Diabetic Phenotype in the Small Intestine of Zucker Diabetic Fatty Rats

Background/Aims: In contrast to streptozotocin (STZ)-induced rodent models of diabetes, there are no thorough characterizations of the intestinal phenotype and the underlying changes in the global gene-expression of genetic models of diabetes, such as the Zucker diabetic fatty (ZDF) rat. The aim of...

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Veröffentlicht in:Digestion 2016-01, Vol.94 (4), p.199-214
Hauptverfasser: Hvid, Henning, Jensen, Stina Rikke, Witgen, Brent M., Fledelius, Christian, Damgaard, Jesper, Pyke, Charles, Rasmussen, Thomas Bovbjerg
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container_end_page 214
container_issue 4
container_start_page 199
container_title Digestion
container_volume 94
creator Hvid, Henning
Jensen, Stina Rikke
Witgen, Brent M.
Fledelius, Christian
Damgaard, Jesper
Pyke, Charles
Rasmussen, Thomas Bovbjerg
description Background/Aims: In contrast to streptozotocin (STZ)-induced rodent models of diabetes, there are no thorough characterizations of the intestinal phenotype and the underlying changes in the global gene-expression of genetic models of diabetes, such as the Zucker diabetic fatty (ZDF) rat. The aim of the present study was to characterize the intestine in the ZDF rat. Methods: The intestine of ZDF rats and lean controls was examined macroscopically and histologically, and ribonucleic acid sequencing (RNAseq) was performed in samples of jejunal mucosa. Results: We observed an increased mass and length of the small and large intestines in ZDF rats. RNAseq showed an increased expression of Pdk2 and Pdk4, which are involved in the regulation of glucose and fatty acid metabolism, and increased expression of genes involved in gluconeogenesis and peroxisomal beta-oxidation in jejunal mucosa. Conclusion: Intestinal enlargement in ZDF rats is likely driven by increased food intake, since (i) it also occurs in obese and normoglycemic Zucker fatty rats, and (ii) insulin treatment of STZ-induced diabetic rats reduced the food intake and mass of the small intestine. Results from RNAseq indicate that small intestinal epithelial cells in ZDF rats have developed insulin resistance, and support that a normal physiological effect of insulin in the enterocytes is the regulation of glucose metabolism.
doi_str_mv 10.1159/000453107
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The aim of the present study was to characterize the intestine in the ZDF rat. Methods: The intestine of ZDF rats and lean controls was examined macroscopically and histologically, and ribonucleic acid sequencing (RNAseq) was performed in samples of jejunal mucosa. Results: We observed an increased mass and length of the small and large intestines in ZDF rats. RNAseq showed an increased expression of Pdk2 and Pdk4, which are involved in the regulation of glucose and fatty acid metabolism, and increased expression of genes involved in gluconeogenesis and peroxisomal beta-oxidation in jejunal mucosa. Conclusion: Intestinal enlargement in ZDF rats is likely driven by increased food intake, since (i) it also occurs in obese and normoglycemic Zucker fatty rats, and (ii) insulin treatment of STZ-induced diabetic rats reduced the food intake and mass of the small intestine. Results from RNAseq indicate that small intestinal epithelial cells in ZDF rats have developed insulin resistance, and support that a normal physiological effect of insulin in the enterocytes is the regulation of glucose metabolism.</description><identifier>ISSN: 0012-2823</identifier><identifier>EISSN: 1421-9867</identifier><identifier>DOI: 10.1159/000453107</identifier><identifier>PMID: 27931035</identifier><language>eng</language><publisher>Basel, Switzerland</publisher><subject>Animals ; Diabetes Mellitus, Experimental - genetics ; Diabetes Mellitus, Experimental - metabolism ; Gluconeogenesis ; Glucose - metabolism ; Insulin Resistance ; Intestinal Mucosa - enzymology ; Intestinal Mucosa - metabolism ; Intestinal Mucosa - pathology ; Intestine, Large - pathology ; Intestine, Small - enzymology ; Intestine, Small - metabolism ; Intestine, Small - pathology ; Male ; Obesity - metabolism ; Original Paper ; Phenotype ; Protein-Serine-Threonine Kinases - metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Zucker ; Sequence Analysis, RNA ; Sucrase - metabolism ; Transcriptome ; Up-Regulation</subject><ispartof>Digestion, 2016-01, Vol.94 (4), p.199-214</ispartof><rights>2016 S. Karger AG, Basel</rights><rights>2016 S. Karger AG, Basel.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-6fa681d99a6092dd9e5d1960544e17e59c44d0cd1bbe55bb7e39265a9a290f373</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,2423,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27931035$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hvid, Henning</creatorcontrib><creatorcontrib>Jensen, Stina Rikke</creatorcontrib><creatorcontrib>Witgen, Brent M.</creatorcontrib><creatorcontrib>Fledelius, Christian</creatorcontrib><creatorcontrib>Damgaard, Jesper</creatorcontrib><creatorcontrib>Pyke, Charles</creatorcontrib><creatorcontrib>Rasmussen, Thomas Bovbjerg</creatorcontrib><title>Diabetic Phenotype in the Small Intestine of Zucker Diabetic Fatty Rats</title><title>Digestion</title><addtitle>Digestion</addtitle><description>Background/Aims: In contrast to streptozotocin (STZ)-induced rodent models of diabetes, there are no thorough characterizations of the intestinal phenotype and the underlying changes in the global gene-expression of genetic models of diabetes, such as the Zucker diabetic fatty (ZDF) rat. 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subjects Animals
Diabetes Mellitus, Experimental - genetics
Diabetes Mellitus, Experimental - metabolism
Gluconeogenesis
Glucose - metabolism
Insulin Resistance
Intestinal Mucosa - enzymology
Intestinal Mucosa - metabolism
Intestinal Mucosa - pathology
Intestine, Large - pathology
Intestine, Small - enzymology
Intestine, Small - metabolism
Intestine, Small - pathology
Male
Obesity - metabolism
Original Paper
Phenotype
Protein-Serine-Threonine Kinases - metabolism
Rats
Rats, Sprague-Dawley
Rats, Zucker
Sequence Analysis, RNA
Sucrase - metabolism
Transcriptome
Up-Regulation
title Diabetic Phenotype in the Small Intestine of Zucker Diabetic Fatty Rats
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