Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids

ABSTRACT: Hepatic gluconeogenesis from amino acids contributes significantly to diabetic hyperglycemia, but the molecular mechanisms involved are incompletely understood. Alanine transaminases (ALT1 and ALT2) catalyze the interconversion of alanine and pyruvate, which is required for gluconeogenesis from alanine. Hepatocyte-specific knockout of Gpt2 attenuated incorporation of 13C-alanine into newly synthesized glucose by hepatocytes. However, Gpt2 knockout in liver had no effect on glucose concentrations in lean mice, which may suggest that metabolic compensation is occurring.

ORGANISM(S): Mus musculus

PROVIDER: GSE199975 | GEO | 2022/04/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids

Project description:Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids

| PRJNA822390 | ENA

Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids.

Project description: Not available

| S-EPMC9121396 | biostudies-literature

Dysfunction of the circadian clock in the renal tubule leads to enhanced renal gluconeogenesis and exacerbated hyperglycemia in diabetes

Project description:In diabetes, the kidney contributes to the development of diabetic hyperglycemia by increasing glucose reabsorption from the primary urine and by upregulating gluconeogenesis in the proximal tubule. However, these two processes are also controlled by the circadian clock, a mechanism that synchronizes a large number of specific renal functions with environmental daily cycles. Here, we investigated the (patho)physiological role of intrinsic renal tubule circadian clocks in the diabetic kidney. We demonstrate that diabetic mice devoid of the circadian transcriptional regulator BMAL1 in the renal tubule exhibit additional enhancement of renal gluconeogenesis, exacerbated hyperglycemia, increased glucosuria, polyuria and renal hypertrophy. Collectively, our results suggest that diabetic hyperglycemia can be worsened by dysfunction or misalignment of intrinsic renal circadian clocks.

2022-05-27 | GSE178319 | GEO

Transcriptional response of Corynebacterium glutamicum C1 to 3 mM indole-alanine dipeptide

Project description:Differential gene expression analysis of C. glutamicum C1 in presence of 3 mM indole-alanine dipeptide compared to control conditions without indole-alanine dipeptide. C. glutamicum C1 cells were cultivated in CGXII minimal medium with 40 g per litre glucose in presence or absence of 3 mM indole-alanine dipeptide and harvested during exponential phase (o.d.600 6).

2020-12-31 | GSE159888 | GEO

Endogenous renal adiponectin drives gluconeogenesis through enhancing pyruvate and fatty acid utilization

Project description:Adiponectin is an important secretory protein, primarily produced in adipose tissue. However, low but detectable expression of adiponectin can be observed in cell types beyond adipocytes, particularly in kidney tubular cells, but its local renal role is unknown. We assessed the role of renal adiponectin by utilizing male doxycycline inducible kidney tubular cell-specific adiponectin overexpression or knockout mice. Kidney-specific adiponectin overexpression induces a doubling of phosphoenolpyruvate carboxylase expression and enhanced pyruvate-mediated glucose production, tricarboxylic acid cycle intermediates and an upregulation of fatty acid oxidation (FAO). The inhibition of FAO reduces the adiponectin-induced enhancement of glucose production, highlighting the role of FAO in the induction of renal gluconeogenesis. In contrast, kidney-specific adiponectin deleted mice exhibit enhanced glucose tolerance as well as a lower utilization and greater accumulation of lipid species. In summary, renal adiponectin is a potent inducer of gluconeogenesis by driving enhanced FAO in the kidney and underline the important systemic role of renal gluconeogenesis.

