Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Muscle Specific Insulin Receptor Overexpression Protects Mice from Diet-Induced Glucose Intolerance but Leads to Post-Receptor Insulin Resistance

ABSTRACT: Muscle Specific Insulin Receptor Overexpression Protects Mice from Diet-Induced Glucose Intolerance but Leads to Post-Receptor Insulin Resistance

PROVIDER: PRJNA629568 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR11657107_1.fastq.gz	Fastqsanger.gz
	SRR11657107_2.fastq.gz	Fastqsanger.gz
	SRR11657108_1.fastq.gz	Fastqsanger.gz
	SRR11657108_2.fastq.gz	Fastqsanger.gz
	SRR11657109_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 24

Similar Datasets

Muscle Specific Insulin Receptor Overexpression Protects Mice from Diet-Induced Glucose Intolerance but Leads to Post-Receptor Insulin Resistance

Project description:Skeletal muscle insulin resistance is a prominent early feature in the pathogenesis of type 2 diabetes (T2D). In attempt to overcome this defect, we generated mice overexpressing insulin receptors (IR) specifically in skeletal muscle (IRMOE). On normal chow, IRMOE mice have similar body weight as controls, but an increase in lean mass and glycolytic muscle fibers and reduced fat mass. IRMOE mice also show higher basal phosphorylation of IR, IRS-1 and Akt in muscle and improved glucose tolerance compared to controls. When challenged with high fat diet (HFD), IRMOE mice are protected from diet-induced obesity. This is associated with reduced inflammation in fat and liver, improved glucose tolerance and improved systemic insulin sensitivity. Surprisingly, however, in both chow and HFD-fed mice, insulin stimulated Akt phosphorylation is significantly reduced in muscle of IRMOE mice, indicating post-receptor insulin resistance. RNA sequencing reveals downregulation of several post-receptor signaling proteins that contribute to this resistance. Thus, enhancing early insulin signaling in muscle by overexpression of the insulin receptor protects mice from diet-induced obesity and its effects on glucose metabolism. However, chronic overstimulation of this pathway leads to post-receptor desensitization, indicating the critical balance between normal signaling and hyperstimulation of the insulin signaling pathway.

2020-09-01 | GSE149662 | GEO

Muscle-Specific Insulin Receptor Overexpression Protects Mice From Diet-Induced Glucose Intolerance but Leads to Postreceptor Insulin Resistance.

Project description:Skeletal muscle insulin resistance is a prominent early feature in the pathogenesis of type 2 diabetes. In attempt to overcome this defect, we generated mice overexpressing insulin receptors (IR) specifically in skeletal muscle (IRMOE). On normal chow, IRMOE mice have body weight similar to that of controls but an increase in lean mass and glycolytic muscle fibers and reduced fat mass. IRMOE mice also show higher basal phosphorylation of IR, IRS-1, and Akt in muscle and improved glucose tolerance compared with controls. When challenged with high-fat diet (HFD), IRMOE mice are protected from diet-induced obesity. This is associated with reduced inflammation in fat and liver, improved glucose tolerance, and improved systemic insulin sensitivity. Surprisingly, however, in both chow and HFD-fed mice, insulin-stimulated Akt phosphorylation is significantly reduced in muscle of IRMOE mice, indicating postreceptor insulin resistance. RNA sequencing reveals downregulation of several postreceptor signaling proteins that contribute to this resistance. Thus, enhancing early insulin signaling in muscle by overexpression of the IR protects mice from diet-induced obesity and its effects on glucose metabolism. However, chronic overstimulation of this pathway leads to postreceptor desensitization, indicating the critical balance between normal signaling and hyperstimulation of the insulin signaling pathway.

| S-EPMC7576573 | biostudies-literature

Genetic ablation of CD38 protects against Western diet-induced exercise intolerance and metabolic inflexibility

Project description:CD38, a multi-functional membrane receptor and enzyme, consumes NAD+ to generate products such as cyclic-ADP-ribose. CD38 knockout mice show elevated tissue and blood NAD+ level. Chronic feeding of high-fat, high-sucrose diet to wild type mice leads to exercise intolerance and reduced metabolic flexibility. Loss of CD38 by genetic mutation protects mice from diet-induced metabolic deficit. These animal model results suggest that elevation of tissue NAD+ through genetic ablation of CD38 can profoundly alter energy homeostasis in animals that are maintained on a calorically-excessive Western diet.

2015-05-20 | GSE69062 | GEO

Visceral adipocyte-derived extracellular vesicle miR-27a-5p elicits glucose intolerance by inhibiting pancreatic b-cell insulin secretion

Project description:Pancreatic β-cell dysfunction caused by obesity can be associated with alterations in the levels of microRNAs (miRNAs). However, the role of miRNAs in such processes remains elusive. Here, we show that pancreatic islet miR-27a-5p, which is markedly increased in obese mice and impairs insulin secretion, is mainly delivered by visceral adipocyte-derived extracellular vesicles (EVs). Depleting miR-27a-5p significantly improves insulin secretion and glucose intolerance in db/db mice. Supporting the function of EVs’ miR-27a-5p as a key pathogenic factor, intravenous injection of miR-27a-5p-containing EVs shows their distribution in mouse pancreatic islets. Tracing the injected AAV-miR-27a-5p (AAV-miR-27a) or AAV-FABP4-miR-27a-5p (AAV-FABP4-miR-27a) in visceral fat results in upregulating miR-27a-5p in EVs and serum, and elicits mouse pancreatic β-cell dysfunction. Mechanistically, miR-27a-5p directly targets L-type Ca2+ channel subtype CaV1.2 (Cacna1c) and reduces insulin secretion in β-cells. Overexpressing mouse CaV1.2 largely abolishes the insulin secretion injury induced by miR-27a-5p. These findings reveal a causative role of EVs’ miR-27a-5p in visceral adipocyte-mediated pancreatic β-cell dysfunction in obesity-associated type 2 diabetes mellitus.

