The Local Paracrine Actions of the Pancreatic α-Cell

Rodriguez-Diaz, Rayner; Tamayo, Alejandro; Hara, Manami; Caicedo, Alejandro

doi:10.2337/dbi19-0002

Cited by 49 publications

(38 citation statements)

References 94 publications

(123 reference statements)

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“…Like the beta cell, the alpha cell contains and releases, a number of factors besides its major hormonal product, glucagon, that can have both autocrine and paracrine signalling properties [3].…”

Section: Factors Released By the Alpha Cellmentioning

confidence: 99%

“…GLP-1 can be produced in two isoforms: GLP-1(7-37) (corresponding to amino acids 78-108 of the proglucagon peptide) and GLP-1(7-36NH 2 ) (78-107NH 2 ); the second isoform is generated by α-amidation of the carboxyl-terminal arginine residue. This figure is available as part of a downloadable slideset which functions as a paracrine signal sensitising the beta cell to the prevailing glucose concentration [3,23].…”

Section: Factors Released By the Alpha Cellmentioning

confidence: 99%

“…islets from different parts of the rat pancreas, show improved GSIS compared with islets with a lower alpha cell content, a difference that could be eliminated by the addition of exogenous glucagon [31]. Mechanistically, the positive effect of glucagon on beta cell function is achieved by glucagon binding to the glucagon receptor, a G-protein-coupled receptor (GPCR) that is expressed in beta cells, and the activation of the cAMP/PKA/EPAC system [3,12,26,27,32]. The importance of glucagon receptor signalling for beta cell function was confirmed by a positive effect of beta cell specific overexpression of the glucagon receptor [33].…”

Section: Effects Of Glucagon On the Pancreatic Beta Cellmentioning

confidence: 99%

“…To confirm the importance of acetylcholine as a (c, d). The illustration is based on observations published in [3,35,[45][46][47][48][49][50][51]. This figure is available as part of a downloadable slideset paracrine signal, islets were challenged with an experimental protocol that alternately stimulated alpha and beta cells in the presence of modulators of the acetylcholine signalling system.…”

Section: Alpha Cells As a Source Of Cholinergic Signals In Human Isletsmentioning

confidence: 99%

“…One interesting and maybe more philosophical question to consider is why these two counteracting hormones are produced in such close proximity to each other. Mathematical modelling suggests that a system in which the products of one partner, like the glucagon produced by the pancreatic alpha cell, have a stimulatory effect on its counterpart, while the other partner’s products, like the insulin secreted by the beta cell, have inhibitory effects, enables active regulation to maintain stable levels, something that is indeed mandatory for the control of blood glucose concentration [ 1 – 3 ]. It is therefore of interest to explore the mechanisms that are involved in the interplay between alpha and beta cells.…”

Section: Introductionmentioning

confidence: 99%

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Alpha cell regulation of beta cell function

2020

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The islet of Langerhans is a complex endocrine micro-organ consisting of a multitude of endocrine and non-endocrine cell types. The two most abundant and prominent endocrine cell types, the beta and the alpha cells, are essential for the maintenance of blood glucose homeostasis. While the beta cell produces insulin, the only blood glucose-lowering hormone of the body, the alpha cell releases glucagon, which elevates blood glucose. Under physiological conditions, these two cell types affect each other in a paracrine manner. While the release products of the beta cell inhibit alpha cell function, the alpha cell releases factors that are stimulatory for beta cell function and increase glucose-stimulated insulin secretion. The aim of this review is to provide a comprehensive overview of recent research into the regulation of beta cell function by alpha cells, focusing on the effect of alpha cell-secreted factors, such as glucagon and acetylcholine. The consequences of differences in islet architecture between species on the interplay between alpha and beta cells is also discussed. Finally, we give a perspective on the possibility of using an in vivo imaging approach to study the interactions between human alpha and beta cells under in vivo conditions.

