Muscarinic M1 and M3 Receptor Binding Alterations in Pancreas During Pancreatic Regeneration of Young Rats

Renuka, T. R.; Savitha, B.; Paulose, C S

doi:10.1080/07435800500406163

Cited by 15 publications

(12 citation statements)

References 36 publications

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“…Thus, a) Cch increases [Ca 2C ]i, MAPK1 phosphorylation, protein synthesis, and cell proliferation in a human breast cancer cell line (Jimenez & Montiel 2005); b) M3 muscarinic cholinergic receptors activate p70S6K1 via PI3K signaling pathway in astrocytoma cells (Tang et al 2003, Batty et al 2004); c) a novel pathway of acetylcholine-stimulated activation of eNOS, involving the JAK2/IRS-1/PI3K/ Akt1 pathway, has recently been reported in aorta of obese rats that are simultaneously resistant to insulin and Cch (Zecchin et al 2007); and d) islet M1 and M3 muscarinic receptor expression is increased during islet cell regeneration (Renuka et al 2005). The increased expression of such receptors is associated with an increase in insulin secretion that, in turn, might modulate b-cell growth and differentiation via IRS2 activation (Velloso et al 1995).…”

Section: Effects Of Cch On Insulin Release From Ingap-pp-cultured Andmentioning

confidence: 99%

Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: involvement of the cholinergic pathway

Barbosa¹,

Bordin²,

Anhê³

et al. 2008

Journal of Endocrinology

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Islet neogenesis associated protein (INGAP) increases islet mass and insulin secretion in neonatal and adult rat islets. In the present study, we measured the short-and long-term effects of INGAP-PP (a pentadecapeptide having the 104-118 amino acid sequence of INGAP) upon islet protein expression and phosphorylation of components of the PI3K, MAPK and cholinergic pathways, and on insulin secretion. Short-term exposure of neonatal islets to INGAP-PP (90 s, 5, 15, and 30 min) significantly increased Akt1 -Ser473 and MAPK3/1 -Thr202/Tyr204 phosphorylation and INGAP-PP also acutely increased insulin secretion from islets perifused with 2 and 20 mM glucose. Islets cultured for 4 days in the presence of INGAP-PP showed an increased expression of Akt1, Frap1, and Mapk1 mRNAs as well as of the muscarinic M3 receptor subtype, and phospholipase C (PLC)-b2 proteins. These islets also showed increased Akt1 and MAPK3/1 protein phosphorylation. Brief exposure of INGAP-PP-treated islets to carbachol (Cch) significantly increased P70S6K -Thr389 and MAPK3/1 phosphorylation and these islets released more insulin when challenged with Cch that was prevented by the M3 receptor antagonist 4-DAMP, in a concentration-dependent manner. In conclusion, these data indicate that short-and long-term exposure to INGAP-PP significantly affects the expression and the phosphorylation of proteins involved in islet PI3K and MAPK signaling pathways. The observations of INGAPP-PP-stimulated up-regulation of cholinergic M3 receptors and PLC-b2 proteins, enhanced P70S6K and MAPK3/1 phosphorylation and Cch-induced insulin secretion suggest a participation of the cholinergic pathway in INGAP-PP-mediated effects.

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Section: Effects Of Cch On Insulin Release From Ingap-pp-cultured Andmentioning

confidence: 99%

Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: involvement of the cholinergic pathway

Barbosa¹,

Bordin²,

Anhê³

et al. 2008

Journal of Endocrinology

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“…The insulinotropic ACh response in pancreatic islets is mostly generated by M 3 mAChR and to a lesser degree by M 1 mAChR [10,12]. These receptors are coupled to G protein subtype Gq/ 11 [13], which activates phospholipase C (PLC), thus cleaving phosphatidylinositol-4, 5-bisphosphate (PIP) into diacylglycerol (DAG) and inositol 1, 4, 5 -triphosphate (IP3).…”

Section: Introductionmentioning

confidence: 99%

Insulin Oversecretion in MSG-Obese Rats is Related to Alterations in Cholinergic Muscarinic Receptor Subtypes in Pancreatic Islets

