Dataset Information

Protein kinase C epsilon deletion in AgRP neurons modulates hypothalamic glucose sensing and improves glucose tolerance in mice

ABSTRACT: Total and phosphoproteomic analysis of liver and white adipose tissue from mice with specific deletion of protein kinase C epsilon in AgRP nerons of the hypothalamus, 30 min after i.p. injection with glucose.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epididymal White Adipose Tissue

DISEASE(S): Obesity

SUBMITTER: Carsten Schmitz-Peiffer

LAB HEAD: Carsten Schmitz-Peiffer

PROVIDER: PXD065137 | Pride | 2026-02-09

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20240722_AgRP_Liver_30min_Glc_Total_report.unique_genes_matrix.tsv	Tabular
	20240722_Exploris480_CSP_AgRP_Liver_30minGlc_1.raw	Raw
	20240722_Exploris480_CSP_AgRP_Liver_30minGlc_10.raw	Raw
	20240722_Exploris480_CSP_AgRP_Liver_30minGlc_11.raw	Raw
	20240722_Exploris480_CSP_AgRP_Liver_30minGlc_12.raw	Raw

Items per page:

1 - 5 of 81

Publications

Protein kinase C epsilon deletion in AgRP neurons modulates hypothalamic glucose sensing and improves glucose tolerance in mice.

Brandon Amanda E AE Yan Chenxu C Zhang Xuan X Ip Chi Kin CK Gao Zhongmin Z Lee Nicola J NJ Marian Oana C OC Perez Alex A Don Anthony S AS Herzog Herbert H Small Lewin L Shi Yan-Chuan YC Schmitz-Peiffer Carsten C

Molecular metabolism 20260113

<h4>Objectives</h4>Global but not liver-specific deletion of protein kinase C epsilon (PKCε) improves glucose tolerance in fat-fed mice, suggesting that extra-hepatic tissues are involved. AgRP neurons within the arcuate nucleus (ARC) of the hypothalamus can affect glucose homeostasis acutely, in addition to their role in energy homeostasis. We therefore deleted PKCε specifically in AgRP neurons to examine its effects at this site.<h4>Methods</h4>Fat-fed AgRP-PKCε<sup>-/-</sup> mice were subject ...[more]

PMID: 41539424

Similar Datasets

Project description:Protein kinase C epsilon (PKCe) has been shown to play a causative role in the generation of glucose intolerance and insulin resistance. Tissue-specific deletion of PKC indicates multiple sites of action, highlighting the kinase as a potential target for the treatment of type 2 diabetes. CIDD-0150612 has been developed as a PKCe inhibitor from the Rho-associated, coiled-coil containing protein kinase (ROCK) inhibitor Y-27632. Here, we examined the effects of a CIDD-0150612 on insulin action in palmitate-treated HepG2 hepatocytes in vitro and on glucose homeostasis in fat-fed mice in vivo. HepG2 cells were treated with palmitate and CIDD-0150612, and stimulated with insulin. Insulin signalling was examined by immunoblotting and glucose incorporation into glycogen was measured using glucose tracer. Mice were fed a high-fat diet for 8 weeks and treated with CIDD-0150612 in the final 2 weeks, prior to glucose tolerance tests, insulin challenge and tissue harvest. Proteomic and phosphoproteomic analysis was carried out on liver proteins by liquid chromatography with tandem mass spectrometry. CIDD-0150612 had no effect on insulin-stimulated insulin receptor or IRS-1 tyrosine phosphorylation in lipid-treated hepatocytes. However, the inhibitor promoted Akt phosphorylation in a highly insulin-dependent manner, and reversed the inhibition of insulin-stimulated Akt phosphorylation and glucose incorporation into glycogen by palmitate. Fat-fed mice treated with CIDD-0150612 had reduced body fat and body weight, but not lean mass, compared with vehicle-treated littermates. Mice treated acutely with CIDD-0150612 exhibited elevated fasting blood glucose. However, mice studied 24h after the last dose had lower fasting glucose and improved glucose tolerance with a lower insulin excursion. CIDD-0150612 treatment reduced skeletal muscle triglyceride content, but did not affect insulin signalling in liver or muscle in response to an insulin challenge. Proteomic analysis of liver from CIDD-0150612-treated fat-fed mice indicated a reduction in gluconeogenic gene expression and decreased phosphorylation of the transcription factor Foxk1. The PKCe inhibitor CIDD-0150612 had beneficial effects on insulin action in hepatocytes and on fat mass and glucose homeostasis in mice. Because certain effects, such as the reduction in fat mass, were not previously observed in studies of PKCe-deficient mice, off-target effects, most likely through residual ROCK1 inhibition, may be partly responsible.