anselmino M, Ferrannini E. Decreased expression of hepatic glucokinase in type 2 diabetes. Mol Metab. 2014 Dec 18;4(3):222-6. doi: 10.1016/j.molmet.2014.12.007. eCollection 2015 Mar. PMID: 25737948; PMCID: PMC4338311.
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Mol Metab. 2014 Dec 18;4(3):222-6. doi: 10.1016/j.molmet.2014.12.007. eCollection 2015 Mar.

Decreased expression of hepatic glucokinase in type 2 diabetes.

Molecular metabolism

Rebecca A Haeusler, Stefania Camastra, Brenno Astiarraga, Monica Nannipieri, Marco Anselmino, Ele Ferrannini

Affiliations

  1. Columbia University, Department of Pathology and Cell Biology, New York, NY, USA.
  2. Department of Clinical and Experimental Medicine, University of Pisa School of Medicine, Pisa, Italy.
  3. Division of Bariatric Surgery, Santa Chiara Hospital, Pisa, Italy.
  4. Department of Clinical and Experimental Medicine, University of Pisa School of Medicine, Pisa, Italy ; CNR Institute of Clinical Physiology, Italy.

PMID: 25737948 PMCID: PMC4338311 DOI: 10.1016/j.molmet.2014.12.007

Abstract

BACKGROUND/OBJECTIVES: Increased endogenous glucose production is a hallmark of type 2 diabetes. Evidence from animal models has suggested that a likely cause of this is increased mRNA expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase (encoded by G6PC, PCK1 and PCK2). But another contributing factor may be decreased liver glucokinase (encoded by GCK).

METHODS: We examined expression of these enzymes in liver biopsies from 12 nondiabetic and 28 diabetic individuals. Diabetic patients were further separated into those with HbA1c lower or higher than 7.0.

RESULTS: In diabetic subjects with HbA1c > 7.0, we found that gluconeogenic enzymes were expressed normally, but GCK was suppressed more than 60%. Moreover, HbA1c and fasting glucose were negatively correlated with GCK, but showed no correlation with G6PC, PCK1, or PCK2.

CONCLUSION: These findings suggest an underlying dysregulation of hepatic GCK expression during frank diabetes, which has implications for the therapeutic use of glucokinase activators in this population.

Keywords: Diabetes; Glucokinase; Humans

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