2024-12-04 | GSE271706 | GEO

Transcription profiling of fat and normal adipocytes from insulin receptor knockout mice sorted into small and large cells

Project description:Mice with fat-specific disruption of the insulin receptor gene (FIRKO mice) have low fat mass, and are protected against obesity and obesity-related glucose intolerance. FIRKO mice also exhibit polarization of adipocytes into populations of large and small cells. Other PubMed identifiers for this study: 15131120,12110165,15131119

2007-04-06 | E-CBIL-23 | biostudies-arrayexpress

Beta cell-specific PAK1 enrichment ameliorates diet-induced glucose intolerance by promoting insulin biogenesis and minimizing beta cell apoptosis [RNA-Seq]

Project description:Aims/ hypothesis: p21 (Cdc42/Rac1) activated Kinase 1 (PAK1) is depleted in type 2 diabetic human islets compared to non-diabetic (ND) human islets, and acute PAK1 restoration to type 2 diabetic human islets can restore insulin secretory function ex vivo. We hypothesized that beta cell specific PAK1 enrichment in vivo carries the capacity to mitigate high-fat diet-induced glucose intolerance by increasing the functional beta cell mass. Methods: Type 2 diabetic or ND human islets expressing exogenous PAK1 specifically in beta cells were used for bulk RNA-sequencing (RNA-seq). Human EndoC-

2024-09-25 | GSE239381 | GEO

Beta cell-specific PAK1 enrichment ameliorates diet-induced glucose intolerance by promoting insulin biogenesis and minimizing beta cell apoptosis [ChIP-Seq]

2024-09-25 | GSE239306 | GEO

Neuronal overexpression of insulin receptor substrate 2 leads to increased fat mass, insulin resistance, and glucose intolerance during aging.

Project description:The insulin receptor substrates (IRS) are adapter proteins mediating insulin's and IGF1's intracellular effects. Recent data suggest that IRS2 in the central nervous system (CNS) is involved in regulating fuel metabolism as well as memory formation. The present study aims to specifically define the role of chronically increased IRS2-mediated signal transduction in the CNS. We generated transgenic mice overexpressing IRS2 specifically in neurons (nIRS2 (tg)) and analyzed these in respect to energy metabolism, learning, and memory. Western blot (WB) analysis of nIRS2 (tg) brain lysates revealed increased IRS2 downstream signaling. Histopathological investigation of nIRS2 (tg) mice proved unaltered brain development and structure. Interestingly, nIRS2 (tg) mice showed decreased voluntary locomotoric activity during dark phase accompanied with decreased energy expenditure (EE) leading to increased fat mass. Accordingly, nIRS2 (tg) mice develop insulin resistance and glucose intolerance during aging. Exploratory behavior, motor function as well as food and water intake were unchanged in nIRS2 (tg) mice. Surprisingly, increased IRS2-mediated signals did not change spatial working memory in the T-maze task. Since FoxO1 is a key mediator of IRS2-transmitted signals, we additionally generated mice expressing a dominant negative mutant of FoxO1 (FoxO1DN) specifically in neurons. This mutant mimics the effect of increased IRS2 signaling on FoxO-mediated transcription. Interestingly, the phenotype observed in nIRS2 (tg) mice was not present in FoxO1DN mice. Therefore, increased neuronal IRS2 signaling causes decreased locomotoric activity in the presence of unaltered exploratory behavior and motor coordination that might lead to increased fat mass, insulin resistance, and glucose intolerance during aging independent of FoxO1-mediated transcription.

| S-EPMC3776092 | biostudies-literature

Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition

Project description:Global energy balance in mammals is controlled by the actions of circulating hormones that coordinate fuel production and utilization in metabolically active tissues. Bone-derived osteocalcin, in its undercarboxylated, hormonal form, regulates fat deposition and is a potent insulin secretagogue. Here, we show that insulin receptor (IR) signaling in osteoblasts controls osteoblast development and osteocalcin expression by suppressing the Runx2 inhibitor Twist-2. Mice lacking IR in osteoblasts have low circulating undercarboxylated osteocalcin and reduced bone acquisition due to decreased bone formation and deficient numbers of osteoblasts. With age, these mice develop marked peripheral adiposity and hyperglycemia accompanied by severe glucose intolerance and insulin resistance. The metabolic abnormalities in these mice are improved by infusion of exogenous under-carboxylated osteocalcin. These results indicate the existence of a bone-pancreas endocrine loop through which insulin signaling in the osteoblast ensures osteoblast differentiation and stimulates osteocalcin production, which in turn regulates insulin sensitivity and pancreatic insulin secretion to control glucose homeostasis. We used microarrays to detail the global gene expression changes in response to insulin acting through insulin receptor in osteoblasts and identified distinct genes specifically involved in bone remodeling process. 4 groups and 3 time points (0h as a control, 6h, 12h, and 24h)

2010-05-27 | E-GEOD-21710 | biostudies-arrayexpress

Rescue of insulin receptor condensates in insulin resistant cells

Project description:Rescue of insulin receptor condensates in insulin resistant cells

| PRJNA750707 | ENA