Alpha-cells: Its Role as the Islet Harmonizer

Nabil Kamal Elnaggar; Mohamed Nabil Elnaggar

doi:doi:10.11648/j.ijde.20190404.13

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Alpha-cells: Its Role as the Islet Harmonizer

Nabil Kamal Elnaggar, Mohamed Nabil Elnaggar

Published in International Journal of Diabetes and Endocrinology (Volume 4, Issue 4)

Received: 16 October 2019 Accepted: 18 November 2019 Published: 27 November 2019

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Abstract

It has long been thought that the alpha cells and its secretory products play an important role solely in maintaining euglycemia and preventing hypoglycemia through a contradictory action to the B cell’s insulin. The α-cell function is tightly regulated by various physiological inputs including systemic energy status, central and autonomic nervous systems, and the endocrine system. It is also an important amino acid sensor, glucagon blockade suppresses hepatic amino acid catabolism and increases the serum amino acid level. In addition to those controllers, the intra-islet microenvironment, where α-cells are located, has been recently revealed to be important in the regulation of the various cellular secretory functions including the overlapping of glucagon and insulin secretion through a precise cell-cell crosstalk. Paracrine interactions between pancreatic islet cells have been proposed as a mechanism to regulate hormone secretion and glucose homeostasis, alpha and B cells are closely positioned on the sides of their blood supply where acetylcholine acts as the paracrine communicator of signals inside the islets. Recently, it has been demonstrated that blocking acetylcholine esterase increases insulin secretion. Moreover, it has also been suggested that glucagon is not exclusively a counter-regulatory hormone that elevates blood glucose levels, in contrast it can cause hypoglycemia conditioned by the presence of intact B cells and a functional GLP-1R (glucagon-like peptide 1 receptor). These data argue for glucagon agonism in modern management of T2DM. Alpha-cells also, have been shown to be able to trans-differentiate into β-cells only in the presence of insulin-positive cells with α-cell origin in the lineage tracing analyses, confirming the role of α-cells as a source of β-cell regeneration. The article reviews the updated knowledge about the functions of the alpha-cells and its role in the paracrine control of islet cell secretions and the future therapeutic potentials.

Published in	International Journal of Diabetes and Endocrinology (Volume 4, Issue 4) This article belongs to the Special Issue Hypoglycemia in Diabetes
DOI	10.11648/j.ijde.20190404.13
Page(s)	104-107
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2019. Published by Science Publishing Group

Keywords

Pancreatic Islet Cells, B Cells, Alpha Cells, Glucagon, GIP (Glucose-dependent Insulinotropic Polypeptide), GLP-1 (Glucagon-like Peptide 1)

References

[1]	Kawamori D. Exploring molecular mechanisms underlying a- and b-cell dysfunction in diabetes. Diabetol Int 2017; 8: 248–256.
[2]	Stanojevic V, Habener JF. Evolving function and potential of pancreatic alpha cells. Best Pract Res Clin Endocrinol Metab 2015; 29: 859–871.
[3]	Xiaoqing Dai, et al. Pancreatic Alpha-Cell Function and Identity in Human T2D. Diabetes 2018 Jul; 67 (Supplement 1): https://doi.org/10.2337/db18-315-LB
[4]	Kawamori D. Alpha the versatile: Guardians of the islets. J Diabetes Investig. 2019 Jan; 10 (1): 26-28. doi: 10.1111/jdi.12875. Epub 2018 Jul 25.
[5]	Lam CJ, Cox AR, Jacobson DR, et al. Highly proliferative alpha-cellrelated islet endocrine cells in human pancreata. Diabetes 2018; 67: 674–686.
[6]	Takahashi N et al. Contribution of pancreatic a-cell function to insulin sensitivity and glycemic variability in patients with type 1 diabetes. J Diabetes Investig Vol. 10 No. 3 May 2019.
[7]	Bertuzzi F, Berra C, Socci C, Davalli AM, Calori G, Freschi M, Piemonti L, De Nittis P, Pozza G, Pontiroli AE. Glucagon improves insulin secretion from pig islets in vitro. J Endocrinol. 1995; 147: 87–93. [PubMed: 7490541].
[8]	Huypens P, Ling Z, Pipeleers D, Schuit F. Glucagon receptors on human islet cells contribute to glucose competence of insulin release. Diabetologia. 2000; 43: 1012–1019. [PubMed: 10990079].
[9]	Pipeleers D, Veld PI, Maes E, and Van De Winkel M. Glucose-induced insulin release depends on functional cooperation between islet cells. Proc Natl Acad Sci U S A. 1982; 79: 7322–7325. [PubMed: 6760195]
[10]	Samols E, Marri G, Marks V. Promotion of insulin secretion by glucagon. Lancet. 1965; 2: 415–416. [PubMed: 14346763]
[11]	Rodriguez-Diaz R et al., paracrine interactions within the pancreatic islet determine the glycemic set point. Cell Metab. 2018 March 06; 27 (3): 549–558.e4. doi: 10.1016/j.
[12]	Holst JJ. The physiology of glucagon-like peptide 1. Pysiol Rev. 2007 Oct; 87 (4): 1409-39.
[13]	Vishal Gupta. Glucaon-like peptide 1 analogues: An overview. Indian J Endocrinol Metab. 2013 May-Jun; 17 (3): 413-421.
[14]	Prashant Nadkarmi, Oleg G. Chepurny, and George G. Holz. Regulation of Glucose Homeostasis by GLP-1. Prog Mol Biol Trans Sci. 2014; 121: 23-65.
[15]	Megan E. Capozzi, 1 Richard D. DiMarchi, Matthias H. Tschop, BrianFinan, and Jonathan E. Campbell. Targeting the Incretin/Glucagon System WithTriagonists to Treat Diabetes. Endocrine Reviews, October 2018, 39 (5): 719–738.

