Metabolomics applied to the pancreatic islet

Gooding, Jessica; Jensen, Mette V.; Newgard, Christopher B.

doi:10.1016/j.abb.2015.06.013

Cited by 36 publications

(35 citation statements)

References 104 publications

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“…Growing evidence implicates non-oxidative, anaplerotic metabolism of glucose as an important regulator of GSIS. In particular, the full GSIS response requires pyruvate carboxylase activity, efficient export of citrate and/or isocitrate from the mitochondria to the cytosol, and engagement of isocitrate with the cytosolic, NADP-dependent isocitrate dehydrogenase (IDH1 or ICDc) (Gooding et al, 2015; Ferdaoussi, et al 2015; Jensen et al, 2006; Jensen et al, 2008; Joseph et al, 2006; Lu et al, 2002; Ronnebaum et al, 2006). …”

Section: Introductionmentioning

confidence: 99%

Adenylosuccinate Is an Insulin Secretagogue Derived from Glucose-Induced Purine Metabolism

et al. 2015

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Pancreatic islet failure, involving loss of glucose-stimulated insulin secretion (GSIS) from islet β-cells, heralds the onset of type 2 diabetes (T2D). To search for mediators of GSIS, we performed metabolomics profiling of the insulinoma cell line 832/13, and uncovered significant glucose-induced changes in purine pathway intermediates, including a decrease in inosine monophosphate (IMP) and an increase in adenylosuccinate (S-AMP), suggesting a regulatory role for the enzyme that links the two metabolites, adenylosuccinate synthase (ADSS). Inhibition of ADSS or a more proximal enzyme in the S-AMP biosynthesis pathway, adenylosuccinate lyase, lowers S-AMP levels and impairs GSIS. Addition of S-AMP to the interior of patch-clamped human β-cells amplifies exocytosis, an effect dependent upon expression of sentrin/SUMO-specific protease 1 (SENP1). S-AMP also overcomes the defect in glucose-induced exocytosis in β–cells from a human donor with T2D. S-AMP is thus an insulin secretagogue capable of reversing β-cell dysfunction in T2D.

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Section: Introductionmentioning

confidence: 99%

Adenylosuccinate Is an Insulin Secretagogue Derived from Glucose-Induced Purine Metabolism

et al. 2015

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“…With this proviso, metabolomic studies reveal 5-to 20-fold increases in metabolites such as citrate, 2-oxoglutarate, and malate during the period following a low to high glucose transition (FIGURE 7B), although absolute quantitation is rarely applied (188,230,490). It should be noted that while the low to high glucose transition has attracted a vast range of papers, the reverse process, the depletion of metabolites on the return to basal glucose, has been largely neglected.…”

Section: A Citric Acid Cycle Derived Coupling Factors Pyruvate Carbmentioning

confidence: 99%

The Pancreatic β-Cell: A Bioenergetic Perspective

Nicholls

2016

Physiological Reviews

123

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The pancreatic ␤-cell secretes insulin in response to elevated plasma glucose. This review applies an external bioenergetic critique to the central processes of glucose-stimulated insulin secretion, including glycolytic and mitochondrial metabolism, the cytosolic adenine nucleotide pool, and its interaction with plasma membrane ion channels. The control mechanisms responsible for the unique responsiveness of the cell to glucose availability are discussed from bioenergetic and metabolic control standpoints. The concept of coupling factor facilitation of secretion is critiqued, and an attempt is made to unravel the bioenergetic basis of the oscillatory mechanisms controlling secretion. The need to consider the physiological constraints operating in the intact cell is emphasized throughout. The aim is to provide a coherent pathway through an extensive, complex, and sometimes bewildering literature, particularly for those unfamiliar with the field.

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“…For diabetes to occur, the function and/or mass of the pancreatic β-cells must be compromised (115–118). Importantly, attempts to understand the dynamic changes in islet mass expansion, as well as inflammatory responses within β-cells, have benefitted from the establishment of novel “omics” technologies (119–122). Our goal herein was to illustrate the outstanding ability of the endocrine pancreas to respond to various, albeit distinct, scenarios that require an increase in insulin production and release.…”

Section: Summary and Discussionmentioning

confidence: 99%

Pancreatic Islet Responses to Metabolic Trauma

Burke

Karlstad

Collier

2016

Shock

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Carbohydrate, lipid, and protein metabolism are largely controlled by the interplay of various hormones, which includes those secreted by the pancreatic islets of Langerhans. While typically representing only 1–2% of the total pancreatic mass, the islets have a remarkable ability to adapt to disparate situations demanding a change in hormone release, such as peripheral insulin resistance. There are many different routes to the onset of insulin resistance, including obesity, lipodystrophy, glucocorticoid excess, and the chronic usage of atypical anti-psychotic drugs. All of these situations are coupled to an increase in pancreatic islet size, often with a corresponding increase in insulin production. These adaptive responses within the islets are ultimately intended to maintain glycemic control and to promote macronutrient homeostasis during times of stress. Herein, we review the consequences of specific metabolic trauma that lead to insulin resistance and the corresponding adaptive alterations within the pancreatic islets.

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Metabolomics applied to the pancreatic islet

Cited by 36 publications

References 104 publications

Adenylosuccinate Is an Insulin Secretagogue Derived from Glucose-Induced Purine Metabolism

Adenylosuccinate Is an Insulin Secretagogue Derived from Glucose-Induced Purine Metabolism

The Pancreatic β-Cell: A Bioenergetic Perspective

Pancreatic Islet Responses to Metabolic Trauma

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