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Gene expression profile analysis of type 2 diabetic mouse liver.

Zhang F, Xu X, Zhang Y, Zhou B, He Z, Zhai Q - PLoS ONE (2013)

Bottom Line: Analysis of the key enzyme genes in fatty acid and glucose metabolism showed that some key enzyme genes were significantly increased and none of the detected key enzyme genes were decreased.In addition, FunDo analysis showed that liver cancer and hepatitis were most likely to be associated with diabetes.Taken together, this study provides the digital gene expression profile of diabetic mouse liver, and demonstrates the main diabetes-associated hepatic biological processes, pathways, key enzyme genes in fatty acid and glucose metabolism and potential hepatic diseases.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

ABSTRACT
Liver plays a key role in glucose metabolism and homeostasis, and impaired hepatic glucose metabolism contributes to the development of type 2 diabetes. However, the precise gene expression profile of diabetic liver and its association with diabetes and related diseases are yet to be further elucidated. In this study, we detected the gene expression profile by high-throughput sequencing in 9-week-old normal and type 2 diabetic db/db mouse liver. Totally 12132 genes were detected, and 2627 genes were significantly changed in diabetic mouse liver. Biological process analysis showed that the upregulated genes in diabetic mouse liver were mainly enriched in metabolic processes. Surprisingly, the downregulated genes in diabetic mouse liver were mainly enriched in immune-related processes, although all the altered genes were still mainly enriched in metabolic processes. Similarly, KEGG pathway analysis showed that metabolic pathways were the major pathways altered in diabetic mouse liver, and downregulated genes were enriched in immune and cancer pathways. Analysis of the key enzyme genes in fatty acid and glucose metabolism showed that some key enzyme genes were significantly increased and none of the detected key enzyme genes were decreased. In addition, FunDo analysis showed that liver cancer and hepatitis were most likely to be associated with diabetes. Taken together, this study provides the digital gene expression profile of diabetic mouse liver, and demonstrates the main diabetes-associated hepatic biological processes, pathways, key enzyme genes in fatty acid and glucose metabolism and potential hepatic diseases.

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The expression of enzymes directly participated in gluconeogenesis, glycolysis and glycogen metabolism was increased or not significantly changed in diabetic mouse liver.(A, D) Schematic of gluconeogenesis, glycolysis and glycogen metabolism, and the expression of enzymes directly participated in these processes of diabetic mouse liver. The key enzymes include HK, PFK-1 and PK for glycolysis, G6Pase, FBPase and PEPCK for gluconeogenesis, HK, UDP-GP and GS for glycogen synthesis, and GP for glycogenolysis. Red color represents the upregulated genes in diabetic mouse liver with fold change ≥ 1.5 and FDR < 0.001, gray color indicates no significant change, and white color indicates the genes were not detected. (B, C and E) The mRNA levels of the enzymes directly participated in glycolysis, gluconeogenesis and glycogen metabolism in normal (N) and diabetic (DB) mouse liver. HK, hexokinase; PGI, Phosphoglucoisomerase; PFK-1, phosphofructokinase; ALDB, aldolase; TPI, triose phosphate isomerase; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; PGK, phosphoglycerokinase; PGM, phosphoglyceromutase; PK, pyruvate kinase; LDH, lactate dehydrogenase; PDH, pyruvate dehydrogenase; PC, pyruvate carboxylase; G6Pase, Glucose-6-Phosphatase; FBPase, Fructose 1,6-bisphosphatase; PEPCK, Phosphoenolpyruvate carboxykinase; UDP-GP, Uridine diphosphoglucose pyrophosphorylase; GS, Glycogen Synthase; GP, Glycogen Phosphorylase.
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pone-0057766-g004: The expression of enzymes directly participated in gluconeogenesis, glycolysis and glycogen metabolism was increased or not significantly changed in diabetic mouse liver.(A, D) Schematic of gluconeogenesis, glycolysis and glycogen metabolism, and the expression of enzymes directly participated in these processes of diabetic mouse liver. The key enzymes include HK, PFK-1 and PK for glycolysis, G6Pase, FBPase and PEPCK for gluconeogenesis, HK, UDP-GP and GS for glycogen synthesis, and GP for glycogenolysis. Red color represents the upregulated genes in diabetic mouse liver with fold change ≥ 1.5 and FDR < 0.001, gray color indicates no significant change, and white color indicates the genes were not detected. (B, C and E) The mRNA levels of the enzymes directly participated in glycolysis, gluconeogenesis and glycogen metabolism in normal (N) and diabetic (DB) mouse liver. HK, hexokinase; PGI, Phosphoglucoisomerase; PFK-1, phosphofructokinase; ALDB, aldolase; TPI, triose phosphate isomerase; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; PGK, phosphoglycerokinase; PGM, phosphoglyceromutase; PK, pyruvate kinase; LDH, lactate dehydrogenase; PDH, pyruvate dehydrogenase; PC, pyruvate carboxylase; G6Pase, Glucose-6-Phosphatase; FBPase, Fructose 1,6-bisphosphatase; PEPCK, Phosphoenolpyruvate carboxykinase; UDP-GP, Uridine diphosphoglucose pyrophosphorylase; GS, Glycogen Synthase; GP, Glycogen Phosphorylase.

