Regulation of Human Pancreatic Secretion

Adler, Guido

doi:10.1159/000201523

Cited by 14 publications

(7 citation statements)

References 10 publications

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“…In rodents it appears that two mechanisms are likely involved, one indirect and one direct. The indirect mechanism involves the binding of CCK to CCK1 receptor expressed in afferent neurones that influence pancreatic secretion by way of a vagal-vagal loop with the final mediator being acetylcholine acting at m3 muscarinic cholinergic receptors (m3 AchR) (Owyang 1996;Adler 1997). This mechanism has also been reported to exist in man (Owyang 1996).…”

mentioning

confidence: 99%

“…However, the mechanisms involved in this response in man remain controversial (Niederau et al 1994;Owyang 1996;Adler 1997). Confusion has arisen due to basic differences between the mechanisms that exist in commonly utilized rodent animal models and those that exist in man.…”

mentioning

confidence: 99%

“…A major physiological function of cholecystokinin (CCK) in human physiology is the stimulation of pancreatic enzyme secretion, a phenomenon that has been known for nearly 60 years (Harper & Raper 1943). However, the mechanisms involved in this response in man remain controversial (Niederau et al 1994;Owyang 1996;Adler 1997). Confusion has arisen due to basic differences between the mechanisms that exist in commonly utilized rodent animal models and those that exist in man.…”

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confidence: 99%

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Human Pancreatic Acinar Cells Do Not Respond to Cholecystokinin

Simeone

et al. 2002

Pharmacology & Toxicology

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Pancreatic secretion can be influenced by cholecystokinin (CCK) either directly via actions on acinar cells or indirectly via actions on nerves. The presence and functional roles of CCK receptors on human pancreatic acinar cells remains unclear. In the current study human pancreatic acini were isolated and then treated with CCK-8, gastrin and/or carbachol. Functional parameters were measured including intracellular [Ca2π] and amylase secretion. It was observed that human acini did not respond to CCK agonists but did respond to carbachol with robust increases in functional parameters. Adenoviral-mediated gene transfer of CCK1 or CCK2 receptors to the human cells resulted in cell responses to CCK agonists. In order to determine the reason for the lack of responsiveness of the human acini, expression of receptor mRNAs was determined using quantitative RT-PCR and localized by in situ hybridization. mRNA levels for CCK1 receptors were ∂30 times lower than those of CCK2 receptors, which were ∂10 times lower than those of m3 Ach receptors as measured by quantitative PCR. Neither CCK1 nor CCK2 receptors were localized in adult human pancreas by in situ hybridization. These results indicate that human pancreatic acinar cells do not respond directly to CCK receptor activation and this is likely due to an insufficient level of receptor expression.

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Human Pancreatic Acinar Cells Do Not Respond to Cholecystokinin

Simeone

et al. 2002

Pharmacology & Toxicology

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“…While some studies have reported that these cells might lack functional CCK1 receptors [ 90 , 91 ], a more recent study has shown that physiological concentrations of CCK directly stimulate amylase release by isolated human pancreatic acinar cells [ 92 ]. Cerulein also signals by an indirect pathway, involving interaction with the CCK1 receptor expressed in afferent neurons that regulate pancreatic secretion via a vagal–vagal loop, with the final mediator being acetylcholine [ 93 , 94 ]. The human acinar cells used by Bhatia et al [ 58 ] were isolated as cell clusters, and therefore it is possible that the observed effects of cerulein in these cells may be indirect and therefore mediated by the afferent neurons present in the acini.…”

Section: Increased Pthrp Levels After Acinar Cell and Psc Injury Lmentioning

confidence: 99%

Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis

Falzon¹,

Bhatia²

2015

Cancers

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Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP) signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis) in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation.

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“…41 Secretin gene expression has been documented in the ileum and colon and immunoreactivity for the counterpart protein has been found in the central nervous system and gastric antral mucosa. 42 Secretin receptors are located in the stomach and pancreatic acini.…”

Section: Secretinmentioning

confidence: 99%

Control of Glucose Homeostasis by Incretin Hormones

Perfetti¹,

Brown²,

Velikina³

et al. 1999

Diabetes Technology & Therapeutics

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In humans as well as in other animal species, the ingestion of food provides the fundamental source of energy for various cellular activities. The intake of food and the ability of controlling the plasma levels of substrates for energy production involve complex mechanisms that ensure a constantly adequate supply of metabolites both in the fasting and in the fed state. A number of hormonal peptides released from the gastrointestinal (GI) tract in response to the ingestion of food have been shown to play a critical role in the postprandial control of glucose homeostasis. They are known to act through three main mechanisms of action. These include; (1) stimulation of insulin secretion of pancreatic islet (beta) cells; (2) inhibition of hepatic gluconeogenesis by suppression of glucagon secretion; and (3) inhibition of GI motility. While for some of these hormones all three mechanisms of action are utilized under physiological conditions, others preferentially use one or a combination of two mechanisms for lowering postprandial hyperglycemia. Although the term glucoincretins (or incretins, or insulinotropic hormones) etymologically only describes factors capable of inducing insulin secretion, it is more frequently used to identify a larger class of peptides that, rather than manifesting a specific mechanism of action (i.e., insulin secretion), share the ability of controlling glucose excursion in the fed state (with or without a direct insulinotropic effect). The latter more inclusive meaning, incretins, is used in this article. This review summarizes recent advances on synthesis, secretion, blood plasma patterns, and metabolism of some of the major GI regulatory peptides acting in the postprandial state.

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Regulation of Human Pancreatic Secretion

Cited by 14 publications

References 10 publications

Human Pancreatic Acinar Cells Do Not Respond to Cholecystokinin

Human Pancreatic Acinar Cells Do Not Respond to Cholecystokinin

Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis

Control of Glucose Homeostasis by Incretin Hormones

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