Publications by authors named "K Kalemba"

Fasting hyperglycemia in diabetes mellitus is caused by unregulated glucagon secretion that activates gluconeogenesis (GNG) and increases the use of pyruvate, lactate, amino acids, and glycerol. Studies of GNG in hepatocytes, however, tend to test a limited number of substrates at nonphysiologic concentrations. Therefore, we treated cultured primary hepatocytes with three identical substrate mixtures of pyruvate/lactate, glutamine, and glycerol at serum fasting concentrations, where a different U-C- or 2-C-labeled substrate was substituted in each mix.

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Article Synopsis
  • Nonalcoholic fatty liver disease (NAFLD) is a growing global health issue linked to obesity and metabolic disorders, characterized by excessive fat buildup in the liver that can lead to more severe conditions like NASH and cirrhosis.
  • Current treatments for NAFLD are lacking, but recent research indicates that activating the kisspeptin 1 receptor (KISS1R) could provide therapeutic benefits by regulating fat metabolism.
  • Studies in mice demonstrate that stimulation of KISS1R reduces fat accumulation in the liver and could protect against the progression of NAFLD, highlighting its potential as a new target for treatment.
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The liver is among the principal organs for glucose homeostasis and metabolism. Studies of liver metabolism are limited by the inability to expand primary hepatocytes in vitro while maintaining their metabolic functions. Human hepatic three-dimensional (3D) organoids have been established using defined factors, yet hepatic organoids from adult donors showed impaired expansion.

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Gluconeogenesis (GNG) is production of glucose from endogenous carbon sources. Although it is a commonly studied pathway, particularly in disease, there is a lack of consensus about substrate preference. Moreover, primary hepatocytes are the current gold standard for liver studies, but no direct comparison of substrate preference at physiological fasting concentrations has been performed.

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Glucose and glycerol are important circulating metabolites. Due to poor ionization and/or ion suppression, the liquid chromatography-mass spectrometry (LC-MS) detection of glucose and glycerol presents challenges. Here, we propose an efficient LC-MS method of quantitative glucose and glycerol detection via enzymatic derivatization to glucose-6-phosphate and sn-glycerol-3-phosphate, respectively.

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