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APA Style

Nabil Kamal Elnaggar, Mohamed Nabil Elnaggar. (2019). Alpha-cells: Its Role as the Islet Harmonizer. International Journal of Diabetes and Endocrinology, 4(4), 104-107. https://doi.org/10.11648/j.ijde.20190404.13

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ACS Style

Nabil Kamal Elnaggar; Mohamed Nabil Elnaggar. Alpha-cells: Its Role as the Islet Harmonizer. Int. J. Diabetes Endocrinol. 2019, 4(4), 104-107. doi: 10.11648/j.ijde.20190404.13

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AMA Style

Nabil Kamal Elnaggar, Mohamed Nabil Elnaggar. Alpha-cells: Its Role as the Islet Harmonizer. Int J Diabetes Endocrinol. 2019;4(4):104-107. doi: 10.11648/j.ijde.20190404.13

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@article{10.11648/j.ijde.20190404.13,
  author = {Nabil Kamal Elnaggar and Mohamed Nabil Elnaggar},
  title = {Alpha-cells: Its Role as the Islet Harmonizer},
  journal = {International Journal of Diabetes and Endocrinology},
  volume = {4},
  number = {4},
  pages = {104-107},
  doi = {10.11648/j.ijde.20190404.13},
  url = {https://doi.org/10.11648/j.ijde.20190404.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijde.20190404.13},
  abstract = {It has long been thought that the alpha cells and its secretory products play an important role solely in maintaining euglycemia and preventing hypoglycemia through a contradictory action to the B cell’s insulin. The α-cell function is tightly regulated by various physiological inputs including systemic energy status, central and autonomic nervous systems, and the endocrine system. It is also an important amino acid sensor, glucagon blockade suppresses hepatic amino acid catabolism and increases the serum amino acid level. In addition to those controllers, the intra-islet microenvironment, where α-cells are located, has been recently revealed to be important in the regulation of the various cellular secretory functions including the overlapping of glucagon and insulin secretion through a precise cell-cell crosstalk. Paracrine interactions between pancreatic islet cells have been proposed as a mechanism to regulate hormone secretion and glucose homeostasis, alpha and B cells are closely positioned on the sides of their blood supply where acetylcholine acts as the paracrine communicator of signals inside the islets. Recently, it has been demonstrated that blocking acetylcholine esterase increases insulin secretion. Moreover, it has also been suggested that glucagon is not exclusively a counter-regulatory hormone that elevates blood glucose levels, in contrast it can cause hypoglycemia conditioned by the presence of intact B cells and a functional GLP-1R (glucagon-like peptide 1 receptor). These data argue for glucagon agonism in modern management of T2DM. Alpha-cells also, have been shown to be able to trans-differentiate into β-cells only in the presence of insulin-positive cells with α-cell origin in the lineage tracing analyses, confirming the role of α-cells as a source of β-cell regeneration. The article reviews the updated knowledge about the functions of the alpha-cells and its role in the paracrine control of islet cell secretions and the future therapeutic potentials.},
 year = {2019}
}

