Orphaned No More? Glucose-Sensing Hypothalamic Neurons Control Insulin Secretion

Mobbs, Charles V.

doi:10.2337/dbi16-0027

Cited by 3 publications

(4 citation statements)

References 19 publications

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“…The central nervous system plays a key role in regulating many important metabolic functions, including the maintenance of euglycemia (131)(132)(133)(134). Specifically, a subpopulation of neurons in the arcuate nucleus of the hypothalamus (ARC) that store and release several orexigenic agents, including AgRP, NPY, and GABA (AgRP neurons), has been the focus of intense investigation.…”

Section: Agrp Neuronsmentioning

confidence: 99%

β-Arrestins as Important Regulators of Glucose and Energy Homeostasis

Pydi

Barella

Zhu

et al. 2022

Annu. Rev. Physiol.

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β-Arrestin-1 and -2 (also known as arrestin-2 and -3, respectively) are ubiquitously expressed cytoplasmic proteins that dampen signaling through G protein–coupled receptors. However, β-arrestins can also act as signaling molecules in their own right. To investigate the potential metabolic roles of the two β-arrestins in modulating glucose and energy homeostasis, recent studies analyzed mutant mice that lacked or overexpressed β-arrestin-1 and/or -2 in distinct, metabolically important cell types. Metabolic analysis of these mutant mice clearly demonstrated that both β-arrestins play key roles in regulating the function of most of these cell types, resulting in striking changes in whole-body glucose and/or energy homeostasis. These studies also revealed that β-arrestin-1 and -2, though structurally closely related, clearly differ in their metabolic roles under physiological and pathophysiological conditions. These new findings should guide the development of novel drugs for the treatment of various metabolic disorders, including type 2 diabetes and obesity. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Section: Agrp Neuronsmentioning

confidence: 99%

β-Arrestins as Important Regulators of Glucose and Energy Homeostasis

Pydi

Barella

Zhu

et al. 2022

Annu. Rev. Physiol.

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“…Obesity is associated with numerous comorbidities, including type 2 diabetes (T2D) and fatty liver disease (1)(2)(3)(4). It is well known that distinct areas of the brain play important roles in maintaining euglycemia (5)(6)(7)(8). In particular, neuronal subpopulations of the arcuate nucleus of the hypothalamus (ARC) have been studied in great detail because of their known effects on key metabolic functions (6,(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

“…The function of AgRP neurons and other hypothalamic neurons is regulated by various nutrients, metabolites, and hormones, including insulin and leptin (7,8,10,14,17). In turn, efferent signals from AgRP neurons and other ARC neurons control hepatic glucose production (HGP), the activity of brown adipose tissue (BAT), and the secretion of hormones from pancreatic islets (5,16,18,19).…”

Section: Introductionmentioning

confidence: 99%

Beneficial metabolic role of β-arrestin-1 expressed by AgRP neurons

Pydi

Cui

et al. 2020

Sci. Adv.

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β-Arrestin-1 and β-arrestin-2 have emerged as important signaling molecules that modulate glucose fluxes in several peripheral tissues. The potential roles of neuronally expressed β-arrestins in regulating glucose homeostasis remain unknown. We here report that mice lacking β-arrestin-1 (barr1) selectively in AgRP neurons displayed impaired glucose tolerance and insulin sensitivity when consuming an obesogenic diet, while mice overexpressing barr1 selectively in AgRP neurons were protected against obesity-associated metabolic impairments. Additional physiological, biochemical, and electrophysiological data indicated that the presence of barr1 is essential for insulin-mediated hyperpolarization of AgRP neurons. As a result, barr1 expressed by AgRP neurons regulates efferent neuronal pathways that suppress hepatic glucose production and promote lipolysis in adipose tissue. Mice lacking β-arrestin-2 (barr2) selectively in AgRP neurons showed no substantial metabolic phenotypes. Our data suggest that agents able to enhance the activity of barr1 in AgRP neurons may prove beneficial as antidiabetic drugs.

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“…This has been confirmed by a study documented that the β cells function and insulin action were under control of hypothalamic neurons. This has been confirmed by induction of c-Fos expression (the marker of neurons activity) in hypothalamic neurons after peripheral glucose injection (Mobbs 2016). Thus, this may provide an evidence that PYY 3-36 improved IR and enhanced insulin action on glucose elimination through hypothalamic Y 2 receptors (van den Hoek et al 2007).…”

Section: Discussionmentioning

confidence: 87%

The effect of peptide tyrosine tyrosine (PYY_3–36), a selective Y2 receptor agonist on streptozotocin-induced diabetes in albino rats

Abdel-Hamid

Abdalla

Zenhom

et al. 2019

Endocrine Regulations

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Objective. The aim of the present study was to assess the effect of the PYY3–36, as a potential therapy for the type 2 diabetes mellitus (T2DM), induced by high fat diet (HFD) and an intraperitoneal (i.p.) administration of streptozotocin (STZ) in albino rats.Methods. Forty adult male albino Wistar rats were divided into: 1) control group (C, in which the rats were fed with a standard diet and received vehicle; 2) diabetic group (D, in which T2DM was induced by feeding the rats with HFD for four weeks followed by a single i.p. injection of 35 mg/kg STZ, this group was also allowed to have HFD till the end of the study; and 3) D+PYY3–36 group (in which the diabetic rats were treated with 50 µg/kg i.p. PYY3–36 twice a day for one week). Food intake, water intake, body weight (b.w.), visceral fat weight (VFW), liver glycogen content, serum levels of glucose, insulin, and interleukin-6 (IL-6), were measured. Homeostatic-model assessment of insulin resistance (HOMA-IR) was estimated. The gene expression of the hypothalamic neuropeptide Y (NPY) and visceral nuclear factor kappa B (NF-κB) were assessed by a reverse transcription polymerase chain reaction (RT-PCR).Results. The PYY3–36 administration to the diabetic group of rats significantly increased the serum insulin levels and liver glycogen content, decreased the body weight, VFW, food intake, water intake, serum levels of the glucose, IL-6, and HOMA-IR. It also decreased the expression of both the hypothalamic NPY and the visceral fat NF-κB.Conclusion. With respect to the fact of improved insulin release and enhanced insulin sensitivity (an effect that may be mediated via suppressing accumulation of visceral fat and inflammatory markers), in the rats treated with PYY3–36, the PYY3–36 might be considered for the future as a promising therapeutic tool in T2DM.

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Orphaned No More? Glucose-Sensing Hypothalamic Neurons Control Insulin Secretion

Cited by 3 publications

References 19 publications

β-Arrestins as Important Regulators of Glucose and Energy Homeostasis

β-Arrestins as Important Regulators of Glucose and Energy Homeostasis

Beneficial metabolic role of β-arrestin-1 expressed by AgRP neurons

The effect of peptide tyrosine tyrosine (PYY_3–36), a selective Y2 receptor agonist on streptozotocin-induced diabetes in albino rats

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Orphaned No More? Glucose-Sensing Hypothalamic Neurons Control Insulin Secretion

Cited by 3 publications

References 19 publications

β-Arrestins as Important Regulators of Glucose and Energy Homeostasis

β-Arrestins as Important Regulators of Glucose and Energy Homeostasis

Beneficial metabolic role of β-arrestin-1 expressed by AgRP neurons

The effect of peptide tyrosine tyrosine (PYY3–36), a selective Y2 receptor agonist on streptozotocin-induced diabetes in albino rats

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The effect of peptide tyrosine tyrosine (PYY_3–36), a selective Y2 receptor agonist on streptozotocin-induced diabetes in albino rats