PYY-Dependent Restoration of Impaired Insulin and Glucagon Secretion in Type 2 Diabetes following Roux-En-Y Gastric Bypass Surgery

Ramracheya, Reshma; McCulloch, Laura; Clark, Anne; Wiggins, David; Johannessen, Helene; Olsen, Magnus Kringstad; Cai, Xing; Zhao, Chun‐Mei; Chen, Duan; Rorsman, Patrik

doi:10.1016/j.celrep.2016.03.091

Cited by 76 publications

(94 citation statements)

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“…Mouse and Wistar rat islets were isolated by collagenase type V (Sigma‐Aldrich Ltd, Gillingham, UK) digestion as described previously . For optimal yield, GK rat islets were isolated by liberase as before . A typical islet yield per mouse, Wistar rat and GK rat was 250, 400 and 200, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Sham or RYGB surgery was performed on anesthetized rats as previously described . Briefly, the intestine was transected 10 cm distal to the ligament of Treitz, creating a distal and a proximal end.…”

Section: Methodsmentioning

confidence: 99%

“…Similarly, overexpression of PYY in mouse pancreatic beta‐cells results in improved glucose tolerance . Marked elevations in plasma PYY levels have been reported following RYGB in both humans and rats . Moreover, PYY pre‐treatment of islets isolated from severely diabetic GK rats has been shown to restore impaired insulin and glucagon responses to glucose .…”

Section: Introductionmentioning

confidence: 99%

“…Peptide tyrosine tyrosine (PYY) is an appetite‐regulating hormone that has been shown to play a critical role in the restoration of impaired islet secretory function in diabetic rats and following Roux‐En‐Y gastric bypass (RYGB) . The physiological relevance of PYY in pancreatic islets has been demonstrated by dramatic disruption of islet structure and beta‐cell function in mice following selective ablation of PYY‐expressing islet cells and by restoration of beta‐cell function by exogenous application of PYY in streptozotocin‐treated mice .…”

Section: Introductionmentioning

confidence: 99%

“…Recent reports suggest that acute administration of PYY reduces insulin secretion in isolated mouse islets and human/rodent beta cell lines . On the other hand, insulinotropic effects of PYY have been reported in 2 transgenic mouse models as well as in mouse and human islets . PYY signals through a cluster of receptors belonging to the neuropeptide Y (NPY) family, of which there are 4 subtypes; NPY1R, NPY2R, NPY4R and NPY5R.…”

Section: Introductionmentioning

confidence: 99%

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Sitagliptin and Roux‐en‐Y gastric bypass modulate insulin secretion via regulation of intra‐islet PYY

Guida

McCulloch

Godazgar

et al. 2017

Diabetes Obesity Metabolism

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AimsThe gut hormone peptide tyrosine tyrosine (PYY) is critical for maintaining islet integrity and restoring islet function following Roux‐en‐Y gastric bypass (RYGB). The expression of PYY and its receptors (NPYRs) in islets has been documented but not fully characterized. Modulation of islet PYY by the proteolytic enzyme dipeptidyl peptidase IV (DPP‐IV) has not been investigated and the impact of DPP‐IV inhibition on islet PYY function remains unexplored. Here we have addressed these gaps and their effects on glucose‐stimulated insulin secretion (GSIS). We have also investigated changes in pancreatic PYY in diabetes and following RYGB.MethodsImmunohistochemistry and gene expression analysis were used to assess PYY, NPYRs and DPP‐IV expression in rodent and human islets. DPP‐IV activity inhibition was achieved by sitagliptin. Secretion studies were used to test PYY and the effects of sitagliptin on insulin release, and the involvement of GLP‐1. Radioimmunoassays were used to measure hormone content in islets.ResultsPYY and DPP‐IV localized in different cell types in islets while NPYR expression was confined to the beta‐cells. Chronic PYY application enhanced GSIS in rodent and diabetic human islets. DPP‐IV inhibition by sitagliptin potentiated GSIS; this was mediated by locally‐produced PYY, and not GLP‐1. Pancreatic PYY was markedly reduced in diabetes. RYGB strongly increased islet PYY content, but did not lead to full restoration of pancreatic GLP‐1 levels.ConclusionLocal regulation of pancreatic PYY, rather than GLP‐1, by DPP‐IV inhibition or RYGB can directly modulate the insulin secretory response to glucose, indicating a novel role of pancreatic PYY in diabetes and weight‐loss surgery.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Sitagliptin and Roux‐en‐Y gastric bypass modulate insulin secretion via regulation of intra‐islet PYY

Guida

McCulloch

Godazgar

et al. 2017

Diabetes Obesity Metabolism

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Endocrine Function after Bariatric Surgery

Kim

Sandoval

2017

Comprehensive Physiology

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Obesity increases the risks of metabolic disorders including type 2 diabetes mellitus (T2DM). Bariatric surgery is the most successful therapeutic option that causes sustained weight loss and improvements in obesity comorbidities. Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are two of the most frequently performed bariatric surgeries. Despite their different anatomical rearrangement, they have remarkably similar success in both weight loss and T2DM remission. Interestingly, they also both cause a wide range of endocrine changes. Many of these endocrine changes are reflected specifically within the intestine and are implicated as mechanisms for the metabolic success of surgery. However, while most of the work shows that these hormonal changes are associated with the metabolic changes after surgery, causation has been difficult to ascertain. Here, we review the endocrine changes after RYGB and VSG and explore their mechanistic role in the success of bariatric surgery. Further, we explore important changes in gastrointestinal function and the role of these changes in the increase in postprandial endocrine responses after bariatric surgery. © 2017 American Physiological Society. Compr Physiol 7:783-798, 2017.

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Distribution and Stimulus Secretion Coupling of Enteroendocrine Cells along the Intestinal Tract

Adriaenssens

Reimann

Gribble

2018

Comprehensive Physiology

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The enteroendocrine system of the gut acts both locally and peripherally, regulating gastrointestinal function as well as metabolism, energy expenditure, and central appetite control through the release of a variety of hormones. The chemosensing ability of enteroendocrine cells is integral to their role in eliciting physiological changes in response to fluctuations in the composition of the intestinal lumen. Regulation of enteroendocrine cell activity is complex, and requires that these cells can integrate signals deriving from dietary sources as well as the nervous and endocrine systems. Here, we provide an overview of enteroendocrine cell form and function, with a focus on new insights into their distribution throughout the intestine and the stimulus secretion coupling mechanisms underlying the activity of these important members of the gut-brain axis. © 2018 American Physiological Society. Compr Physiol 8:1603-1638, 2018.

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PYY-Dependent Restoration of Impaired Insulin and Glucagon Secretion in Type 2 Diabetes following Roux-En-Y Gastric Bypass Surgery

Cited by 76 publications

References 28 publications

Sitagliptin and Roux‐en‐Y gastric bypass modulate insulin secretion via regulation of intra‐islet PYY

Sitagliptin and Roux‐en‐Y gastric bypass modulate insulin secretion via regulation of intra‐islet PYY

Endocrine Function after Bariatric Surgery

Distribution and Stimulus Secretion Coupling of Enteroendocrine Cells along the Intestinal Tract

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