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TY  - JOUR
T1  - Alpha-cells: Its Role as the Islet Harmonizer
AU  - Nabil Kamal Elnaggar
AU  - Mohamed Nabil Elnaggar
Y1  - 2019/11/27
PY  - 2019
N1  - https://doi.org/10.11648/j.ijde.20190404.13
DO  - 10.11648/j.ijde.20190404.13
T2  - International Journal of Diabetes and Endocrinology
JF  - International Journal of Diabetes and Endocrinology
JO  - International Journal of Diabetes and Endocrinology
SP  - 104
EP  - 107
PB  - Science Publishing Group
SN  - 2640-1371
UR  - https://doi.org/10.11648/j.ijde.20190404.13
AB  - It has long been thought that the alpha cells and its secretory products play an important role solely in maintaining euglycemia and preventing hypoglycemia through a contradictory action to the B cell’s insulin. The α-cell function is tightly regulated by various physiological inputs including systemic energy status, central and autonomic nervous systems, and the endocrine system. It is also an important amino acid sensor, glucagon blockade suppresses hepatic amino acid catabolism and increases the serum amino acid level. In addition to those controllers, the intra-islet microenvironment, where α-cells are located, has been recently revealed to be important in the regulation of the various cellular secretory functions including the overlapping of glucagon and insulin secretion through a precise cell-cell crosstalk. Paracrine interactions between pancreatic islet cells have been proposed as a mechanism to regulate hormone secretion and glucose homeostasis, alpha and B cells are closely positioned on the sides of their blood supply where acetylcholine acts as the paracrine communicator of signals inside the islets. Recently, it has been demonstrated that blocking acetylcholine esterase increases insulin secretion. Moreover, it has also been suggested that glucagon is not exclusively a counter-regulatory hormone that elevates blood glucose levels, in contrast it can cause hypoglycemia conditioned by the presence of intact B cells and a functional GLP-1R (glucagon-like peptide 1 receptor). These data argue for glucagon agonism in modern management of T2DM. Alpha-cells also, have been shown to be able to trans-differentiate into β-cells only in the presence of insulin-positive cells with α-cell origin in the lineage tracing analyses, confirming the role of α-cells as a source of β-cell regeneration. The article reviews the updated knowledge about the functions of the alpha-cells and its role in the paracrine control of islet cell secretions and the future therapeutic potentials.
VL  - 4
IS  - 4
ER  -

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Author Information

Nabil Kamal Elnaggar

Diabetes, Obesity and Endocrinology Center, HaiAljamea Hospital, Jeddah, Kingdom of Saudi Arabia
Mohamed Nabil Elnaggar

Department of Endocrinology, Diabetes & Metabolism, University Hospitals of Morecambe Bay NHS Foundation Trust, Lancaster, United Kingdom

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APA Style

Nabil Kamal Elnaggar, Mohamed Nabil Elnaggar. (2019). Alpha-cells: Its Role as the Islet Harmonizer. International Journal of Diabetes and Endocrinology, 4(4), 104-107. https://doi.org/10.11648/j.ijde.20190404.13

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ACS Style

Nabil Kamal Elnaggar; Mohamed Nabil Elnaggar. Alpha-cells: Its Role as the Islet Harmonizer. Int. J. Diabetes Endocrinol. 2019, 4(4), 104-107. doi: 10.11648/j.ijde.20190404.13

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AMA Style

Nabil Kamal Elnaggar, Mohamed Nabil Elnaggar. Alpha-cells: Its Role as the Islet Harmonizer. Int J Diabetes Endocrinol. 2019;4(4):104-107. doi: 10.11648/j.ijde.20190404.13

