Inhibition of Monoacylglycerol Lipase Activity Decreases Glucose-Stimulated Insulin Secretion in INS-1 (832/13) Cells and Rat Islets

Berdan, Charles A.; Erion, Karel; Burritt, Nathan E.; Corkey, Barbara E.; Deeney, Jude T.

doi:10.1371/journal.pone.0149008

Cited by 18 publications

(13 citation statements)

References 41 publications

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“…The possibility that environmental impacts may lead to changes in circulating redox, is potentially an important and unrecognized form of inter-organ communication. More detailed investigations on pancreatic βcell insulin secretion support such possibilities (Corkey, 2012a,b;Berdan et al, 2016;Erion and Corkey, 2018).…”

Section: Environmental Factors Impact β-Cells and Adipocytesmentioning

confidence: 95%

“…MOG also increases the mitochondrial redox state and interestingly, basal insulin secretion, while ROS scavengers abrogate secretion. It was not determined precisely whether MOG or a compound derived from MOG was responsible for the increases in ROS since MOG is readily metabolized to glycerol and LC-CoA (Saadeh et al, 2012;Berdan et al, 2016).…”

Section: Mono-oleoyl Glyceride (Mog) Stimulates Basal Insulin Secretionmentioning

confidence: 99%

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The Redox Communication Network as a Regulator of Metabolism

Corkey

Deeney

2020

Front. Physiol.

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Key tissues are dysfunctional in obesity, diabetes, cardiovascular disease, fatty liver and other metabolic diseases. Focus has centered on individual organs as though each was isolated. Attention has been paid to insulin resistance as the key relevant pathosis, particularly insulin receptor signaling. However, many tissues play important roles in synergistically regulating metabolic homeostasis and should be considered part of a network. Our approach identifies redox as an acute regulator of the greater metabolic network. Redox reactions involve the transfer of electrons between two molecules and in this work refer to commonly shared molecules, reflective of energy state, that can readily lose electrons to increase or gain electrons to decrease the oxidation state of molecules including NAD(P), NAD(P)H, and thiols. Metabolism alters such redox molecules to impact metabolic function in many tissues, thus, responding to anabolic and catabolic stimuli appropriately and synergistically. It is also important to consider environmental factors that have arisen or increased in recent decades as putative modifiers of redox and reactive oxygen species (ROS) and thus metabolic state. ROS are highly reactive, controlled by the thiol redox state and influence the function of thousands of proteins. Lactate (L) and pyruvate (P) in cells are present in a ratio of about 10 reflective of the cytosolic NADH to NAD ratio. Equilibrium is maintained in cells because lactate dehydrogenase is highly expressed and near equilibrium. The major source of circulating lactate and pyruvate is muscle, although other tissues also contribute. Acetoacetate (A) is produced primarily by liver mitochondria where β-hydroxybutyrate dehydrogenase is highly expressed, and maintains a ratio of β-hydroxybutyrate (β) to A of about 2, reflective of the mitochondrial NADH to NAD ratio. All four metabolites as well as the thiols, cysteine and glutathione, are transported into and out of cells, due to high expression of relevant transporters. Our model supports regulation of all collaborating metabolic organs through changes in circulating redox metabolites, regardless of whether change was initiated exogenously or by a single organ. Validation of these predictions suggests novel ways to understand function by monitoring and impacting redox state.

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Section: Environmental Factors Impact β-Cells and Adipocytesmentioning

confidence: 95%

Section: Mono-oleoyl Glyceride (Mog) Stimulates Basal Insulin Secretionmentioning

confidence: 99%

The Redox Communication Network as a Regulator of Metabolism

Corkey

Deeney

2020

Front. Physiol.

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“…Importantly, Mgll, which encodes monoacylglycerol lipase that catalyzes the conversion of monoacylglycerides to free fatty acids and glycerol was significantly increased. Mgll is required for lipolysis and improved glucose homeostasis in mice on HFD [47, 48], an infection driven increase was validated by RT-qPCR (Figure 2L). In addition, Slc1a3, which encodes for the glutamate aspartate transporter 1 that is localized in the inner mitochondria membrane as part of the malate-aspartate shuttle and is relevant for amino acid homeostasis in adipocytes, was significantly altered in our model, and was further validated by RT-qPCR (Figure 2M).…”

Section: Resultsmentioning

confidence: 99%

Schistosoma mansoniinfection reprograms the metabolic potential of the myeloid lineage in a mouse model of metabolic syndrome