Mentions: Diabetes is featured with impaired glucose metabolism [4], [5], so we also analyzed the transcriptional level of enzyme genes participated in glucose metabolism. Schematic of four major hepatic glucose metabolism subprocesses including glycolysis, gluconeogenesis, glycogen synthesis and glycogenolysis were shown in Figure 4A and 4D. Surprisingly, none of these detected enzyme genes was downregulated in diabetic mouse liver, and numerous enzyme genes in glycolysis, gluconeogenesis and glycogenolysis were significantly upregulated (Figure 4A–E). For example, Pklr, encoding the rate-limiting enzymes pyruvate kinase (PK) in glycolysis [24], was upregulated to 2.66-fold. Meanwhile, both Fbp1 and Pck1, encoding the rate-limiting enzymes FBPase and phosphoenolpyruvate carboxykinase (PEPCK) in gluconeogenesis pathway were upregulated to 3.09- and 3.06-fold respectively. The role of glycogen metabolism is to maintain blood-glucose levels through glycogenesis and glycogenolysis [25]. We found that Pygl, encoding the rate-limiting enzyme glycogen phosphorylase in glycogenolysis, was significantly upregulated to 1.49-fold (Figure 4D,E). These results suggest that glycolysis, gluconeogenesis and glycogenolysis are enhanced in 9-week-old diabetic db/db mouse liver.


Gene expression profile analysis of type 2 diabetic mouse liver.

Zhang F, Xu X, Zhang Y, Zhou B, He Z, Zhai Q - PLoS ONE (2013)

The expression of enzymes directly participated in gluconeogenesis, glycolysis and glycogen metabolism was increased or not significantly changed in diabetic mouse liver.(A, D) Schematic of gluconeogenesis, glycolysis and glycogen metabolism, and the expression of enzymes directly participated in these processes of diabetic mouse liver. The key enzymes include HK, PFK-1 and PK for glycolysis, G6Pase, FBPase and PEPCK for gluconeogenesis, HK, UDP-GP and GS for glycogen synthesis, and GP for glycogenolysis. Red color represents the upregulated genes in diabetic mouse liver with fold change ≥ 1.5 and FDR < 0.001, gray color indicates no significant change, and white color indicates the genes were not detected. (B, C and E) The mRNA levels of the enzymes directly participated in glycolysis, gluconeogenesis and glycogen metabolism in normal (N) and diabetic (DB) mouse liver. HK, hexokinase; PGI, Phosphoglucoisomerase; PFK-1, phosphofructokinase; ALDB, aldolase; TPI, triose phosphate isomerase; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; PGK, phosphoglycerokinase; PGM, phosphoglyceromutase; PK, pyruvate kinase; LDH, lactate dehydrogenase; PDH, pyruvate dehydrogenase; PC, pyruvate carboxylase; G6Pase, Glucose-6-Phosphatase; FBPase, Fructose 1,6-bisphosphatase; PEPCK, Phosphoenolpyruvate carboxykinase; UDP-GP, Uridine diphosphoglucose pyrophosphorylase; GS, Glycogen Synthase; GP, Glycogen Phosphorylase.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585940&req=5

