2014
DOI: 10.1111/dom.12301
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Effect of hyperglycaemia on muscarinic M3 receptor expression and secretory sensitivity to cholinergic receptor activation in islets

Abstract: Cholinergic regulation of insulin release is impaired in three experimental islet models of hyperglycaemia consistent with reduced expression of M3 receptors. Our data suggest that the receptor downregulation is a PKC- and PI3K-independent consequence of the hyperglycaemic environment, and they imply that M3 receptors could be potential targets in the treatment of type 2 diabetes.

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Cited by 13 publications
(12 citation statements)
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References 48 publications
(78 reference statements)
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“…Some researchers are of the view that hyperglycemia and diabetes caused by quetiapine therapy are primarily the result of M 3 receptor antagonism. 22 ) So it would appear that while norquetiapine is responsible for therapeutic effects it may also be to blame for quetiapine’s adverse effects.…”
Section: Main Subjectsmentioning
confidence: 99%
“…Some researchers are of the view that hyperglycemia and diabetes caused by quetiapine therapy are primarily the result of M 3 receptor antagonism. 22 ) So it would appear that while norquetiapine is responsible for therapeutic effects it may also be to blame for quetiapine’s adverse effects.…”
Section: Main Subjectsmentioning
confidence: 99%
“…To determine the signalling cascades, islets were treated with various intracellular inhibitors, pertussis toxin (1 ng/mL), U73122 (5 μM), Go6983 (1 μM), gallein (10 μM) or MEK inhibitor U0126 (5 μM), in the absence or presence of cytokines. PKC was depleted using PMA (200 nM) for 21 hours prior to treatment with cytokines . TUNEL staining was used to localize the anti‐apoptotic effect of 1 nM [Leu 31 Pro 34 ]‐NPY on beta‐cells.…”
Section: Methodsmentioning
confidence: 99%
“…Mouse islets were isolated from male CD1 mice aged 8–12 weeks (Charles River Laboratories, Margate, UK) by collagenase digestion (1 mg/mL; type XI; Sigma‐Aldrich, Poole, UK) and separated on a histopaque gradient (Histopaque 1077; Sigma‐Aldrich) . Human islets were obtained from the pancreata of non‐diabetic heart‐beating donors with appropriate ethical approval .…”
Section: Methodsmentioning
confidence: 99%
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“…Interestingly, M3 receptor expression is down regulated by high glucose treatment in mouse and human islets, thus suggesting that impaired glucose sensing and insulin secretion observed in diabetes may also be due to alteration of paracrine signaling systems (Hauge‐Evans et al, ).…”
Section: Acetylcholinementioning
confidence: 99%