Cosecretion of amylin and insulin from isolated rat pancreas

Fehmann, Hans-Christoph; Weber, V.; Göke, Rüdiger; Göke, Burkhard; Arnold, R.

doi:10.1016/0014-5793(90)80210-a

Cited by 90 publications

(38 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, 80% of the protein in a vesicle is an equimolar mixture of insulin and C-peptide (22). The most likely proteinaceous interferent is amylin, which has been shown to be present at up to 10% of the level of insulin in a vesicle (23). As a disulfide-containing peptide, it is detectable at the electrode with a similar sensitivity to insulin.…”

Section: Methodsmentioning

confidence: 94%

Detection of exocytosis at individual pancreatic beta cells by amperometry at a chemically modified microelectrode.

Huang

Shen

Atkinson

et al. 1995

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

112

108

View full text Add to dashboard Cite

Amperometry at a carbon fiber microelectrode modified with a composite of ruthenium oxide and cyanoruthenate was used to monitor chemical secretions of single pancreatic .3 cells from rats and humans. When the insulin secretagogues glucose, tolbutamide, and K+ were applied to the cell, a-series of randomly occurring current spikes was observed. The current spikes were shown to be due to the detection of chemical substances secreted from the cell. Chromatography showed that the primary secreted substance detected by the electrode was insulin. The current spikes were strongly dependent on external Ca2+, had an average area that was independent of the stimulation method, and had an area distribution which corresponded to the distribution of vesicle sizes in f8 cells. It was concluded that the spikes were due to the detection of concentration pulses of insulin secreted by exocytosis.

show abstract

Section: Methodsmentioning

confidence: 94%

Detection of exocytosis at individual pancreatic beta cells by amperometry at a chemically modified microelectrode.

Huang

Shen

Atkinson

et al. 1995

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

112

108

View full text Add to dashboard Cite

show abstract

“…Another evidence for the activation of a pancreatic differentiation program in ES cells by following our protocol, is the up-regulation of insulin and IAPP, a peptide almost exclusively expressed in beta-cells and co-secreted with insulin (Fehmann et al, 1990). …”

mentioning

confidence: 80%

Embryonic stem cells differentiate into insulin-producing cells without selection of nestin-expressing cells

Błyszczuk¹,

Asbrand²,

Rozzo³

et al. 2004

Int. J. Dev. Biol.

101

View full text Add to dashboard Cite

“…β Cells are known to cosecrete with insulin a variety of substances that can act as agonists of GPCRs, for example, serotonin, nucleotides, amylin, or bivalent cations (41)(42)(43); in addition, they produce and release prostaglandins upon glucose stimulation (44). In order to investigate which of these mediators are able to potentiate β cell activation in a Gα q /Gα 11 -dependent manner, we studied calcium mobilization in isolated β cells at sub-threshold glucose levels ( Figure 5, C and D).…”

Section: Figurementioning

confidence: 99%

The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice

Sassmann¹,

Gier²,

Gröne³

et al. 2010

J. Clin. Invest.

View full text Add to dashboard Cite

A variety of neurotransmitters, gastrointestinal hormones, and metabolic signals are known to potentiate insulin secretion through GPCRs. We show here that β cell-specific inactivation of the genes encoding the G protein α-subunits Gα q and Gα 11 resulted in impaired glucose tolerance and insulin secretion in mice. Interestingly, the defects observed in Gα q /Gα 11 -deficient β cells were not restricted to loss of muscarinic or metabolic potentiation of insulin release; the response to glucose per se was also diminished. Electrophysiological recordings revealed that glucose-induced depolarization of isolated β cells was impaired in the absence of Gα q /Gα 11 , and closure of K ATP channels was inhibited. We provide evidence that this reduced excitability was due to a loss of β cell-autonomous potentiation of insulin secretion through factors cosecreted with insulin. We identified as autocrine mediators involved in this process extracellular nucleotides such as uridine diphosphate acting through the G q /G 11 -coupled P2Y6 receptor and extracellular calcium acting through the calciumsensing receptor. Thus, the G q /G 11 -mediated signaling pathway potentiates insulin secretion in response to glucose by integrating systemic as well as autocrine/paracrine mediators. IntroductionThe adequate secretion of insulin from pancreatic β cells is essential for the maintenance of normoglycemia; impaired insulin secretion results in diabetes mellitus with hyperglycemia, dyslipidemia, and consequent long-term tissue damage (1). The on-demand release of insulin from β cells is mainly regulated by blood glucose levels: high concentrations of glucose result in enhanced intracellular glucose metabolism with accumulation of ATP and consecutive closure of ATP-sensitive K + channels, leading to the opening of voltage-operated Ca 2+ channels and Ca 2+ -mediated exocytosis of insulin-containing vesicles (2, 3).While the ATP-dependent mechanism is clearly the master regulator of insulin release, various mediators potentiate insulin release in response to glucose. For example, gastrointestinal hormones such as glucose-dependent insulinotropic polypeptide (GIP) or glucagon-like peptide-1 (GLP-1) potentiate insulin secretion by activation of GPCRs, which signal through the G s family of heterotrimeric G proteins (4-6). The potentiating effect of G s on glucose-induced insulin release depends on activation of adenylyl cyclase and consecutive phosphorylation of voltage-operated Ca 2+ channels (7, 8) or opening of nonselective cation channels (9).Another important group of modulators are neurotransmitters and neuropeptides (10, 11), most prominent among them being the neurotransmitter acetylcholine, which is released from vagal nerve terminals and potentiates insulin secretion through the muscarinic receptor subtype M 3 (12)(13)(14)(15). In contrast to the receptors for GIP and GLP-1, the M 3 receptor does not elicit G smediated adenylyl cyclase activation, but was shown to signal through the G q /G 11 family of heterotrimeric G proteins. Th...

show abstract

Cosecretion of amylin and insulin from isolated rat pancreas

Cited by 90 publications

References 14 publications

Detection of exocytosis at individual pancreatic beta cells by amperometry at a chemically modified microelectrode.

Detection of exocytosis at individual pancreatic beta cells by amperometry at a chemically modified microelectrode.

Embryonic stem cells differentiate into insulin-producing cells without selection of nestin-expressing cells

The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice

Contact Info

Product

Resources

About