Name	Type 2 diabetes mellitus
ICD	ICD-11: 5A11

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acetyl-CoA carboxylase 1 (ACC1/ACACA), Acly, Dgat2, Ehhadh, Fasn, Foxo, Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3 fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were used for experiments.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, ATP-citrate synthase (ACLY), Dgat2, Ehhadh, Fasn, Foxo, Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3 fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were used for experiments.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Diacylglycerol O-acyltransferase 2 (DGAT2), Ehhadh, Fasn, Foxo, Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3 fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were used for experiments.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (FASN), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Ehhadh, Fasn, Foxo, Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3 fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were used for experiments.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Ehhadh, Fasn, Forkhead box protein O1 (FOXO1), Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3 fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were used for experiments.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Ehhadh, Fasn, Foxo, Pgc1a and NAD-dependent protein deacetylase sirtuin-1 (SIRT1), which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3 fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were used for experiments.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	In T2D, IMP2 directly binds to In Pancreas/duodenum homeobox protein 1 (Pdx1) mRNA and stimulates its translation in an m6A dependent manner.
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	EndoC-betaH1	Normal	Homo sapiens	CVCL_L909

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Peroxisomal bifunctional enzyme (EHHADH), Fasn, Foxo, Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3 fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were used for experiments.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Ehhadh, Fasn, Foxo, PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A) and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3 fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were used for experiments.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	FTO knockdown elevated Transgelin (SM22alpha) expression and m6A-binding protein IGF2BP2 enhanced SM22alpha mRNA stability by recognizing and binding to m6A methylation modified mRNA. m6A methylation-mediated elevation of SM22alpha restrained VSMC proliferation and migration and ameliorated intimal hyperplasia in T2DM.
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	VSMC (Human aortic vascular smooth muscle cells)

Ref 1	METTL3 inhibits hepatic insulin sensitivity via N6-methyladenosine modification of Fasn mRNA and promoting fatty acid metabolism. Biochem Biophys Res Commun. 2019 Oct 8;518(1):120-126. doi: 10.1016/j.bbrc.2019.08.018. Epub 2019 Aug 10.
Ref 2	RNA m6A reader IMP2/IGF2BP2 promotes pancreatic Beta-cell proliferation and insulin secretion by enhancing PDX1 expression. Mol Metab. 2021 Jun;48:101209. doi: 10.1016/j.molmet.2021.101209. Epub 2021 Mar 9.
Ref 3	M(6)A methylation-mediated elevation of SM22Alpha?inhibits the proliferation and migration of?vascular smooth muscle cells and ameliorates?intimal hyperplasia in type 2 diabetes mellitus. Biol Chem. 2021 Dec 7;403(3):317-329. doi: 10.1515/hsz-2021-0296. Print 2022 Feb 23.