Catecholamine neurotransmitters dopamine (DA) and norepinephrine (NE) are essential for a myriad of functions throughout the central nervous system, including metabolic regulation. These molecules are also present in the pancreas, and their study may shed light on the effects of peripheral neurotransmission on glycemic control. Though sympathetic innervation to islets provides NE that signals at local α-cell and β-cell adrenergic receptors to modify hormone secretion, α-cells and β-cells also synthesize catecholamines locally. We propose a model where α-cells and β-cells take up catecholamine precursors in response to postprandial availability, preferentially synthesizing DA. The newly synthesized DA signals in an autocrine/paracrine manner to regulate insulin and glucagon secretion and maintain glycemic control. This enables islets to couple local catecholamine signaling to changes in nutritional state. We also contend that the DA receptors expressed by α-cells and β-cells are targeted by antipsychotic drugs (APDs)—some of the most widely prescribed medications today. Blockade of local DA signaling contributes significantly to APD-induced dysglycemia, a major contributor to treatment discontinuation and development of diabetes. Thus, elucidating the peripheral actions of catecholamines will provide new insights into the regulation of metabolic pathways and may lead to novel, more effective strategies to tune metabolism and treat diabetes.
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January 2023
Perspectives in Diabetes|
December 14 2022
Roles of Pancreatic Islet Catecholamine Neurotransmitters in Glycemic Control and in Antipsychotic Drug–Induced Dysglycemia
Zachary Freyberg
;
1Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA
2Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA
Corresponding authors: Zachary Freyberg, freyberg@pitt.edu, and George K. Gittes, gittesgk@upmc.edu
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George K. Gittes
3Division of Pediatric Surgery, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA
Corresponding authors: Zachary Freyberg, freyberg@pitt.edu, and George K. Gittes, gittesgk@upmc.edu
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Corresponding authors: Zachary Freyberg, freyberg@pitt.edu, and George K. Gittes, gittesgk@upmc.edu
Diabetes 2023;72(1):3–15
Article history
Received:
June 09 2022
Accepted:
September 24 2022
Citation
Zachary Freyberg, George K. Gittes; Roles of Pancreatic Islet Catecholamine Neurotransmitters in Glycemic Control and in Antipsychotic Drug–Induced Dysglycemia. Diabetes 1 January 2023; 72 (1): 3–15. https://doi.org/10.2337/db22-0522
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