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Section: Factors Released By the Alpha Cellmentioning

confidence: 99%

Section: Factors Released By the Alpha Cellmentioning

confidence: 99%

Section: Effects Of Glucagon On the Pancreatic Beta Cellmentioning

confidence: 99%

Section: Alpha Cells As a Source Of Cholinergic Signals In Human Isletsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alpha cell regulation of beta cell function

2020

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Intercellular Communication in the Islet of Langerhans in Health and Disease

Chung

Piston

2021

Comprehensive Physiology

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Blood glucose homeostasis requires proper function of pancreatic islets, which secrete insulin, glucagon, and somatostatin from the β-, α-, and δ-cells, respectively. Each islet cell type is equipped with intrinsic mechanisms for glucose sensing and secretory actions, but these intrinsic mechanisms alone cannot explain the observed secretory profiles from intact islets. Regulation of secretion involves interconnected mechanisms among and between islet cell types. Islet cells lose their normal functional signatures and secretory behaviors upon dispersal as compared to intact islets and in vivo. In dispersed islet cells, the glucose response of insulin secretion is attenuated from that seen from whole islets, coordinated oscillations in membrane potential and intracellular Ca 2+ activity, as well as the two-phase insulin secretion profile, are missing, and glucagon secretion displays higher basal secretion profile and a reverse glucose-dependent response from that of intact islets. These observations highlight the critical roles of intercellular communication within the pancreatic islet, and how these communication pathways are crucial for proper hormonal and nonhormonal secretion and glucose homeostasis. Further, misregulated secretions of islet secretory products that arise from defective intercellular islet communication are implicated in diabetes. Intercellular communication within the islet environment comprises multiple mechanisms, including electrical synapses from gap junctional coupling, paracrine interactions among neighboring cells, and direct cell-to-cell contacts in the form of juxtacrine signaling. In this article, we describe the various mechanisms that contribute to proper islet function for each islet cell type and how intercellular islet communications are coordinated among the same and different islet cell types.

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Noncanonical Regulation of cAMP‐Dependent Insulin Secretion and Its Implications in Type 2 Diabetes

Ramanadham

Turk

Bhatnagar

2023

Comprehensive Physiology

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Impaired glucose tolerance (IGT) and β-cell dysfunction in insulin resistance associated with obesity lead to type 2 diabetes (T2D). Glucose-stimulated insulin secretion (GSIS) from β-cells occurs via a canonical pathway that involves glucose metabolism, ATP generation, inactivation of K ATP channels, plasma membrane depolarization, and increases in cytosolic concentrations of [Ca 2+ ] c . However, optimal insulin secretion requires amplification of GSIS by increases in cyclic adenosine monophosphate (cAMP) signaling. The cAMP effectors protein kinase A (PKA) and exchange factor activated by cyclic-AMP (Epac) regulate membrane depolarization, gene expression, and trafficking and fusion of insulin granules to the plasma membrane for amplifying GSIS. The widely recognized lipid signaling generated within β-cells by the β-isoform of Ca 2+ -independent phospholipase A 2 enzyme (iPLA 2 β) participates in cAMP-stimulated insulin secretion (cSIS). Recent work has identified the role of a G-protein coupled receptor (GPCR) activated signaling by the complement 1q like-3 (C1ql3) secreted protein in inhibiting cSIS. In the IGT state, cSIS is attenuated, and the β-cell function is reduced. Interestingly, while β-cell-specific deletion of iPLA 2 β reduces cAMP-mediated amplification of GSIS, the loss of iPLA 2 β in macrophages (MØ) confers protection against the development of glucose intolerance associated with diet-induced obesity (DIO). In this article, we discuss canonical (glucose and cAMP) and novel noncanonical (iPLA 2 β and C1ql3) pathways and how they may affect β-cell (dys)function in the context of impaired glucose intolerance associated with obesity and T2D. In conclusion, we provide a perspective that in IGT states, targeting noncanonical pathways along with canonical pathways could be a more comprehensive approach for restoring β-cell function in T2D.

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The Local Paracrine Actions of the Pancreatic α-Cell

Cited by 49 publications

References 94 publications

Alpha cell regulation of beta cell function

Alpha cell regulation of beta cell function

Intercellular Communication in the Islet of Langerhans in Health and Disease

Noncanonical Regulation of cAMP‐Dependent Insulin Secretion and Its Implications in Type 2 Diabetes

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