Miranda

Agostinho

Trevenzoli

et al. 2014

Cell Physiol Biochem

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Background/ Aims: Impaired pancreatic beta cell function and insulin secretion/action are a link between obesity and type 2 diabetes, which are worldwide public health burdens. We aimed to characterize the muscarinic acetylcholine receptor (mAChR) M₁-M₄ subtypes in isolated pancreatic islets from pre-diabetic obese rats that had been treated neonatally with monosodium L-glutamate (MSG). Methods: At 90 days of age, both the MSG and the control groups underwent biometric and biochemical evaluation. Anti-muscarinic drugs were used to study mAChR function either in vivo or in vitro. Results: The results demonstrated that atropine treatment reduced insulin secretion in the MSG-treated and control groups, whereas treatment with an M₂mAChR-selective antagonist increased secretion. Moreover, the insulinostatic effect of an M₃mAChR-selective antagonist was significantly higher in the MSG-treated group. M₁mAChR and M₃mAChR expression was increased in the MSG-obese group by 55% and 73%, respectively. In contrast, M₂mAChR expression decreased by 25% in the MSG group, whereas M₄mAChR expression was unchanged. Conclusions: Functional changes in and altered content of the mAChR (M₁-M₄) subtypes are pivotal to the demand for high pancreatic beta cell insulin secretion in MSG-obese rats, which is directly associated with vagal hyperactivity and peripheral insulin resistance.

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“…Importantly, the upregulation of these receptors was temporally correlated with a transient DNA synthesis in islets. These investigators also mapped the centers of the brainstem that are activated upon pancreatic regeneration following partial pancreatectomy (38).…”

Section: E790mentioning

confidence: 99%

Vagal control of pancreatic β-cell proliferation

Lausier

Diaz

Roskens

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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The physiological mechanisms that preserve pancreatic ␤-cell mass (BCM) are not fully understood. Although the regulation of islet function by the autonomic nervous system (ANS) is well established, its potential roles in BCM homeostasis and compensatory growth have not been adequately explored. The parasympathetic vagal branch of the ANS serves to facilitate gastrointestinal function, metabolism, and pancreatic islet regulation of glucose homeostasis, including insulin secretion. Given the functional importance of the vagus nerve and its branches to the liver, gut, and pancreas in control of digestion, motility, feeding behavior, and glucose metabolism, it may also play a role in BCM regulation. We have begun to examine the potential roles of the parasympathetic nervous system in short-term BCM maintenance by performing a selective bilateral celiac branch-vagus nerve transection (CVX) in normal Sprague-Dawley rats. CVX resulted in no detectable effects on basic metabolic parameters or food intake through 1 wk postsurgery. Although there were no differences in BCM or apoptosis in this 1-wk time frame, ␤-cell proliferation was reduced 50% in the CVX rats, correlating with a marked reduction in activated protein kinase B/Akt. Unexpectedly, acinar proliferation was increased 50% in these rats. These data suggest that the ANS, via the vagus nerve, contributes to the regulation of BCM maintenance at the level of cell proliferation and may also mediate the drive for enhanced growth under physiological conditions when insulin requirements have increased. Furthermore, the disparate effects of CVX on ␤-cell and acinar cells suggest that the endocrine and exocrine pancreas respond to different neural signals in regard to mass homeostasis.␤-cell mass; celiac vagotomy THE PANCREATIC ␤-CELL HAS A TREMENDOUS CAPACITY to functionally compensate in response to physiological and pathophysiological changes in tissue insulin demands. A key feature of this adaptive response is the ability of the ␤-cell mass (BCM) to be dynamically regulated. For instance, BCM is normally maintained proportionally to body size. It increases during obesity and pregnancy (5,14,20) and regresses postpartum (42) to adjust to physiological insulin requirements. The steady-state BCM is determined by new cell recruitment by hyperplasia of existing cells and neogenesis from pancreatic epithelial progenitors, apoptotic death and clearance, and hypertrophy (5). The relative importance of each of these different processes is largely unknown and depends on the model under study; nonetheless, several recent reports suggest that proliferation from preexisting ␤-cells predominates in mice (10,11,29,30).The interplay of nutrients, growth factors, and hormones is known to impact ␤-cell growth; however, the influence of the nervous system on ␤-cell growth processes has been understudied. There are a handful of reports highlighting the importance of the vagus efferents in ␤-cell proliferation. A transient decrease in ␤-cell proliferation was observed in ob/ob mice, bu...

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Muscarinic M1 and M3 Receptor Binding Alterations in Pancreas During Pancreatic Regeneration of Young Rats

Cited by 15 publications

References 36 publications

Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: involvement of the cholinergic pathway

Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: involvement of the cholinergic pathway

Insulin Oversecretion in MSG-Obese Rats is Related to Alterations in Cholinergic Muscarinic Receptor Subtypes in Pancreatic Islets

Vagal control of pancreatic β-cell proliferation

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