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@article{10.11648/j.ijde.20190404.13,
  author = {Nabil Kamal Elnaggar and Mohamed Nabil Elnaggar},
  title = {Alpha-cells: Its Role as the Islet Harmonizer},
  journal = {International Journal of Diabetes and Endocrinology},
  volume = {4},
  number = {4},
  pages = {104-107},
  doi = {10.11648/j.ijde.20190404.13},
  url = {https://doi.org/10.11648/j.ijde.20190404.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijde.20190404.13},
  abstract = {It has long been thought that the alpha cells and its secretory products play an important role solely in maintaining euglycemia and preventing hypoglycemia through a contradictory action to the B cell’s insulin. The α-cell function is tightly regulated by various physiological inputs including systemic energy status, central and autonomic nervous systems, and the endocrine system. It is also an important amino acid sensor, glucagon blockade suppresses hepatic amino acid catabolism and increases the serum amino acid level. In addition to those controllers, the intra-islet microenvironment, where α-cells are located, has been recently revealed to be important in the regulation of the various cellular secretory functions including the overlapping of glucagon and insulin secretion through a precise cell-cell crosstalk. Paracrine interactions between pancreatic islet cells have been proposed as a mechanism to regulate hormone secretion and glucose homeostasis, alpha and B cells are closely positioned on the sides of their blood supply where acetylcholine acts as the paracrine communicator of signals inside the islets. Recently, it has been demonstrated that blocking acetylcholine esterase increases insulin secretion. Moreover, it has also been suggested that glucagon is not exclusively a counter-regulatory hormone that elevates blood glucose levels, in contrast it can cause hypoglycemia conditioned by the presence of intact B cells and a functional GLP-1R (glucagon-like peptide 1 receptor). These data argue for glucagon agonism in modern management of T2DM. Alpha-cells also, have been shown to be able to trans-differentiate into β-cells only in the presence of insulin-positive cells with α-cell origin in the lineage tracing analyses, confirming the role of α-cells as a source of β-cell regeneration. The article reviews the updated knowledge about the functions of the alpha-cells and its role in the paracrine control of islet cell secretions and the future therapeutic potentials.},
 year = {2019}
}

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TY  - JOUR
T1  - Alpha-cells: Its Role as the Islet Harmonizer
AU  - Nabil Kamal Elnaggar
AU  - Mohamed Nabil Elnaggar
Y1  - 2019/11/27
PY  - 2019
N1  - https://doi.org/10.11648/j.ijde.20190404.13
DO  - 10.11648/j.ijde.20190404.13
T2  - International Journal of Diabetes and Endocrinology
JF  - International Journal of Diabetes and Endocrinology
JO  - International Journal of Diabetes and Endocrinology
SP  - 104
EP  - 107
PB  - Science Publishing Group
SN  - 2640-1371
UR  - https://doi.org/10.11648/j.ijde.20190404.13
AB  - It has long been thought that the alpha cells and its secretory products play an important role solely in maintaining euglycemia and preventing hypoglycemia through a contradictory action to the B cell’s insulin. The α-cell function is tightly regulated by various physiological inputs including systemic energy status, central and autonomic nervous systems, and the endocrine system. It is also an important amino acid sensor, glucagon blockade suppresses hepatic amino acid catabolism and increases the serum amino acid level. In addition to those controllers, the intra-islet microenvironment, where α-cells are located, has been recently revealed to be important in the regulation of the various cellular secretory functions including the overlapping of glucagon and insulin secretion through a precise cell-cell crosstalk. Paracrine interactions between pancreatic islet cells have been proposed as a mechanism to regulate hormone secretion and glucose homeostasis, alpha and B cells are closely positioned on the sides of their blood supply where acetylcholine acts as the paracrine communicator of signals inside the islets. Recently, it has been demonstrated that blocking acetylcholine esterase increases insulin secretion. Moreover, it has also been suggested that glucagon is not exclusively a counter-regulatory hormone that elevates blood glucose levels, in contrast it can cause hypoglycemia conditioned by the presence of intact B cells and a functional GLP-1R (glucagon-like peptide 1 receptor). These data argue for glucagon agonism in modern management of T2DM. Alpha-cells also, have been shown to be able to trans-differentiate into β-cells only in the presence of insulin-positive cells with α-cell origin in the lineage tracing analyses, confirming the role of α-cells as a source of β-cell regeneration. The article reviews the updated knowledge about the functions of the alpha-cells and its role in the paracrine control of islet cell secretions and the future therapeutic potentials.
VL  - 4
IS  - 4
ER  -

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