2023-09-20 | GSE242095 | GEO

SHP-1 regulates transcription of PCK1 to control gluconeogenesis

Project description:The protein-tyrosine phosphatase SHP-1 (PTPN6) is an important glucose homeostasis modulator. Besides negatively regulating insulin signaling, the specific role of SHP-1 in metabolic control remains poorly understood. We show that SHP-1 acts as a co-activator for transcription of the phosphoenolpyruvate carboxykinase 1 (PCK1) gene, thereby modulating basal gluconeogenesis in hepatocytes. SHP-1 interacts with RNA polymerase II-subunits and signal transducer and activator of transcription 5 (STAT5), and localizes to the nucleus, where a sub-fraction of SHP-1 associates with chromatin. While SHP-1 binds to the PCK1-promoter, its loss affects RNA polymerase II-recruitment to this and other promoters of genes enriched for glucose metabolism-related functions. SHP-1-downregulation, and similarly STAT5 pharmacological inhibition reduce PCK1-transcript levels correlating with blunted gluconeogenesis. Overall, we identified a novel molecular SHP-1-function, that of a regulator of PCK1-transcription and subsequently hepatic gluconeogenesis, through physical interaction with the transcription machinery, mediated by an Akt-independent mechanism, but independent of STAT5 tyrosine-phosphorylation status.

2023-09-08 | GSE174142 | GEO

Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids

Project description:Acetate, propionate and butyrate are the main short-chain fatty acids (SCFAs) that arise from the fermentation of fibers by the colonic microbiota. While many studies focus on the regulatory role of SCFAs, their quantitative role as a catabolic or anabolic substrate for the host has received relatively little attention. To investigate this aspect, we infused conscious mice with physiological quantities of stable isotopes [1-13C]acetate, [2-13C]propionate or [2,4-13C2]butyrate directly into the cecum, which is the natural production site in mice, and analyzed their interconversion by the microbiota as well as their metabolism by the host. Cecal interconversion - pointing to microbial cross-feeding - was high between acetate and butyrate, low between butyrate and propionate and almost absent between acetate and propionate. As much as 62% of infused propionate was used in whole-body glucose production, in line with its role as gluconeogenic substrate. Conversely, glucose synthesis from propionate accounted for 69% of total glucose production. The synthesis of palmitate and cholesterol in the liver was high from cecal acetate (2.8% and 0.7%, respectively) and butyrate (2.7% and 0.9%, respectively) as substrates, but low or absent from propionate (0.6% and 0.0%, respectively). Label incorporation due to chain elongation of stearate was approximately 8-fold higher than de novo synthesis of stearate. Microarray data suggested that SCFAs exert only a mild regulatory effect on the expression of genes involved in hepatic metabolic pathways during the 6h infusion period. Altogether, gut-derived acetate, propionate and butyrate play important roles as substrates for glucose, cholesterol and lipid metabolism. Mice were infused in cecum with stably-labelled isotopes of the three main short chain fatty acids or control solution. After 6 hrs, livers were removed and pooled RNA samples were subjected to gene expression profiling.

2013-10-21 | E-GEOD-45926 | biostudies-arrayexpress

TOX3 drives hepatic gluconeogenesis and hyperglycemia by targeting FoxO1 [ChIP-seq]

Project description:Purpose: The goals of this study are to explore role of Tox3 in glucose homeostasis Methods: Tox3-activation was generated by adenovirus from Genechem.Successful activation of Tox3 was determined by mRNA and protein expression.

2024-01-22 | GSE228791 | GEO

TOX3 drives hepatic gluconeogenesis and hyperglycemia by targeting FoxO1 [RNA-seq]

2024-01-22 | GSE228790 | GEO

Loss of TSC complex enhances gluconeogenesis via upregulation of Dlk1-Dio3 locus miRNAs

Project description:Loss of the tumor suppressor tuberous sclerosis complex 1 (Tsc1) in the liver promotes gluconeogenesis and glucose intolerance. We asked whether this could be attributed to aberrant expression of small RNAs. We preformed small-RNA sequencing on liver of Tsc1 knock-out mice, and found that miRNAs of the delta like homolog 1 (Dlk1) – deiodinase iodothyronine type III (Dio3) locus are upregulated in an mTORC1-dependent manner. Sustained mTORC1 signaling during development prevented CpG methylation and silencing of the Dlk1-Dio3 locus, thereby increasing miRNA transcription. Deletion of miRNAs encoded by the Dlk1-Dio3 locus reduced gluconeogenesis, glucose intolerance and fasting blood glucose levels. Thus, miRNAs contribute to the metabolic effects observed upon loss of TSC1 and hyperactivation of mTORC1 in the liver. Furthermore, we show that miRNA is a downstream effector of hyperactive mTORC1 signaling.

2019-12-04 | GSE141361 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data