Role of Insulin Resistance in the Pathogenesis and Development of Type 2 Diabetes in WBN/Kob-Leprfa Rats
WBN/Kob-Leprfa (fa/fa) rats have been identified as a new animal model of type 2 diabetes (T2DM), as they are characterized by impaired pancreatic insulin secretion and severe insulin resistance. Our previous study demonstrated impaired insulin secretion and its involvement in hyperglycemia in fa/fa...
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The Japanese Society of Veterinary Science
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942958/ |
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pubmed-39429582014-04-22 Role of Insulin Resistance in the Pathogenesis and Development of Type 2 Diabetes in WBN/Kob-Leprfa Rats OKUNO, Akira KAJI, Noriyuki TAKAHASHI, Atsushi NAGAKUBO, Dai OHNO-ICHIKI, Kanako SHIRAI, Mitsuyuki ASAI, Fumitoshi Pharmacology WBN/Kob-Leprfa (fa/fa) rats have been identified as a new animal model of type 2 diabetes (T2DM), as they are characterized by impaired pancreatic insulin secretion and severe insulin resistance. Our previous study demonstrated impaired insulin secretion and its involvement in hyperglycemia in fa/fa rats. The present study was aimed at elucidating the role of insulin resistance in the development and progression of diabetes in these animals. Troglitazone (TGZ) was used as an insulin sensitizer. Insulin resistance and insulin secretory capacity were measured by a homeostasis model assessment of insulin resistance and the area under the blood concentration–time curve for plasma insulin levels after intravenous glucose tolerance testing, respectively. The fa/fa rats exhibited marked insulin resistance between 5 and 11 weeks of age, compared with age-matched Wistar rats. The insulin secretory capacity of fa/fa rats was higher than that of Wistar rats at 5 weeks of age, but decreased by 50% between 9 and 11 weeks of age. The fa/fa rats were fed a standard diet, with or without 0.2% w/w TGZ, for 4 weeks. Treatment with TGZ significantly improved insulin resistance, hyperglycemia and hypertriglyceridemia in both prophylactic and therapeutic study groups. These results suggest that insulin resistance is markedly involved in the development and progression of T2DM in fa/fa rats. The Japanese Society of Veterinary Science 2013-07-26 2013-12 /pmc/articles/PMC3942958/ /pubmed/23892462 http://dx.doi.org/10.1292/jvms.13-0230 Text en ©2013 The Japanese Society of Veterinary Science http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
OKUNO, Akira KAJI, Noriyuki TAKAHASHI, Atsushi NAGAKUBO, Dai OHNO-ICHIKI, Kanako SHIRAI, Mitsuyuki ASAI, Fumitoshi |
| spellingShingle |
OKUNO, Akira KAJI, Noriyuki TAKAHASHI, Atsushi NAGAKUBO, Dai OHNO-ICHIKI, Kanako SHIRAI, Mitsuyuki ASAI, Fumitoshi Role of Insulin Resistance in the Pathogenesis and Development of Type 2 Diabetes in WBN/Kob-Leprfa Rats |
| author_facet |
OKUNO, Akira KAJI, Noriyuki TAKAHASHI, Atsushi NAGAKUBO, Dai OHNO-ICHIKI, Kanako SHIRAI, Mitsuyuki ASAI, Fumitoshi |
| author_sort |
OKUNO, Akira |
| title |
Role of Insulin Resistance in the Pathogenesis and Development of Type 2
Diabetes in WBN/Kob-Leprfa
Rats |
| title_short |
Role of Insulin Resistance in the Pathogenesis and Development of Type 2
Diabetes in WBN/Kob-Leprfa
Rats |
| title_full |
Role of Insulin Resistance in the Pathogenesis and Development of Type 2
Diabetes in WBN/Kob-Leprfa
Rats |
| title_fullStr |
Role of Insulin Resistance in the Pathogenesis and Development of Type 2
Diabetes in WBN/Kob-Leprfa
Rats |
| title_full_unstemmed |
Role of Insulin Resistance in the Pathogenesis and Development of Type 2
Diabetes in WBN/Kob-Leprfa
Rats |
| title_sort |
role of insulin resistance in the pathogenesis and development of type 2
diabetes in wbn/kob-leprfa
rats |
| description |
WBN/Kob-Leprfa
(fa/fa) rats have been identified as a new animal model of type 2
diabetes (T2DM), as they are characterized by impaired pancreatic insulin secretion and
severe insulin resistance. Our previous study demonstrated impaired insulin secretion and
its involvement in hyperglycemia in fa/fa rats. The present study was
aimed at elucidating the role of insulin resistance in the development and progression of
diabetes in these animals. Troglitazone (TGZ) was used as an insulin sensitizer. Insulin
resistance and insulin secretory capacity were measured by a homeostasis model assessment
of insulin resistance and the area under the blood concentration–time curve for plasma
insulin levels after intravenous glucose tolerance testing, respectively. The
fa/fa rats exhibited marked insulin resistance between 5 and 11 weeks
of age, compared with age-matched Wistar rats. The insulin secretory capacity of
fa/fa rats was higher than that of Wistar rats at 5 weeks of age, but
decreased by 50% between 9 and 11 weeks of age. The fa/fa rats were fed a
standard diet, with or without 0.2% w/w TGZ, for 4 weeks. Treatment with TGZ significantly
improved insulin resistance, hyperglycemia and hypertriglyceridemia in both prophylactic
and therapeutic study groups. These results suggest that insulin resistance is markedly
involved in the development and progression of T2DM in fa/fa rats. |
| publisher |
The Japanese Society of Veterinary Science |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942958/ |
| _version_ |
1612064530675793920 |