...Charles Affourtit; Ben Alberts; Jonathan Barlow; Jane E. Carré; Anthony G. Wynne The canonical model of glucose-stimulated insulin secretion (GSIS) by pancreatic β-cells predicts a glucose-induced rise in the cytosolic ATP/ADP ratio. Such bioenergetic sensitivity to metabolic fuel is unusual...

...Eleftheria Diakogiannaki; Noel G. Morgan Recent evidence indicates that treatment of pancreatic β-cells with long chain fatty acids can lead to the development of an ER (endoplasmic reticulum) stress response. This is manifest as the activation of some components of the PERK [RNA-dependent protein...

...Ning Li; Francesca Frigerio; Pierre Maechler Pancreatic β-cells are essential for the maintenance of glucose homoeostasis, and dysfunction of these insulin-secreting cells results in the development of diabetes. In the course of events leading from obesity to Type 2 diabetes, several mechanisms...

...Anath Shalev Glucotoxicity plays a major role in pancreatic β-cell apoptosis and diabetes progression, but the factors involved have remained largely unknown. Our recent studies have identified TXNIP (thioredoxin-interacting protein) as a novel pro-apoptotic β-cell factor that is induced by glucose...

... cascades triggered by occupation of cell surface receptors, but the cPKC (conventional PKC) and nPKC (novel PKC) isoforms are also responsive to fatty acid metabolites. PKC isoforms are involved in various aspects of pancreatic β-cell function, including cell proliferation, differentiation and death...

... to human neurodegenerative, inflammatory, cardiovascular and neoplastic diseases. The ER stress response has also been implicated in diabetes development, affecting both insulin production by pancreatic β-cells and insulin sensitivity in peripheral tissues. In the present mini-review, we focus on recent...

...Deirdre Keane; Philip Newsholme Both stimulatory and detrimental effects of NEFAs (non-esterified fatty acids) on pancreatic β-cells have been recognized. Acute exposure of the pancreatic β-cell to high glucose concentrations and/or saturated NEFAs results in a substantial increase in insulin...

.... 1 To who correspondence should be addressed (email timo.otonkoski@helsinki.fi ). 16 11 2007 © The Authors Journal compilation © 2008 Biochemical Society 2008 betacellulin epidermal growth factor (EGF) ErbB pancreatic β-cell transdifferentiation EGF (epidermal growth...

.... This insulin deficiency results from pancreatic β-cell dysfunction and death. Western diets rich in saturated fats cause obesity and insulin resistance, and increase levels of circulating NEFAs [non-esterified (‘free’) fatty acids]. In addition, they contribute to β-cell failure in genetically predisposed...

... below. Most of the research effort in the field of T1DM pathogenesis has focused on the immune system, with less attention paid to the pancreatic β-cells. The main form of β-cell death in the course of insulitis is apoptosis, which is triggered by contact with activated macrophages and T-cells...

...T.P. Herbert To ensure cellular survival to ER (endoplasmic reticulum) stress, PERK [PKR (double-stranded-RNA-dependent protein kinase)-like ER kinase], an ER transmembrane kinase, is activated as part of the unfolded protein response. PERK is highly expressed in pancreatic β-cells and is essential...

...D. Johnson; R.M. Shepherd; D. Gill; T. Gorman; D.M. Smith; M.J. Dunne GK (glucokinase) catalyses the phosphorylation of glucose to glucose 6-phosphate in glucosensitive cells. In pancreatic β-cells, this reaction is the rate-limiting step of insulin release. Recent work has led to the discovery...

...P. Maechler; P.B.M. de Andrade Pancreatic β-cells are able to respond to nutrients, principally glucose, as the primary stimulus for insulin exocytosis. This unique feature requires translation of metabolic substrates into intracellular messengers recognized by the exocytotic machinery. Central...

... and pancreatic β-cell glucose responsiveness. Mechanisms underlying β-cell dysfunction include glucose toxicity, lipotoxicity and β-cell hyperactivity. Defects at various sites in β-cell signal transduction pathways contribute, but no single lesion can account for the common form of Type 2 diabetes. Recent...

... by phosphorylating key enzymes of intermediate metabolism. Here we will discuss the recent evidence implicating AMPK in the regulation of gene expression in mammals, mainly in the liver and in the pancreatic β-cells. 1 To whom correspondence should be addressed (e-mail i.leclerc@bristol.ac.uk ). 19 10...