Ions, genes and insulin release: from basic science to clinical disease Based on the 1998 R. D. Lawrence Lecture

Mj, Dunne

doi:10.1046/j.1464-5491.2000.00247.x

Cited by 15 publications

(8 citation statements)

References 115 publications

(164 reference statements)

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“…In other regions of the brain, peptide release requires bursting or high-frequency activity. Furthermore, insulin secretion is controlled in pancreatic ␤-cells by ATP-sensitive K ϩ channels and voltage-dependent Ca 2ϩ channels (35). Differences in the molecular machinery of the secretory organelles may ensure differential release of the various secretory products.…”

Section: Discussionmentioning

confidence: 99%

Gene discovery in genetically labeled single dopaminergic neurons of the retina

Gustincich

Contini

Gariboldi

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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In the retina, dopamine plays a central role in neural adaptation to light. Progress in the study of dopaminergic amacrine (DA) cells has been limited because they are very few (450 in each mouse retina, 0.005% of retinal neurons). Here, we applied transgenic technology, single-cell global mRNA amplification, and cDNA microarray screening to identify transcripts present in DA cells. To profile gene expression in single neurons, we developed a method (SMART7) that combines a PCR-based initital step (switching mechanism at the 5 end of the RNA transcript or SMART) with T7 RNA polymerase amplification. Single-cell targets were synthesized from genetically labeled DA cells to screen the RIKEN 19k mouse cDNA microarrays. Seven hundred ninety-five transcripts were identified in DA cells at a high level of confidence, and expression of the most interesting genes was confirmed by immunocytochemistry. Twenty-one previously undescribed proteins were found in DA cells, including a chloride channel, receptors and other membrane glycoproteins, kinases, transcription factors, and secreted neuroactive molecules. Thirty-eight percent of transcripts were ESTs or coding for hypothetical proteins, suggesting that a large portion of the DA cell proteome is still uncharacterized. Because cryptochrome-1 mRNA was found in DA cells, immunocytochemistry was extended to other components of the circadian clock machinery. This analysis showed that DA cells contain the most common clock-related proteins.

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Section: Discussionmentioning

confidence: 99%

Gene discovery in genetically labeled single dopaminergic neurons of the retina

Gustincich

Contini

Gariboldi

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…In 1981, it was first described that glucose failed to promote insulin secretion in a concentration-dependent manner in isolated tissue from a child with hyperinsulinemia-induced hypoglycemia (Aynsley-Green, 1981;Dunne, 2000). The persistent hyperinsulinemia hypoglycemia of infancy, also named congenital hyperinsulinism (CHI), is a complex disorder composed of clinical, morphologic, and genetic changes (Shah et al, 2014).…”

Section: Pancreatic K Atp Channelopathiesmentioning

confidence: 99%

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

et al. 2016

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Pancreatic beta cells, unique cells that secrete insulin in response to an increase in glucose levels, play a significant role in glucose homeostasis. Glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells has been extensively explored. In this mechanism, glucose enters the cells and subsequently the metabolic cycle. During this process, the ATP/ADP ratio increases, leading to ATP-sensitive potassium (K ATP ) channel closure, which initiates depolarization that is also dependent on the activity of TRP nonselective ion channels. Depolarization leads to the opening of voltage-gated Na 1 channels (Nav) and subsequently voltage-dependent Ca 21 channels (Cav).The increase in intracellular Ca 21 triggers the exocytosis of insulin-containing vesicles. Thus, electrical activity of pancreatic beta cells plays a central role in GSIS. Moreover, many growth factors, incretins, neurotransmitters, and hormones can modulate GSIS, and the channels that participate in GSIS are highly regulated. In this review, we focus on the principal ionic channels (K ATP , Nav, and Cav channels) involved in GSIS and how classic and new proteins, hormones, and drugs regulate it. Moreover, we also discuss advances on how metabolic disorders such as metabolic syndrome and diabetes mellitus change channel activity leading to changes in insulin secretion.

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“…In mitochondria, Ac-CoA is catabolized, generating ATP from ADP. A high ATP-to-ADP ratio inhibits the ATP-sensitive potassium channel, which results in membrane depolarization (1). Depolarized ␤-cell membranes activate their voltage-dependent Ca 2ϩ channels (2), leading to an influx of Ca 2ϩ .…”

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confidence: 99%

Insulin Constitutively Secreted by β-Cells Is Necessary for Glucose-Stimulated Insulin Secretion

Srivastava

Goren

2003

Diabetes

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Four hypotheses have been posited on the role of insulin in glucose-stimulated insulin secretion; available evidence has supported insulin as being 1) essential, 2) a positive modulator, 3) a negative modulator, or 4) not necessary. Because circulating insulin levels in mice, before or after intraperitoneal glucose injection, are sufficient to elicit insulin responses in insulinsensitive tissues, it is likely that ␤-cell insulin receptors are continuously exposed to stimulating concentrations of insulin. To determine whether constitutively secreted insulin is necessary for glucose-stimulated insulin secretion, CD1 male mouse islets were incubated for 30 min at 4°C in the absence (control) or presence of anti-insulin (1 g/ml) or anti-IgG (1 g/ml). Then islets were exposed to 3, 11, or 25 mmol/l glucose or to 20 mmol/l arginine. Nontreated islets exhibited first-and second-phase glucose-stimulated insulin secretion. Control and anti-IgG-treated islets, after a 5-min lag phase, increased their insulin secretion in 25 mmol/l glucose. Anti-insulin؊treated islets secreted insulin at a basal rate in 3 or 25 mmol/l glucose buffers. Insulin secretion stimulated by 20 mmol/l arginine was the same in islets pretreated with either antibody and showed no lag phase. Taken together, these data suggest that constitutively secreted insulin is required and sufficient for ␤-cells to maintain sensitivity to glucose.

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Ions, genes and insulin release: from basic science to clinical disease Based on the 1998 R. D. Lawrence Lecture

Cited by 15 publications

References 115 publications

Gene discovery in genetically labeled single dopaminergic neurons of the retina

Gene discovery in genetically labeled single dopaminergic neurons of the retina

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

Insulin Constitutively Secreted by β-Cells Is Necessary for Glucose-Stimulated Insulin Secretion

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