Role of uroguanylin's signalling pathway in the development of ischaemic stroke

Ratko, Martina; Habek, Nikola; Radmilović, Marina Dobrivojević; Škokić, Siniša; Justić, Helena; Barić, Anja; Dugandžić, Aleksandra

doi:10.1111/ejn.15674

Cited by 2 publications

(1 citation statement)

References 60 publications

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“…Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) are enzymatically cleaved, and active peptides can activate hypothalamic and midbrain circuits that decrease appetite upon binding GUCY2C ( 19 – 21 ). Uroguanylin also increases Ca 2+ concentrations in astrocytes via GUCY2C-dependent signalling pathway modulating neuronal activity in cerebral and cerebellar cortex ( 22 , 23 ). Guanylin peptides are involved in the regulation of food preferences ( 24 , 25 ), adiposity, and energy expenditure ( 26 – 28 ) via central and peripheral mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery

et al. 2023

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IntroductionObesity contributes to ectopic fat deposition in non-adipose organs, including the pancreas. Pancreas steatosis associates with inflammation and β-cell dysfunction, contributing to the onset of insulin resistance and type 2 diabetes. An improvement of pancreatic steatosis and indices of insulin resistance is observed following bariatric surgery, but the underlying mechanisms remain unknown. We sought to analyze whether guanylin (GUCA2A) and uroguanylin (GUCA2B), two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of pancreas fat accumulation after bariatric surgery.MethodsPancreas steatosis, inflammation, islet number and area were measured in male Wistar rats with diet-induced obesity (n=125) subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by gastrectomized animals) interventions. The tissue distribution of guanylate cyclase C (GUCY2C) and the expression of the guanylin system were evaluated in rat pancreata by real-time PCR, Western-blot and immunohistochemistry. The effect of guanylin and uroguanylin on factors involved in insulin secretion and lipogenesis was determined in vitro in RIN-m5F β-cells exposed to lipotoxic conditions.ResultsSleeve gastrectomy reduced pancreas steatosis and inflammation and improved insulin sensitivity and synthesis. An upregulation of GUCA2A and GUCY2C, but not GUCA2B, was observed in pancreata from rats with diet-induced obesity one month after sleeve gastrectomy. Interestingly, both guanylin and uroguanylin diminished the lipotoxicity in palmitate-treated RIN-m5F β-cells, evidenced by lower steatosis and downregulated lipogenic factors Srebf1, Mogat2 and Dgat1. Both guanylin peptides reduced insulin synthesis (Ins1 and Ins2) and release from RIN-m5F β-cells, but only guanylin upregulated Wnt4, a factor that controls β-cell proliferation and function.DiscussionTogether, sleeve gastrectomy reduced pancreatic steatosis and improved β-cell function. Several mechanisms, including the modulation of inflammation and lipogenesis as well as the upregulation of GUCA2A in the pancreas, might explain this beneficial effect of bariatric surgery.

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Section: Introductionmentioning

confidence: 99%

Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery

et al. 2023

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Role of uroguanylin's signalling pathway in the development of ischaemic stroke

Ratko

Habek

Radmilović

et al. 2022

Eur J of Neuroscience

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Stroke is one of the leading causes of mortality and disability worldwide. By affecting bradykinin function, activation of guanylate cyclase (GC)-A has been shown to have a neuroprotective effect after ischaemic stroke, whereas the same has not been confirmed for GC-B; therefore, we aimed to determine the possible role of GC-C and its agonist, uroguanylin (UGN), in the development of stroke. In this study, middle cerebral artery occlusion (MCAO) was performed on wild-type (WT), GC-C KO and UGN KO mice. MR images were acquired before and 24 h after MCAO. On brain slices 48 h after MCAO, the Ca 2+ response to UGN stimulation was recorded. Our results showed that the absence of GC-C in GC-C KO mice resulted in the development of smaller ischaemic lesions compared with WT littermates, which is an opposite effect compared with the effects of GC-A agonists on brain lesions. WT and UGN KO animals showed a stronger Ca 2+ response upon UGN stimulation in astrocytes of the peri-ischaemic cerebral cortex compared with the same cortical region of the unaffected contralateral hemisphere. This stronger activation was not observed in GC-C KO animals, which may be the reason for smaller lesion development in GC-C KO mice. The reason why GC-C might affect Ca 2+ signalling in peri-ischaemic astrocytes is that GC-C is expressed in these cells after MCAO, whereas under normoxic conditions, it is expressed mainly in cortical neurons. Stronger activation of the Ca 2+ -dependent signalling pathway could lead to the stronger activation of the Na + /H + exchanger, tissue acidification and neuronal death.

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Role of uroguanylin's signalling pathway in the development of ischaemic stroke

Cited by 2 publications

References 60 publications

Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery

Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery

Role of uroguanylin's signalling pathway in the development of ischaemic stroke

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