Glicentin-related pancreatic polypeptide inhibits glucose-stimulated insulin secretion from the isolated pancreas of adult male rats

Whiting, Lynda; Stewart, Kevin; Hay, Debbie L.; Harris, Paul W. R.; Choong, Y.S.; Phillips, Anthony R. J.; Brimble, Margaret A.; Cooper, Garth J. S.

doi:10.14814/phy2.12638

Cited by 11 publications

(16 citation statements)

References 58 publications

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“…Of interest, MCP-1 (CCL-2) secretion from isolated human islets has been associated with enhanced glucose responsiveness and restoration of the peri-islet ECM capsule postisolation, indicating this profile may represent a beneficial effect [73,74]. Further, increased secretion of these cytokines within ECM hydrogel cultures may be attributed to the increased presence of islet-resident pro-angiogenic CD31 + endothelial cells and fibroblastlike cells [75][76][77][78].…”

Section: Discussionmentioning

confidence: 99%

3-D physiomimetic extracellular matrix hydrogels provide a supportive microenvironment for rodent and human islet culture

et al. 2019

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Organ-on-a-chip platforms serve as cost-efficient testbeds for screening pharmaceutical agents, mimicking natural physiology, and studying disease. In the field of diabetes, the development of an islet-on-a-chip platform would have broad implications in understanding disease pathology and discovering potential therapies. Islet microphysiological systems are limited, however, by their poor cell survival and function in culture. A key factor that has been implicated in this decline is the disruption of islet-matrix interactions following isolation. Herein, we sought to recapitulate the in vivo peri-islet niche using decellularized extracellular matrix (ECM) hydrogels. Sourcing from porcine bladder, lung, and pancreas tissues, 3-D ECM hydrogels were generated, characterized, and validated using both rodent and human pancreatic islets. Optimized decellularization protocols resulted in hydrogels with distinctive viscoelastic properties that correlated to their matrix composition. The in situ 3-D encapsulation of human or rat islets within ECM hydrogels resulted in improved functional stability over standard culture conditions. Islet composition and morphology were also altered, with enhanced retention of islet-resident endothelial cells and the formation of cord-like structures or sprouts emerging from the islet spheroid. These supportive 3-D physiomimetic ECM hydrogels can be leveraged within microfluidic platforms for the long-term culture of islets.

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Section: Discussionmentioning

confidence: 99%

3-D physiomimetic extracellular matrix hydrogels provide a supportive microenvironment for rodent and human islet culture

et al. 2019

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“…Interestingly, 7B2 and proSAAS are more widely distributed than Pc2 and Pc1/3 in islet and other endocrine cell types, suggesting they have non‐PC regulatory functions. One potential non‐PC function of both proSAAS and 7B2 is their reported inhibitory action on IAPP aggregation …”

Section: Islet Endocrine Cell Prohormone Processingmentioning

confidence: 99%

Islet prohormone processing in health and disease

Chen

Taylor

Verchere

2018

Diabetes Obesity Metabolism

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Biosynthesis of peptide hormones by pancreatic islet endocrine cells is a tightly orchestrated process that is critical for metabolic homeostasis. Like neuroendocrine peptides, insulin and other islet hormones are first synthesized as larger precursor molecules that are processed to their mature secreted products through a series of proteolytic cleavages, mediated by the prohormone convertases Pc1/3 and Pc2, and carboxypeptidase E. Additional posttranslational modifications including C-terminal amidation of the β-cell peptide islet amyloid polypeptide (IAPP) by peptidyl-glycine α-amidating monooxygenase (Pam) may also occur. Genome-wide association studies (GWAS) have showed genetic linkage of these processing enzymes to obesity, β-cell dysfunction, and type 2 diabetes (T2D), pointing to their important roles in metabolism and blood glucose regulation. In both type 1 diabetes (T1D) and T2D, and in the face of metabolic or inflammatory stresses, islet prohormone processing may become impaired; indeed elevated proinsulin:insulin (PI:I) ratios are a hallmark of the β-cell dysfunction in T2D. Recent studies suggest that genetic or acquired defects in proIAPP processing may lead to the production and secretion of incompletely processed forms of proIAPP that could contribute to T2D pathogenesis, and additionally that impaired processing of both PI and proIAPP may be characteristic of β-cell dysfunction in T1D. In islet α-cells, the prohormone proglucagon is normally processed to bioactive glucagon by Pc2 but may express Pc1/3 under certain conditions leading to production of GLP-1(7-36 ). A better understanding of how β-cell processing of PI and proIAPP, as well as α-cell processing of proglucagon, are impacted by genetic susceptibility and in the face of diabetogenic stresses, may lead to new therapeutic approaches for improving islet function in diabetes.

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“…The posttranslational regulation of proglucagon gene generates a number of well-known hormones, such as glucagon and glucagon like peptide 1 (GLP-1), and also other bioactive peptides like glucagon like peptide 2 (GLP-2), glicentin, glicentin-related pancreatic polypeptide (GRPP), and oxyntomodulin (OXM). Most of these proglucagon-derived peptides show very specific effects on glucose and energy balance, although some of them exhibit unclear functional roles [6,7,8,9,10]. The tissues-specific expression of various products from the proglucagon gene depend on posttranslational modifications by specific prohormone convertases (PC) [11].…”

Section: Introductionmentioning

confidence: 99%

Glucagon Control on Food Intake and Energy Balance

Al‐Massadi

Fernø

Diéguez

et al. 2019

IJMS

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Glucagon exerts pleiotropic actions on energy balance and has emerged as an attractive target for the treatment of diabetes and obesity in the last few years. Glucagon reduces body weight and adiposity by suppression of appetite and by modulation of lipid metabolism. Moreover, this hormone promotes weight loss by activation of energy expenditure and thermogenesis. In this review, we cover these metabolic actions elicited by glucagon beyond its canonical regulation of glucose metabolism. In addition, we discuss recent developments of therapeutic approaches in the treatment of obesity and diabetes by dual- and tri-agonist molecules based on combinations of glucagon with other peptides. New strategies using these unimolecular polyagonists targeting the glucagon receptor (GCGR), have become successful approaches to evaluate the multifaceted nature of glucagon signaling in energy balance and metabolic syndrome.

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Glicentin-related pancreatic polypeptide inhibits glucose-stimulated insulin secretion from the isolated pancreas of adult male rats

Cited by 11 publications

References 58 publications

3-D physiomimetic extracellular matrix hydrogels provide a supportive microenvironment for rodent and human islet culture

3-D physiomimetic extracellular matrix hydrogels provide a supportive microenvironment for rodent and human islet culture

Islet prohormone processing in health and disease

Glucagon Control on Food Intake and Energy Balance

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