Neuropeptide Y expression marks partially differentiated β cells in mice and humans

Rodnoi, Pope; Rajkumar, Mohan Singh; Moin, Abu Saleh Md; Georgia, Senta; Butler, Alexandra E.; Dhawan, Sangeeta

doi:10.1172/jci.insight.94005

Cited by 44 publications

(63 citation statements)

References 56 publications

(65 reference statements)

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“…Of these genes, we found that Npy mRNA was significantly elevated in Adrb2 cKO islets while Slc2a2 was decreased ( Figure 3F ). Npy encodes for Neuropeptide Y (NPY), a hormone that is normally downregulated in islets during postnatal development ( Myrsén-Axcrona et al, 1997 ), while its persistent expression in adult islets is associated with decreased β-cell responsiveness ( Gu et al, 2010 ; Rodnoi et al, 2017 ). Slc2a2 encodes for the β-cell-specific glucose transporter, Glut2, which is essential for GSIS in mature β-cells ( Thorens, 2003 ).…”

Section: Resultsmentioning

confidence: 99%

Adrb2 controls glucose homeostasis by developmental regulation of pancreatic islet vasculature

Ceasrine

Lin

Lumelsky

et al. 2018

eLife

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A better understanding of processes controlling the development and function of pancreatic islets is critical for diabetes prevention and treatment. Here, we reveal a previously unappreciated function for pancreatic β2-adrenergic receptors (Adrb2) in controlling glucose homeostasis by restricting islet vascular growth during development. Pancreas-specific deletion of Adrb2 results in glucose intolerance and impaired insulin secretion in mice, and unexpectedly, specifically in females. The metabolic phenotypes were recapitulated by Adrb2 deletion from neonatal, but not adult, β-cells. Mechanistically, Adrb2 loss increases production of Vascular Endothelial Growth Factor-A (VEGF-A) in female neonatal β-cells and results in hyper-vascularized islets during development, which in turn, disrupts insulin production and exocytosis. Neonatal correction of islet hyper-vascularization, via VEGF-A receptor blockade, fully rescues functional deficits in glucose homeostasis in adult mutant mice. These findings uncover a regulatory pathway that functions in a sex-specific manner to control glucose metabolism by restraining excessive vascular growth during islet development.

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Section: Resultsmentioning

confidence: 99%

Adrb2 controls glucose homeostasis by developmental regulation of pancreatic islet vasculature

Ceasrine

Lin

Lumelsky

et al. 2018

eLife

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“…Given the effects of NPY on the central stimulation of feeding behavior in rats, it is logical that NPY induces delayed and transient increases in circulating insulin. Furthermore, NPY can rapidly and transiently induce the phosphorylation of ERK1/2 to promote β-cell proliferation ( 126 , 127 ).…”

Section: Npy Indirectly Regulates the Immune Responsementioning

confidence: 99%

Neuropeptide Y Is an Immunomodulatory Factor: Direct and Indirect

Chen

Liu

et al. 2020

Front. Immunol.

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Neuropeptide Y (NPY), which is widely distributed in the nervous system, is involved in regulating a variety of biological processes, including food intake, energy metabolism, and emotional expression. However, emerging evidence points to NPY also as a critical transmitter between the nervous system and immune system, as well as a mediator produced and released by immune cells. In vivo and in vitro studies based on gene-editing techniques and specific NPY receptor agonists and antagonists have demonstrated that NPY is responsible for multifarious direct modulations on immune cells by acting on NPY receptors. Moreover, via the central or peripheral nervous system, NPY is closely connected to body temperature regulation, obesity development, glucose metabolism, and emotional expression, which are all immunomodulatory factors for the immune system. In this review, we focus on the direct role of NPY in immune cells and particularly discuss its indirect impact on the immune response.

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“…NPY has a critical impact upon the regulating secretory function of pancreatic α and β cells [116] as well as β cell differentiation both in mice and humans [117]. Under different circumstances, NPY can exert opposite functions upon the secretion of glucagon and insulin.…”

Section: The Characteristics Of Human Npy Receptorsmentioning

confidence: 99%

“…NPY-induced transient ERK1/2 phosphorylation can also promote the proliferation and replication of islet beta cells via the activation of extracellular signal-regulated kinase [116]. During the development of pancreas, NPY expression is restricted from the progenitor populations and marks functionally immature β cells in fetal and neonatal mice and humans [120]. NPY-positive cells were detectable in the central and periphery regions of islet cells in diabetic rats, although in normal rats, NPY-positive cells were only found in the peripheral regions of islet cells.…”

Section: The Characteristics Of Human Npy Receptorsmentioning

confidence: 99%

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A Promising Therapeutic Target for Metabolic Diseases: Neuropeptide Y Receptors in Humans

et al. 2017

Cell Physiol Biochem

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Human neuropeptide Y (hNPY) is one of the most widely expressed neurotransmitters in the human central and peripheral nervous systems. It consists of 36 highly conserved amino acid residues, and was first isolated from the porcine hypothalamus in 1982. While it is the most recently discovered member of the pancreatic polypeptide family (which includes neuropeptide Y, gut-derived hormone peptide YY, and pancreatic polypeptide), NPY is the most abundant peptide found in the mammalian brain. In order to exert particular functions, NPY needs to bind to the NPY receptor to activate specific signaling pathways. NPY receptors belong to the class A or rhodopsin-like G-protein coupled receptor (GPCR) family and signal via cell-surface receptors. By binding to GPCRs, NPY plays a crucial role in various biological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. Abnormal regulation of NPY is involved in the development of a wide range of diseases, including obesity, hypertension, atherosclerosis, epilepsy, metabolic disorders, and many cancers. Thus far, five receptors have been cloned from mammals (Y1, Y2, Y4, Y5, and y6), but only four of these (hY1, hY2, hY4, and hY5) are functional in humans. In this review, we summarize the structural characteristics of human NPY receptors and their role in metabolic diseases.

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Neuropeptide Y expression marks partially differentiated β cells in mice and humans

Cited by 44 publications

References 56 publications

Adrb2 controls glucose homeostasis by developmental regulation of pancreatic islet vasculature

Adrb2 controls glucose homeostasis by developmental regulation of pancreatic islet vasculature

Neuropeptide Y Is an Immunomodulatory Factor: Direct and Indirect

A Promising Therapeutic Target for Metabolic Diseases: Neuropeptide Y Receptors in Humans

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