RGD Reference Report - Hepatosteatosis and hepatic insulin resistance are blunted by argirein, an anti-inflammatory agent, through normalizing endoplasmic reticulum stress and apoptosis in diabetic liver.

General

Hepatosteatosis and hepatic insulin resistance are blunted by argirein, an anti-inflammatory agent, through normalizing endoplasmic reticulum stress and apoptosis in diabetic liver.
Authors:	Shi, FH Wu, Y Dai, DZ Cong, XD Zhang, YM Dai, Y
Citation:	Shi FH, etal., J Pharm Pharmacol. 2013 Jun;65(6):916-27. doi: 10.1111/jphp.12051. Epub 2013 Mar 25.
RGD ID:	11354957
Pubmed:	PMID:23647685 (View Abstract at PubMed)
DOI:	DOI:10.1111/jphp.12051 (Journal Full-text)
OBJECTIVES: Insulin resistance represents a mechanism underlying defect metabolism of carbohydrate and lipid linked to inflammatory reactions in diabetic liver. We hypothesized that the changes may be secondary to endoplasmic reticulum (ER) stress, which could be alleviated by either argirein or valsartan. METHODS: Hepatosteatosis in diabetic liver was induced in rats fed with a high-fat diet (HFD) for 12 weeks combined with a single low dose of streptozotocin (STZ 35 mg/kg, ip). Interventions (mg/kg/d, po)with either argirein (50, 100 and 200) or valsartan (12) were conducted in the last 4 weeks. KEY FINDINGS: In diabetic liver fat was significantly accumulated in association with elevated hepatic glucose, serum insulin and homeostasis model assessment of insulin resistance value. Downregulated glucose transporter 4, insulin receptor substrate-1 and leptin receptor (P < 0.01) were found relative to normal, where DNA ladder, downregulated B cell lymphoma/leukemia-2, upregulated B cell lymphoma/leukemia-2 Associated X protein and upregulated ER stress chaperones such as Bip/GRP78 (also known as Binding Protein, BiP), PKR-like ER kinase (PERK), p-PERK/PERK and C/EBP homologous protein were significant. These abnormalities were significantly ameliorated by argirein and valsartan. CONCLUSIONS: Hepatosteatosis induced by HFD/low STZ manifests insulin resistance and apoptosis, linked to an entity of low-grade inflammation due to activated ER stress sensors. With anti-inflammatory activity either argirein or valsartan blunts hepatosteatosis through normalizing ER stress and apoptosis in the diabetic liver.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
steatotic liver disease		ISO	Hspa5 (Rattus norvegicus)	11354957; 11354957	associated with Diabetes Mellitus more ...	RGD
steatotic liver disease		IEP		11354957	associated with Diabetes Mellitus more ...	RGD

Objects Annotated

Genes (Rattus norvegicus)

Hspa5 (heat shock protein family A (Hsp70) member 5)

Genes (Mus musculus)

Hspa5 (heat shock protein 5)

Genes (Homo sapiens)

HSPA5 (heat shock protein family A (Hsp70) member 5)

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Hepatosteatosis and hepatic insulin resistance are blunted by argirein, an anti-inflammatory agent, through normalizing endoplasmic reticulum stress and apoptosis in diabetic liver.