Cloning and comparative bioinformatic analysis of feline glucose-6-phosphatase catalytic subunit cDNA

Lindbloom, Sara; LeCluyse, Michelle; Schermerhorn, Thomas

doi:10.1080/10425170701574920

Cited by 10 publications

(11 citation statements)

References 21 publications

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“…Percent (%) nucleotide identity is highest with pancreatic GK cDNAs from primates (>90%) and slightly less with rodent pancreatic GK cDNAs. The latter finding is consistent with a trend observed in other feline genes involved in carbohydrate metabolism, such as G6PC (glucose-6-phosphatase catalytic subunit) [13] and KHK (ketohexokinase) [14], which have shown greater nucleotide identity with primate and canine sequences than with rodent species. The ten putative exons identified in feline GK have homology with established exon sequences of human pancreatic GK.…”

Section: Discussionsupporting

confidence: 88%

Cloning and characterization of feline islet glucokinase

et al. 2014

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BackgroundGlucokinase (GK) is a metabolic enzyme encoded by the GCK gene and expressed in glucose-sensitive tissues, principally pancreatic islets cell and hepatocytes. The GK protein acts in pancreatic islets as a “glucose sensor” that couples fluctuations in the blood glucose concentration to changes in cellular function and insulin secretion. GCK and GK have proposed importance in the development and progression of diabetes mellitus and are potential therapeutic targets for diabetes treatment. The study was undertaken to determine the nucleotide sequence of feline pancreatic GK cDNA, predict the amino acid sequence and structure of the feline GK protein, and perform comparative bioinformatic analysis of feline cDNA and protein. Routine PCR techniques were used with cDNA from feline pancreas. Clones were assembled to obtain the full length cDNA. Protein prediction and modeling were performed using bioinformatic tools.ResultsFull-length feline pancreatic GK cDNA contains a 1398 nucleotide coding sequence with high identity to other pancreatic GK cDNAs. The deduced 465 amino acid feline protein has 15 amino acid substitutions not found in other mammalian GK proteins but maintains high structural homology with human GK. Feline pancreatic GK is highly conserved at nucleotide and protein levels. Residues crucial for substrate binding and catalysis are completely conserved in the feline protein.ConclusionMolecular analysis predicts that feline pancreatic GK functions similarly to other mammalian GK proteins.

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Section: Discussionsupporting

confidence: 88%

Cloning and characterization of feline islet glucokinase

et al. 2014

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“…Consistent with the need for a high gluconeogenic capacity, the activity of the glucose-6-phosphatase (G6Pase) enzyme system is comparatively high in feline liver compared to canine liver (Washizu et al 1999;Tanaka et al 2005). Molecular analysis of feline G6Pase indicates it is highly conserved at the level of mRNA and protein, suggesting that the high G6Pase activity that characterizes feline hepatic metabolism results from changes in gene expression rather than species-specific regulation of the G6Pase enzyme (Lindbloom et al 2008). Likewise, species-specific differences in hepatic gene expression may explain the comparatively low capacity for glucose phorphorylation previously observed in feline liver.…”

Section: Introductionmentioning

confidence: 76%

Lack of glucokinase regulatory protein expression may contribute to low glucokinase activity in feline liver

et al. 2008

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In most mammals, glucokinase (GK) acts as a hepatic "glucose sensor" that permits hepatic metabolism to respond appropriately to changes in plasma glucose concentrations. GK activity is potently regulated by the glucokinase regulatory protein (GKRP), which is encoded by the GCKR gene. GKRP binds GK in the nucleus and inhibits its activity. GK becomes active when it is released from GKRP and translocates to the cytosol. Low glucokinase (GK) activity is reported to be a principal feature of feline hepatic carbohydrate metabolism but the molecular pathways that regulate GK activity are not known. This study examined the hypothesis that species-specific differences in GKRP expression parallel the low GK activity observed in feline liver. Hepatic GKRP expression was examined using RT-PCR, immunoblot, and confocal immunomicroscopy. The results show that the GCKR gene is present in the feline genome but GCKR mRNA and the GKRP protein were absent in feline liver. The lack of GKRP expression in feline liver indicates that the low GK activity cannot be the result of GKRP-mediated inhibition of the GK enzyme. However, the absence of the permissive effects of GCKR expression on GK expression and activity may contribute to reduced GK enzyme activity in feline liver. The study results show that the cat is a natural model for GCKR knockout and may be useful to study regulation of GCKR expression and its role in hepatic glucose-sensing and carbohydrate metabolism.

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“…Although feline genes involved in glucose metabolism appear to be highly conserved (79–81), work in cats has clearly demonstrated that the molecular basis of feline hepatic glucose-sensing differs from the model defined in the non-carnivore liver (82). GCK and GCKR (the gene that encodes GKRP) mRNAs are absent from feline liver and activities of GCK and GKRP proteins are not detectable (35, 38, 82).…”

Section: Carnivore Hepatic Glucose-sensing Pathwaysmentioning

confidence: 99%

Normal Glucose Metabolism in Carnivores Overlaps with Diabetes Pathology in Non-Carnivores

Schermerhorn

2013

Front. Endocrinol.

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Carnivores, such as the dolphin and the domestic cat, have numerous adaptations that befit consumption of diets with high protein and fat content, with little carbohydrate content. Consequently, nutrient metabolism in carnivorous species differs substantially from that of non-carnivores. Important metabolic pathways known to differ between carnivores and non-carnivores are implicated in the development of diabetes and insulin resistance in non-carnivores: (1) the hepatic glucokinase (GCK) pathway is absent in healthy carnivores yet GCK deficiency may result in diabetes in rodents and humans, (2) healthy dolphins and cats are prone to periods of fasting hyperglycemia and exhibit insulin resistance, both of which are risk factors for diabetes in non-carnivores. Similarly, carnivores develop naturally occurring diseases such as hemochromatosis, fatty liver, obesity, and diabetes that have strong parallels with the same disorders in humans. Understanding how evolution, environment, diet, and domestication may play a role with nutrient metabolism in the dolphin and cat may also be relevant to human diabetes.

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Cloning and comparative bioinformatic analysis of feline glucose-6-phosphatase catalytic subunit cDNA

Cited by 10 publications

References 21 publications

Cloning and characterization of feline islet glucokinase

Cloning and characterization of feline islet glucokinase

Lack of glucokinase regulatory protein expression may contribute to low glucokinase activity in feline liver

Normal Glucose Metabolism in Carnivores Overlaps with Diabetes Pathology in Non-Carnivores

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