The islet beta-cell.
ABSTRACT The beta-cell is one of four major types of cells present in the islets of Langerhans, which are islands of cells distributed throughout the endocrine pancreas in most mammals. The beta-cell synthesizes and secretes the hormone insulin mainly in response to glucose but also in response to several nutrients, hormones and nervous stimuli. In adult rodents the beta-cell has a slow mitotic rate. Recent studies provide novel insights into the functions of the beta-cell. The presence of functional insulin-like growth factor-1 and insulin receptors and components of their signaling pathway indicate an important role for insulin/IGF-1 signaling in the regulation of beta-cell function. Further, the recent discovery of glucokinase (GK) and the ATP-dependent potassium channels on insulin secretory granules, the detection of AMP-protein kinase in the beta-cell and the identification of a new beta-cell transcription factor, mMafA, are some exciting new areas of research currently underway to further understand the complex pathways that regulate the functions of beta-cells.
- SourceAvailable from: Jeroen Aerssens[Show abstract] [Hide abstract]
ABSTRACT: Insulin resistance and obesity are underlying causes of type 2 diabetes and therefore much interest is focused on the potential genes involved. A series of anthropometric and metabolic characteristic were measured in 240 MZ and 112 DZ twin pairs recruited from the East Flanders Prospective Twin Survey. Microsatellite markers located close to ABCC8, ADIPOQ, GCK, IGF1, IGFBP1, INSR, LEP, LEPR, PPARgamma and the RETN gene were genotyped. Univariate single point variance components linkage analyses were performed using two methods: (1) the standard method, only comprising the phenotypic and genotypic data of the DZ twin pairs and (2) the extended method, also incorporating the phenotypic data of the MZ twin pairs. Suggestive linkages (LOD > 1) were observed between the ABCC8 marker and waist-to-hip ratio and HDL-cholesterol levels. Both markers flanking ADIPOQ showed suggestive linkage with triglycerides levels, the upstream marker also with body mass and HDL-cholesterol levels. The IGFBP1 marker showed suggestive linkage with fat mass, fasting insulin and leptin levels and the LEP marker showed suggestive linkage with birth weight. This study suggests that DNA variants in ABCC8, ADIPOQ, IGFBP1 and LEP gene region may predispose to type 2 diabetes. In addition, the two methods used to perform linkage analyses yielded similar results. This was however not the case for birth weight where chorionicity seems to be an important confounder.Twin Research and Human Genetics 11/2008; 11(5):505-16. DOI:10.1375/twin.11.5.505 · 1.92 Impact Factor
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ABSTRACT: Transplantation of functional islets of Langerhans may emerge as a useful therapy for some patients with type 1 diabetes mellitus (DM), but donor islet shortages motivate the search for new sources of transplantable islets. Pluripotent embryonic stem (ES) cells are expandable in culture and have the potential to give rise to all cell types in the body. The recent isolation of pluripotent ES cells from humans has generated excitement over the possibility of engineering glucose-responsive islet replacement tissue from these cells in large quantities. In this study, we review the recent advances in generating insulin-producing cells (IPC) from mouse and human ES (hES) cells.Pediatric Diabetes 02/2004; 5 Suppl 2:5-15. DOI:10.1111/j.1399-543X.2004.00074.x · 2.13 Impact Factor
Article: Insulin and insulin resistance.[Show abstract] [Hide abstract]
ABSTRACT: As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalization, urbanisation and industrialization have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits.The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists 06/2005; 26(2):19-39.