Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0011860 (
type 2 diabetes
)
57,723
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Genome-wide association studies (GWAS) have linked
IGF2BP2
single-nucleotide polymorphisms (SNPs) with
type 2 diabetes
(T2D). Mice overexpressing
mIGF2BP2
have elevated cholesterol levels when fed a diet that induces hepatic steatosis. These and other studies suggest an important role for insulin growth factor 2 mRNA binding protein 2 (IGF2BP2) in the initiation and progression of several metabolic disorders. The ATPase binding cassette protein
ABCA1
initiates nascent high-density apolipoprotein (HDL) biogenesis by transferring phospholipid and cholesterol to delipidated apolipoprotein AI (ApoAI). Individuals with mutational ablation of
ABCA1
have Tangier disease, which is characterized by a complete loss of HDL. MicroRNA 33a and 33b (miR-33a/b) bind to the 3' untranslated region (UTR) of
ABCA1
and repress its posttranscriptional gene expression. Here, we show that IGF2BP2 works together with miR-33a/b in repressing
ABCA1
expression. Our data suggest that IGF2BP2 is an accessory protein of the argonaute (AGO2)-miR-33a/b-RISC complex, as it directly binds to miR-33a/b, AGO2, and the 3' UTR of
ABCA1
Finally, we show that mice overexpressing human
IGF2BP2
have decreased
ABCA1
expression, increased low-density lipoprotein-cholesterol (LDL-C) and cholesterol blood levels, and elevated SREBP-dependent signaling. Our data support the hypothesis that IGF2BP2 has an important role in maintaining lipid homeostasis through its modulation of
ABCA1
expression, as its overexpression or loss leads to dyslipidemia.
...
PMID:Human Insulin Growth Factor 2 mRNA Binding Protein 2 Increases MicroRNA 33a/b Inhibition of Liver
ABCA1
Expression and Alters Low-Density Apolipoprotein Levels in Mice. 3248 98
Statin is the medication most widely prescribed to reduce plasma cholesterol levels. Yet, how the medication contributes to diabetes risk and impaired glucose metabolism is not clear. This study aims to examine the epigenetic mechanisms of
ABCG1
through which statin use associates with risk of
type 2 diabetes
. We determined the association between the statin use, DNA methylation at
ABCG1
and
type 2 diabetes
/glycemic traits in the Framingham Heart Study Offspring (FHS,
n
= 2741), with validation in the Women's Health Initiative Study (WHI,
n
= 2020). The causal effect of statin use on the risk of
type 2 diabetes
was examined using a two-step Mendelian randomization approach. Next, based on transcriptome analysis, we determined the links between the medication-associated epigenetic status of
ABCG1
and biological pathways on the pathogenesis of
type 2 diabetes
. Our results showed that DNA methylation levels at cg06500161 of
ABCG1
were positively associated with the use of statin,
type 2 diabetes
and related traits (fasting glucose and insulin) in FHS and WHI. Two-step Mendelian randomization suggested a causal effect of statin use on
type 2 diabetes
and related traits through epigenetic mechanisms, specifically, DNA methylation at cg06500161. Our results highlighted that gene expression of
ABCG1,
ABCA1
and
ACSL3
, involved in both cholesterol metabolism and glycemic pathways, was inversely associated with statin use, CpG methylation, and diabetic signatures. We concluded that DNA methylation site cg06500161 at
ABCG1
is a mediator of the association between statins and risk of
type 2 diabetes
.
...
PMID:Statin Use Associates With Risk of Type 2 Diabetes via Epigenetic Patterns at
ABCG1
. 3261 41
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