Insulin granule dynamics in pancreatic beta cells

Rorsman, Patrik; Renström, Erik

doi:10.1007/s00125-003-1153-1

Cited by 734 publications

(803 citation statements)

References 129 publications

(187 reference statements)

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“…In view of the present knowledge on granule dynamics and distinct pools, it has been speculated that the proteins of the exocytotic machinery that are implicated in the rate-limiting priming of secretory granules are strong candidates for the triggering of beta cell dysfunctions associated with type 2 diabetes [40]. In the RIP-REST transgenic mice that specifically express REST in beta cells, expression of multiple REST target genes, including those coding for the major proteins controlling exocytosis, was decreased.…”

Section: Discussionmentioning

confidence: 99%

Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells

et al. 2008

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Aims/hypothesis The expression of several neuronal genes in pancreatic beta cells is due to the absence of the transcription factor repressor element 1 (RE-1) silencing transcription factor (REST). The identification of these traits and their functional significance in beta cells has only been partly elucidated. Herein, we investigated the biological consequences of a repression of REST target genes by expressing REST in beta cells. Methods The effect of REST expression on glucose homeostasis, insulin content and release, and beta cell mass was analysed in transgenic mice selectively expressing REST in beta cells. Relevant target genes were identified in INS-1E and primary beta cells expressing REST. Results Transgenic mice featuring a beta cell-targeted expression of REST exhibited glucose intolerance and reduced beta cell mass. In primary beta cells, REST repressed several proteins of the exocytotic machinery, including synaptosomal-associated protein (SNAP) 25, synaptotagmin (SYT) IV, SYT VII, SYT IX and complexin II; it impaired first and second phases of insulin secretion. Using RNA interference in INS-1E cells, we showed that SYT IV and SYT VII were implicated in the control of insulin release.

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Section: Discussionmentioning

confidence: 99%

Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells

et al. 2008

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“…We refer the reader to comprehensive reviews on the topic for insulin secretion specifically (Lang, 1999;Rorsman and Renstrom, 2003) and for the general mechanism of exocytosis (Seino and Shibasaki, 2005;Ungermann and Langosch, 2005). However, as GLP-1 exerts effects at various stages of this process we present a brief summary of what is known about the mechanism.…”

Section: Exocytosis Of Insulin Secretory Vesiclesmentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

583

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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“…Ca 2+ stimulates insulin secretion by regulating docking and initiating fusion of secretory granules with the plasma membrane, a process mediated by SNARE proteins (Rorsman and Renström, 2003;MacDonald and Rorsman, 2007). entry is actually directed to the sites of exocytosis via the binding of the L-type Ca 2+ channels to SNARE proteins (Wiser et al, 1999).…”

Section: The Cytoplasmic Ca 2+ Concentrationmentioning

confidence: 99%

Oscillatory control of insulin secretion

Tengholm

Gylfe

2009

Molecular and Cellular Endocrinology

163

169

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Pulsatile insulin secretionSince insulin is the only blood glucose-lowering hormone, its secretion is essential for glucose homeostasis, and disturbances are associated with glucose intolerance and diabetes.Glucose is the major stimulus for insulin release but secretion is enhanced also by other nutrients and is under stimulatory and inhibitory control by hormones and neurotransmitters.Although the external factors are essential determinants of insulin secretion, there are also input-independent variations in hormone release. Regular oscillations of the circulating insulin concentrations in normal subjects consequently occur without accompanying changes

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Insulin granule dynamics in pancreatic beta cells

Cited by 734 publications

References 129 publications

Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells

Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Oscillatory control of insulin secretion

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