The role of pancreatic polypeptide in the regulation of energy homeostasis

Khandekar, Neeta; Berning, Britt A.; Sainsbury, Amanda; Lin, Shu

doi:10.1016/j.mce.2015.06.028

Cited by 32 publications

(28 citation statements)

References 141 publications

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“…(β) Beta; (α) alpha; (δ) delta; (γ) PP/gamma cells. (Khandekar et al 2015). Our data suggest interesting parallels in expression between PP/gamma cells and serotonergic neurons, a group of neurons that influence various cognitive and physiological processes including anxiety, mood, sleep, and satiety.…”

Section: Differential Expression Analyses Reveal Islet Cell-type-specmentioning

confidence: 68%

“…PP/gamma, along with epsilon cells, are among the least studied islet cell types due to their scarcity in islets. Recent studies show that PP/gamma cells are crucial regulators of energy homeostasis (Yulyaningsih et al 2014;Khandekar et al 2015). In response to food intake, these cells secrete the anorexigenic hormone PPY to (Dorrell et al 2011b;Bramswig et al 2013;Nica et al 2013;Blodgett et al 2015) confirmed to be expressed in each islet cell type after ANOVA and Tukey's honest significant difference (THSD) post-hoc analysis (Methods).…”

Section: Differential Expression Analyses Reveal Islet Cell-type-specmentioning

confidence: 99%

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Single-cell transcriptomes identify human islet cell signatures and reveal cell-type–specific expression changes in type 2 diabetes

et al. 2016

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Blood glucose levels are tightly controlled by the coordinated action of at least four cell types constituting pancreatic islets. Changes in the proportion and/or function of these cells are associated with genetic and molecular pathophysiology of monogenic, type 1, and type 2 (T2D) diabetes. Cellular heterogeneity impedes precise understanding of the molecular components of each islet cell type that govern islet (dys)function, particularly the less abundant delta and gamma/pancreatic polypeptide (PP) cells. Here, we report single-cell transcriptomes for 638 cells from nondiabetic (ND) and T2D human islet samples. Analyses of ND single-cell transcriptomes identified distinct alpha, beta, delta, and PP/gamma cell-type signatures. Genes linked to rare and common forms of islet dysfunction and diabetes were expressed in the delta and PP/gamma cell types. Moreover, this study revealed that delta cells specifically express receptors that receive and coordinate systemic cues from the leptin, ghrelin, and dopamine signaling pathways implicating them as integrators of central and peripheral metabolic signals into the pancreatic islet. Finally, single-cell transcriptome profiling revealed genes differentially regulated between T2D and ND alpha, beta, and delta cells that were undetectable in paired whole islet analyses. This study thus identifies fundamental cell-type-specific features of pancreatic islet (dys)function and provides a critical resource for comprehensive understanding of islet biology and diabetes pathogenesis.[Supplemental material is available for this article.]Pancreatic islets of Langerhans are clusters of at least four different hormone-secreting endocrine cell types that elicit coordinatedbut distinct-responses to maintain glucose homeostasis. As such, they are central to diabetes pathophysiology. On average, human islets consist mostly of beta (54%), alpha (35%), and delta (11%) cells; up to a few percent gamma/pancreatic polypeptide (PP) cells; and very few epsilon cells (Brissova et al. 2005;Cabrera et al. 2006;Blodgett et al. 2015). Human islet composition is neither uniform nor static but varies between individuals and across regions of the pancreas (Brissova et al. 2005;Cabrera et al. 2006;Blodgett et al. 2015). Cellular heterogeneity complicates molecular studies of whole human islets and may mask important role(s) for less common cells in the population (Dorrell et al. 2011b;Bramswig et al. 2013;Nica et al. 2013;Blodgett et al. 2015;Liu and Trapnell 2016). Moreover, it complicates attempts to identify epigenetic and transcriptional signatures distinguishing diabetic from nondiabetic (ND) islets, leading to inconsistent reports of genes and pathways affected (Gunton et al. 2005;Marselli et al. 2010;Taneera et al. 2012;Dayeh et al. 2014). Conventional sorting and enrichment techniques are unable to specifically purify each human islet cell type (Dorrell et al. 2008;Nica et al. 2013;Bramswig et al. 2013;Hrvatin et al. 2014;Blodgett et al. 2015), thus a precise understanding of the transcriptiona...

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Section: Differential Expression Analyses Reveal Islet Cell-type-specmentioning

confidence: 68%

Section: Differential Expression Analyses Reveal Islet Cell-type-specmentioning

confidence: 99%

Single-cell transcriptomes identify human islet cell signatures and reveal cell-type–specific expression changes in type 2 diabetes

et al. 2016

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“…Pancreatic polypeptide exerts a variety of regulatory functions, including central regulation of energy homeostasis and peripheral effects on secretion and gastrointestinal motility …”

Section: Introductionmentioning

confidence: 99%

“…Strong evidence exists that PP regulates energy homeostasis . In fact, it decreases food intake and increases energy expenditure via action on Y4 receptors in the hypothalamic arcuate nucleus .…”

Section: Introductionmentioning

confidence: 99%

Pancreatic polypeptide stimulates mouse gastric motor activity through peripheral neural mechanisms

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Caldara

et al. 2016

Neurogastroenterology Motil

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“…In addition to these gastrointestinal peptides, recent evidence has demonstrated that the intestinal microbiota is also linked to obesity and metabolic disorders. In this regard, Khandekar et al review the potentials of the anorexigenic factor, pancreatic polypeptide, as a target for the treatment of obesity, as well as the mechanisms involved in its effects (Khandekar et al, 2015). During the last years, several reports have demonstrated that glucagon-like peptide-1 based multiagonists are promising tools to treat obesity and type 2 diabetes, and the roles of these newly designed molecules is summarized by Finan et al (Finan et al, 2015).…”

mentioning

confidence: 99%