Cortés-Selva

Gibbs

Maschek

et al. 2020

Preprint

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44 45 Despite strong evidence that helminth infections are protective against the development of 46 metabolic disease, a major gap exists in understanding the mechanism(s) underlying this. We 47 have previously found that Schistosoma mansoni induces profound alterations to the metabolic 48 transcriptome of hepatic macrophages and protects male ApoE -/on high fat diet from the 49 development of obesity, glucose intolerance, and atherosclerosis. Here we demonstrate that 50 macrophages derived from the bone marrow (BMDM) of S. mansoni infected male ApoE -/mice 51 have dramatically increased mitochondrial respiration and mitochondrial mass compared to those 52 from uninfected mice. This change is accompanied by increased glucose and palmitate shuttling 53 into TCA cycle intermediates and decreased accumulation of cellular cholesterol esters. The 54 systemic effects of metabolic modulation by schistosome infection are a function of biological 55 sex, where schistosome infection protects ApoE -/male mice from obesity, glucose intolerance, 56 and increased serum triglycerides, but not female mice. The sex-dependent effects of infection 57 extend to myeloid cells specifically, where metabolic reprogramming leads to opposite 58 cholesterol phenotypes in BMDM from infected females and males. Finally, we demonstrate that 59 the metabolic reprogramming of male myeloid cells is transferrable via bone marrow 60 transplantation to an uninfected host, indicating maintenance of reprogramming in the absence of 61 ongoing schistosome antigen exposure. This work provides strong evidence that S. 62 mansoni systemically reprograms the metabolism of the myeloid compartment in a sex-63 dependent manner. 64 65 Author Summary 66Globally helminth endemic regions have lower incidences of metabolic disease. Schistosomiasis 67 in particular has been shown to protect male mice from the development of atherosclerosis, 68 diabetes and obesity while altering the metabolism of liver macrophages. In this present study we 69 sought to understand if metabolic modulation occurs systemically, and if these effects occur in 70 females as well. We have found for the first time that macrophages generated from bone marrow 71 myeloid progenitors from infected male mice have long-lived increases in their basal metabolism 72 of lipids. We have also found that unlike male mice, female mice infected with Schistosoma 73 mansoni are not protected from the development of diabetes and obesity. S. mansoni infection 74 induces opposite changes to macrophage transcription and metabolism in males and females. 75Importantly we demonstrate that the changes to male macrophage metabolism can be transferred 76to an uninfected host. This suggests that metabolic reprogramming is long-lived without 77 exposure to active infection, and the development of a memory-like phenotype. 78 79 80 Introduction 81 82 Cardiovascular disease (CVD) is the leading worldwide cause of mortality [1, 2]. In the United 83States, 65% of adults diagnosed with diabetes have elevated LDL cholestero...

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“…Thus, it was shown that MAGL inhibition with URB602, which is a highly non‐specific inhibitor, was found to enhance 2‐AG levels and insulin secretion in MIN6 β‐cells and isolated human islets . In a recent study, it was argued that MAGL also regulates insulin secretion from INS‐1(832/13) cells and isolated rat islets . These authors showed that pharmacological inhibition of MAGL led to decrease, but not increase in GSIS .…”

Section: Introductionmentioning

confidence: 99%

“…In a recent study, it was argued that MAGL also regulates insulin secretion from INS‐1(832/13) cells and isolated rat islets . These authors showed that pharmacological inhibition of MAGL led to decrease, but not increase in GSIS . However, because of high concentrations of the inhibitors used in their study the possibility of inhibition of other lipases such as HSL that produces MAG and unspecific effects, cannot be eliminated.…”

Section: Introductionmentioning

confidence: 99%

Monoacylglycerol signalling and ABHD6 in health and disease

Poursharifi

Madiraju

2017

Diabetes Obesity Metabolism

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Lipid metabolism dysregulation underlies chronic pathologies such as obesity, diabetes and cancer. Besides their role in structure and energy storage, lipids are also important signalling molecules regulating multiple biological functions. Thus, understanding the precise lipid metabolism enzymatic steps that are altered in some pathological conditions is helpful for designing better treatment strategies. Several monoacylglycerol (MAG) species are only recently being recog- are still being discovered, indicating the complexity, Abbreviations:

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Inhibition of Monoacylglycerol Lipase Activity Decreases Glucose-Stimulated Insulin Secretion in INS-1 (832/13) Cells and Rat Islets

Cited by 18 publications

References 41 publications

The Redox Communication Network as a Regulator of Metabolism

The Redox Communication Network as a Regulator of Metabolism

Schistosoma mansoniinfection reprograms the metabolic potential of the myeloid lineage in a mouse model of metabolic syndrome

Monoacylglycerol signalling and ABHD6 in health and disease

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