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10.1371/journal.pone.0177934 http://scihub22266oqcxt.onion/10.1371/journal.pone.0177934 C5436842!5436842 !28542433     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28542433 &cmd=llinks): Failed to open stream: HTTP request failed! 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Beneficial effect of combined treatment with octreotide and pasireotide in PCK rats, an orthologous model of human autosomal recessive polycystic kidney disease |pdf=|usr=}}{{28542433 }} gab.com Text Beneficial effect of combined treatment with octreotide and pasireotide in PCK rats, an orthologous model of human autosomal recessive polycystic kidney disease JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=28542433 #FOAvip Increased intracellular cyclic AMP (cAMP) in renal tubular epithelia accelerates the progression of polycystic kidney disease (PKD). Thus, decreasing cAMP levels by an adenylyl cyclase inhibitory G protein activator is considered to be an effective approach in ameliorating PKD. In fact, pasireotide (PAS) was effective in reducing disease progression in animal models of PKD. However, hyperglycemia caused by the administration of PAS is an adverse effect in its clinical use. Whereas, co-administration of octreotide (OCT) with PAS did not increase serum glucose in normal rats. In the current study, we examined the efficacy of combined treatment with OCT and PAS in PCK rats, an autosomal recessive PKD model. Four-week-old PCK males were treated with the long-acting release type of OCT, PAS, or a combination of both (OCT/PAS) for 12 weeks. After termination, serum and renal tissue were used for analyses. Kidney weight, kidney weight per body weight, renal cyst area, renal Ki67 expression, and serum urea nitrogen were significantly decreased either in the PAS or OCT/PAS group, compared with vehicle. Renal tissue cAMP content was significantly decreased by PAS or OCT/PAS treatment, but not OCT, compared with vehicle. As a marker of cellular mTOR signaling activity, renal phospho-S6 kinase expression was significantly decreased by OCT/PAS treatment compared with vehicle, OCT, or PAS. Serum glucose was significantly increased by PAS administration, whereas no difference was shown between vehicle and OCT/PAS, possibly because serum glucagon was decreased either by the treatment of OCT alone or co-application of OCT/PAS. In conclusion, since serum glucose levels are increased by the use of PAS, its combination with OCT may reduce the risk of hyperglycemia associated with PAS monotherapy against PKD progression. Twit Text FOAVip Beneficial effect of combined treatment with octreotide and pasireotide in PCK rats, an orthologous model of human autosomal recessive polycystic kidney disease ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=28542433 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28542433 #FOAvip English Wikipedia <ref>{{Cite pmid|28542433 }}</ref> Beneficial effect of combined treatment with octreotide and pasireotide in PCK rats, an orthologous model of human autosomal recessive polycystic kidney disease #MMPMID28542433 Kugita M ; Nishii K ; Yamaguchi T ; Suzuki A ; Yuzawa Y ; Horie S ; Higashihara E ; Nagao S PLoS One 2017[]; 12 (5 ): e0177934 PMID28542433 show ga Increased intracellular cyclic AMP (cAMP) in renal tubular epithelia accelerates the progression of polycystic kidney disease (PKD). Thus, decreasing cAMP levels by an adenylyl cyclase inhibitory G protein activator is considered to be an effective approach in ameliorating PKD. In fact, pasireotide (PAS) was effective in reducing disease progression in animal models of PKD. However, hyperglycemia caused by the administration of PAS is an adverse effect in its clinical use. Whereas, co-administration of octreotide (OCT) with PAS did not increase serum glucose in normal rats. In the current study, we examined the efficacy of combined treatment with OCT and PAS in PCK rats, an autosomal recessive PKD model. Four-week-old PCK males were treated with the long-acting release type of OCT, PAS, or a combination of both (OCT/PAS) for 12 weeks. After termination, serum and renal tissue were used for analyses. Kidney weight, kidney weight per body weight, renal cyst area, renal Ki67 expression, and serum urea nitrogen were significantly decreased either in the PAS or OCT/PAS group, compared with vehicle. Renal tissue cAMP content was significantly decreased by PAS or OCT/PAS treatment, but not OCT, compared with vehicle. As a marker of cellular mTOR signaling activity, renal phospho-S6 kinase expression was significantly decreased by OCT/PAS treatment compared with vehicle, OCT, or PAS. Serum glucose was significantly increased by PAS administration, whereas no difference was shown between vehicle and OCT/PAS, possibly because serum glucagon was decreased either by the treatment of OCT alone or co-application of OCT/PAS. In conclusion, since serum glucose levels are increased by the use of PAS, its combination with OCT may reduce the risk of hyperglycemia associated with PAS monotherapy against PKD progression. |Animals [MESH] |Blood Glucose/metabolism [MESH] |Body Weight/drug effects [MESH] |Cyclic AMP/metabolism [MESH] |Disease Models, Animal [MESH] |Drug Interactions [MESH] |Extracellular Signal-Regulated MAP Kinases/metabolism [MESH] |Glucagon/blood [MESH] |Heart/drug effects/physiology [MESH] |Humans [MESH] |Hydrocortisone/blood [MESH] |Hyperglycemia/chemically induced [MESH] |Insulin-Like Growth Factor I/metabolism [MESH] |Insulin/blood [MESH] |Ki-67 Antigen/metabolism [MESH] |Kidney/drug effects/metabolism/pathology/physiopathology [MESH] |Liver/drug effects/metabolism/pathology [MESH] |Male [MESH] |Octreotide/adverse effects/*pharmacology/therapeutic use [MESH] |Phosphoproteins/metabolism [MESH] |Polycystic Kidney, Autosomal Recessive/*drug therapy/metabolism/pathology/physiopathology [MESH] |Rats [MESH] |Receptor, IGF Type 1/blood [MESH] |Ribosomal Protein S6 Kinases/metabolism [MESH]Beneficial effect of combined treatment with octreotide and pasireotid(epmc).pdf DeepDyve Pubget Overpricing