... and environmental triggers. Genome-wide association studies revealed that by and large, gene variants associated with type 2 diabetes are implicated in pancreatic β-cell function, suggesting that the β-cell may be the weakest link in the chain of events that results in diabetes. Thus, it is critical to understand...

...Timothy J. Pullen; Guy A. Rutter The progression of Type 2 diabetes is accompanied by diminishing islet β-cell mass and function. It has been proposed that β-cells are lost not only through apoptosis, but also by dedifferentiating into progenitor-like cells. There is therefore much interest...

...Jonathan M. Locke; Lorna W. Harries Recent studies in mouse, involving the β-cell-specific deletion of Dicer1, have highlighted the crucial role of miRNAs (microRNAs) in regulating insulin secretion and consequently Type 2 diabetes. Identifying the individual miRNAs involved in human islet...

...Vincent Poitout The glucolipotoxicity hypothesis postulates that chronically elevated levels of glucose and fatty acids adversely affect pancreatic β-cell function and thereby contribute to the deterioration of insulin secretion in Type 2 diabetes. Whereas ample experimental evidence in in vitro...

...Ruth Brownlie; Rachel M. Mayers; Jackie A. Pierce; Anna E. Marley; David M. Smith GPR40 (G-protein-coupled receptor 40) has been shown to be a physiologically relevant receptor for long-chain fatty acids. It is a family A G-protein-coupled receptor highly expressed in the β-cell where it increases...

...Guy A. Rutter; F. Susan Wong Defective insulin secretion is a hallmark of all forms of diabetes. Whereas Type 1 diabetes has long been known to result from the immune-mediated destruction of β-cells, Type 2 diabetes appears to involve both loss of β-cell mass and glucose sensitivity in the face...

.... Thus, if cell therapy should be widely available, it will require an unlimited source of cells to serve as a ‘biological’ insulin pump. At this time, the development of β-cells from hESCs (human embryonic stem cells) has emerged as the most attractive alternative. It is envisioned that ultimate success...

...Susan Bonner-Weir; Akari Inada; Shigeru Yatoh; Wan-Chun Li; Tandy Aye; Elena Toschi; Arun Sharma The regenerative process in the pancreas is of particular interest, since diabetes, whether Type 1 or Type 2, results from an inadequate amount of insulin-producing β-cells. Islet neogenesis...

...F. Susan Wong; L. Khai Siew; Li Wen The autoimmune attack on pancreatic β-cells is orchestrated by a variety of cells that produce cytokines and other toxic mediators. CD8 + T-cells work together with other lymphocytes and antigen-presenting cells to mediate this damage and have been shown...

...Shanta J. Persaud; Dany Muller; Peter M. Jones Studies in transgenic animals, rodent insulin-secreting cell lines and rodent islets suggest that insulin acts in an autocrine manner to regulate β-cell mass and gene expression. Very little is known about the in vitro roles played by insulin in human...

... it is now clear that abnormal pancreatic development can give rise to specific forms of diabetes in humans; and finally, because, if we want to define new treatments for diabetes based on cell therapy or regenerative medicine, we will have to understand in detail how β-cells develop. In the present paper...

..., has led to improved treatment options for patients. The studies of monogenic forms of β-cell dysfunction are no exception. Naturally occurring mutations in the gene for the β-cell enzyme glucokinase ( GCK ) result in both hyper- and hypo-glycaemia. Over 200 mutations have been described, and careful...

...Conny Gysemans; Hanne Callewaert; Lutgart Overbergh; Chantal Mathieu IFNγ (interferon γ), a cytokine typically secreted by infiltrating immune cells in insulitis in Type 1 diabetes, is by itself not detrimental to β-cells, but, together with other cytokines, such as IL-1β (interleukin 1β) and TNFα...

... and insulin gene expression while slightly potentiating glucose stimulated changes in intracellular free Ca 2+ concentrations. β-cell diabetes forkhead box O1 (FoxO1) insulin secretion T-cell factor 7-like 2 (TCF7L2) Type 2 diabetes mellitus (T2DM) 1 These authors contributed equally...

...Danielle Melloul Apoptotic β-cell death appears to be central to the pathogenesis of Type 1 diabetes mellitus and in islet graft rejection. The β-cell destruction is partially mediated by cytokines, such as IL-1β (interleukin 1β), TNFα (tumour necrosis factor α) and IFN-γ (interferon γ). IL-1β...

...H. Freeman; K. Shimomura; R.D. Cox; F.M. Ashcroft This paper reviews recent studies on the role of Nnt (nicotinamide nucleotide transhydrogenase) in insulin secretion and detoxification of ROS (reactive oxygen species). Glucose-stimulated insulin release from pancreatic β-cells is mediated...

...K. Bender; P. Newsholme; L. Brennan; P. Maechler The coupling of cytosolic glycolytic NADH production with the mitochondrial electron transport chain is crucial for pancreatic β-cell function and energy metabolism. The activity of lactate dehydrogenase in the β-cell is low, thus glycolysis-derived...

...R. An; G. da Silva Xavier; H.-X. Hao; F. Semplici; J. Rutter; G.A. Rutter The transcription factor PDX-1 ( p ancreatic d uodenal homeobo x -1) is required for normal pancreatic development and for the function of insulin-producing islet β-cells in mammals. We have shown previously that glucose...

...G.A. Rutter; M.K. Loder; M.A. Ravier Minute-to-minute control of the release of insulin by pancreatic β-cells in response to glucose or other stimuli requires the precise delivery of large dense-core vesicles to the plasma membrane and regulated exocytosis. At present, the precise spatial...

...G.A. Rutter; A. Varadi; T. Tsuboi; L. Parton; M. Ravier Defective insulin secretion from pancreatic islet β-cells is a sine qua non of Type II (non-insulin-dependent) diabetes. Digital imaging analysis of the nanomechanics of individual exocytotic events, achieved using total internal reflection...

...R. N. Kulkarni The insulin/insulin-like growth factor-1 (IGF-1) signalling pathways are present in most mammalian cells and play important roles in the growth and metabolism of tissues. Most proteins in these pathways have also been identified in the β-cells of the pancreatic islets. Tissue...