pone-0057766-g004: The expression of enzymes directly participated in gluconeogenesis, glycolysis and glycogen metabolism was increased or not significantly changed in diabetic mouse liver.(A, D) Schematic of gluconeogenesis, glycolysis and glycogen metabolism, and the expression of enzymes directly participated in these processes of diabetic mouse liver. The key enzymes include HK, PFK-1 and PK for glycolysis, G6Pase, FBPase and PEPCK for gluconeogenesis, HK, UDP-GP and GS for glycogen synthesis, and GP for glycogenolysis. Red color represents the upregulated genes in diabetic mouse liver with fold change ≥ 1.5 and FDR < 0.001, gray color indicates no significant change, and white color indicates the genes were not detected. (B, C and E) The mRNA levels of the enzymes directly participated in glycolysis, gluconeogenesis and glycogen metabolism in normal (N) and diabetic (DB) mouse liver. HK, hexokinase; PGI, Phosphoglucoisomerase; PFK-1, phosphofructokinase; ALDB, aldolase; TPI, triose phosphate isomerase; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; PGK, phosphoglycerokinase; PGM, phosphoglyceromutase; PK, pyruvate kinase; LDH, lactate dehydrogenase; PDH, pyruvate dehydrogenase; PC, pyruvate carboxylase; G6Pase, Glucose-6-Phosphatase; FBPase, Fructose 1,6-bisphosphatase; PEPCK, Phosphoenolpyruvate carboxykinase; UDP-GP, Uridine diphosphoglucose pyrophosphorylase; GS, Glycogen Synthase; GP, Glycogen Phosphorylase.
Mentions: Diabetes is featured with impaired glucose metabolism [4], [5], so we also analyzed the transcriptional level of enzyme genes participated in glucose metabolism. Schematic of four major hepatic glucose metabolism subprocesses including glycolysis, gluconeogenesis, glycogen synthesis and glycogenolysis were shown in Figure 4A and 4D. Surprisingly, none of these detected enzyme genes was downregulated in diabetic mouse liver, and numerous enzyme genes in glycolysis, gluconeogenesis and glycogenolysis were significantly upregulated (Figure 4A–E). For example, Pklr, encoding the rate-limiting enzymes pyruvate kinase (PK) in glycolysis [24], was upregulated to 2.66-fold. Meanwhile, both Fbp1 and Pck1, encoding the rate-limiting enzymes FBPase and phosphoenolpyruvate carboxykinase (PEPCK) in gluconeogenesis pathway were upregulated to 3.09- and 3.06-fold respectively. The role of glycogen metabolism is to maintain blood-glucose levels through glycogenesis and glycogenolysis [25]. We found that Pygl, encoding the rate-limiting enzyme glycogen phosphorylase in glycogenolysis, was significantly upregulated to 1.49-fold (Figure 4D,E). These results suggest that glycolysis, gluconeogenesis and glycogenolysis are enhanced in 9-week-old diabetic db/db mouse liver.

Bottom Line: Analysis of the key enzyme genes in fatty acid and glucose metabolism showed that some key enzyme genes were significantly increased and none of the detected key enzyme genes were decreased.In addition, FunDo analysis showed that liver cancer and hepatitis were most likely to be associated with diabetes.Taken together, this study provides the digital gene expression profile of diabetic mouse liver, and demonstrates the main diabetes-associated hepatic biological processes, pathways, key enzyme genes in fatty acid and glucose metabolism and potential hepatic diseases.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

ABSTRACT
Liver plays a key role in glucose metabolism and homeostasis, and impaired hepatic glucose metabolism contributes to the development of type 2 diabetes. However, the precise gene expression profile of diabetic liver and its association with diabetes and related diseases are yet to be further elucidated. In this study, we detected the gene expression profile by high-throughput sequencing in 9-week-old normal and type 2 diabetic db/db mouse liver. Totally 12132 genes were detected, and 2627 genes were significantly changed in diabetic mouse liver. Biological process analysis showed that the upregulated genes in diabetic mouse liver were mainly enriched in metabolic processes. Surprisingly, the downregulated genes in diabetic mouse liver were mainly enriched in immune-related processes, although all the altered genes were still mainly enriched in metabolic processes. Similarly, KEGG pathway analysis showed that metabolic pathways were the major pathways altered in diabetic mouse liver, and downregulated genes were enriched in immune and cancer pathways. Analysis of the key enzyme genes in fatty acid and glucose metabolism showed that some key enzyme genes were significantly increased and none of the detected key enzyme genes were decreased. In addition, FunDo analysis showed that liver cancer and hepatitis were most likely to be associated with diabetes. Taken together, this study provides the digital gene expression profile of diabetic mouse liver, and demonstrates the main diabetes-associated hepatic biological processes, pathways, key enzyme genes in fatty acid and glucose metabolism and potential hepatic diseases.

Show MeSH
Related in: MedlinePlus