Insulin Protects Pancreatic Acinar Cells from Palmitoleic Acid-induced Cellular Injury

Samad, Aysha; James, Andrew; Wong, James R.; Mankad, Parini; Whitehouse, John; Patel, Waseema; Alves-Simoes, Marta; Siriwardena, Ajith K.; Bruce, Jason I.E.

doi:10.1074/jbc.m114.589440

Cited by 44 publications

(44 citation statements)

References 58 publications

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“…UFAs inhibit mitochondrial complexes I and V 1. While we noted early caspase 3/7 activation in acini, this was not sustained (results not shown), perhaps due to concurrent ATP depletion104 115 116 triggering the necrosis noted at 5 h. Noting this, and the dual annexin V and PI staining of PBMCs, TUNEL positivity in lungs and renal tubules (which are also KIM-1 positive), the likely mode of injury induced by UFAs is necro-apoptotic.…”

Section: Discussionmentioning

confidence: 64%

Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

Noel

Patel

Durgampudi

et al. 2014

Gut

133

147

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Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP.

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Section: Discussionmentioning

confidence: 64%

Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

Noel

Patel

Durgampudi

et al. 2014

Gut

133

147

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“…First, increasing extracellular magnesium reduces pancreatitis responses in rodent acinar cells including pathologic calcium signaling and lessens the severity of in vivo pancreatitis in rodent models113, 114; it now is being examined for its potential role in reducing PEP 112 . Insulin recently was shown to decrease calcium levels caused by induction of pancreatitis responses in acinar cells and reduce other cellular pancreatitis injuries 115, 116. These actions appear to be linked to a plasma-membrane calcium pump.…”

Section: Has Anything Been Identified In Animal Models That Clearly Imentioning

confidence: 99%

Do Animal Models of Acute Pancreatitis Reproduce Human Disease?

Gorelick

Lerch

2017

Cellular and Molecular Gastroenterology and Hepatology

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Acute pancreatitis is currently the most common cause of hospital admission among all nonmalignant gastrointestinal diseases. To understand the pathophysiology of the disease and as a potential step toward developing targeted therapies, attempts to induce the disease experimentally began more than 100 years ago. Recent decades have seen progress in developing new experimental pancreatitis models as well as elucidating many underlying cell biological and pathophysiological disease mechanisms. Some models have been developed to reflect specific causes of acute pancreatitis in human beings. However, the paucity of data relating to the molecular mechanisms of human disease, the likelihood that multiple genetic and environmental factors affect the risk of disease development and its severity, and the limited information regarding the natural history of disease in human beings make it difficult to evaluate the value of disease models. Here, we provide an overview of key models and discuss our views on their strengths for characterizing cell biological disease mechanisms or for identifying potential therapeutic targets. We also acknowledge their limitations.

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“…Epidemiological studies reported a positive correlation between high circulating 16:1n-7 levels and obesity (Gong et al, 2011), pancreatitis (Samad et al, 2014), hepatic steatosis (Lee et al, 2015), and cardiovascular disease (Warensjo et al, 2008). Other studies showed that sensitivity to insulin in peripheral tissues is not associated with the availability of 16:1n-7 in plasma of obese patients (Fabbrini et al, 2011), and that high levels of this fatty acid in red blood cells correlate with severity of inflammation (Perreault et al, 2014) and greater risk of diabetes (Zong et al, 2013).…”

Section: Introductionmentioning

confidence: 97%

Foamy Monocytes Are Enriched in cis -7-Hexadecenoic Fatty Acid (16:1n-9), a Possible Biomarker for Early Detection of Cardiovascular Disease

Guijas

Meana

Astudillo

et al. 2016

Cell Chemical Biology

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Human monocytes respond to arachidonic acid, a secretory product of endothelial cells, by activating the de novo pathway of fatty acid biosynthesis, resulting in the acquisition of a foamy phenotype due to accumulation of cytoplasmic lipid droplets. Recruitment of foamy monocytes to endothelium is a key step in the formation of atherosclerotic plaques. Here we describe that lipid droplets of foamy monocytes are enriched in a rather uncommon fatty acid, cis-7-hexadecenoic acid (16:1n-9), a positional isomer of palmitoleic acid. 16:1n-9 was found to possess an anti-inflammatory activity both in vitro and in vivo that is comparable with that of omega-3 fatty acids and clearly distinguishable from the effects of palmitoleic acid. Selective accumulation in neutral lipids of phagocytic cells of an uncommon fatty acid reveals an early phenotypic change that may provide a biomarker of proatherogenicity, and a potential target for intervention in the early stages of cardiovascular disease.

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Insulin Protects Pancreatic Acinar Cells from Palmitoleic Acid-induced Cellular Injury

Cited by 44 publications

References 58 publications

Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

Do Animal Models of Acute Pancreatitis Reproduce Human Disease?

Foamy Monocytes Are Enriched in cis -7-Hexadecenoic Fatty Acid (16:1n-9), a Possible Biomarker for Early Detection of Cardiovascular Disease

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