Cargando…
Therapeutic Impact of Leptin on Diabetes, Diabetic Complications, and Longevity in Insulin-Deficient Diabetic Mice
OBJECTIVE: The aim of the current study was to evaluate the long-term effects of leptin on glucose metabolism, diabetes complications, and life span in an insulin-dependent diabetes model, the Akita mouse. RESEARCH DESIGN AND METHODS: We cross-mated Akita mice with leptin-expressing transgenic (LepT...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161331/ https://www.ncbi.nlm.nih.gov/pubmed/21810600 http://dx.doi.org/10.2337/db10-1795 |
_version_ | 1782210678989258752 |
---|---|
author | Naito, Masaki Fujikura, Junji Ebihara, Ken Miyanaga, Fumiko Yokoi, Hideki Kusakabe, Toru Yamamoto, Yuji Son, Cheol Mukoyama, Masashi Hosoda, Kiminori Nakao, Kazuwa |
author_facet | Naito, Masaki Fujikura, Junji Ebihara, Ken Miyanaga, Fumiko Yokoi, Hideki Kusakabe, Toru Yamamoto, Yuji Son, Cheol Mukoyama, Masashi Hosoda, Kiminori Nakao, Kazuwa |
author_sort | Naito, Masaki |
collection | PubMed |
description | OBJECTIVE: The aim of the current study was to evaluate the long-term effects of leptin on glucose metabolism, diabetes complications, and life span in an insulin-dependent diabetes model, the Akita mouse. RESEARCH DESIGN AND METHODS: We cross-mated Akita mice with leptin-expressing transgenic (LepTg) mice to produce Akita mice with physiological hyperleptinemia (LepTg:Akita). Metabolic parameters were monitored for 10 months. Pair-fed studies and glucose and insulin tolerance tests were performed. The pancreata and kidneys were analyzed histologically. The plasma levels and pancreatic contents of insulin and glucagon, the plasma levels of lipids and a marker of oxidative stress, and urinary albumin excretion were measured. Survival rates were calculated. RESULTS: Akita mice began to exhibit severe hyperglycemia and hyperphagia as early as weaning. LepTg:Akita mice exhibited normoglycemia after an extended fast even at 10 months of age. The 6-h fasting blood glucose levels in LepTg:Akita mice remained about half the level of Akita mice throughout the study. Food intake in LepTg:Akita mice was suppressed to a level comparable to that in WT mice, but pair feeding did not affect blood glucose levels in Akita mice. LepTg:Akita mice maintained insulin hypersensitivity and displayed better glucose tolerance than did Akita mice throughout the follow-up. LepTg:Akita mice had normal levels of plasma glucagon, a marker of oxidative stress, and urinary albumin excretion rates. All of the LepTg:Akita mice survived for >12 months, the median mortality time of Akita mice. CONCLUSIONS: These results indicate that leptin is therapeutically useful in the long-term treatment of insulin-deficient diabetes. |
format | Online Article Text |
id | pubmed-3161331 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-31613312012-09-01 Therapeutic Impact of Leptin on Diabetes, Diabetic Complications, and Longevity in Insulin-Deficient Diabetic Mice Naito, Masaki Fujikura, Junji Ebihara, Ken Miyanaga, Fumiko Yokoi, Hideki Kusakabe, Toru Yamamoto, Yuji Son, Cheol Mukoyama, Masashi Hosoda, Kiminori Nakao, Kazuwa Diabetes Metabolism OBJECTIVE: The aim of the current study was to evaluate the long-term effects of leptin on glucose metabolism, diabetes complications, and life span in an insulin-dependent diabetes model, the Akita mouse. RESEARCH DESIGN AND METHODS: We cross-mated Akita mice with leptin-expressing transgenic (LepTg) mice to produce Akita mice with physiological hyperleptinemia (LepTg:Akita). Metabolic parameters were monitored for 10 months. Pair-fed studies and glucose and insulin tolerance tests were performed. The pancreata and kidneys were analyzed histologically. The plasma levels and pancreatic contents of insulin and glucagon, the plasma levels of lipids and a marker of oxidative stress, and urinary albumin excretion were measured. Survival rates were calculated. RESULTS: Akita mice began to exhibit severe hyperglycemia and hyperphagia as early as weaning. LepTg:Akita mice exhibited normoglycemia after an extended fast even at 10 months of age. The 6-h fasting blood glucose levels in LepTg:Akita mice remained about half the level of Akita mice throughout the study. Food intake in LepTg:Akita mice was suppressed to a level comparable to that in WT mice, but pair feeding did not affect blood glucose levels in Akita mice. LepTg:Akita mice maintained insulin hypersensitivity and displayed better glucose tolerance than did Akita mice throughout the follow-up. LepTg:Akita mice had normal levels of plasma glucagon, a marker of oxidative stress, and urinary albumin excretion rates. All of the LepTg:Akita mice survived for >12 months, the median mortality time of Akita mice. CONCLUSIONS: These results indicate that leptin is therapeutically useful in the long-term treatment of insulin-deficient diabetes. American Diabetes Association 2011-09 2011-08-20 /pmc/articles/PMC3161331/ /pubmed/21810600 http://dx.doi.org/10.2337/db10-1795 Text en © 2011 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Metabolism Naito, Masaki Fujikura, Junji Ebihara, Ken Miyanaga, Fumiko Yokoi, Hideki Kusakabe, Toru Yamamoto, Yuji Son, Cheol Mukoyama, Masashi Hosoda, Kiminori Nakao, Kazuwa Therapeutic Impact of Leptin on Diabetes, Diabetic Complications, and Longevity in Insulin-Deficient Diabetic Mice |
title | Therapeutic Impact of Leptin on Diabetes, Diabetic Complications, and Longevity in Insulin-Deficient Diabetic Mice |
title_full | Therapeutic Impact of Leptin on Diabetes, Diabetic Complications, and Longevity in Insulin-Deficient Diabetic Mice |
title_fullStr | Therapeutic Impact of Leptin on Diabetes, Diabetic Complications, and Longevity in Insulin-Deficient Diabetic Mice |
title_full_unstemmed | Therapeutic Impact of Leptin on Diabetes, Diabetic Complications, and Longevity in Insulin-Deficient Diabetic Mice |
title_short | Therapeutic Impact of Leptin on Diabetes, Diabetic Complications, and Longevity in Insulin-Deficient Diabetic Mice |
title_sort | therapeutic impact of leptin on diabetes, diabetic complications, and longevity in insulin-deficient diabetic mice |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161331/ https://www.ncbi.nlm.nih.gov/pubmed/21810600 http://dx.doi.org/10.2337/db10-1795 |
work_keys_str_mv | AT naitomasaki therapeuticimpactofleptinondiabetesdiabeticcomplicationsandlongevityininsulindeficientdiabeticmice AT fujikurajunji therapeuticimpactofleptinondiabetesdiabeticcomplicationsandlongevityininsulindeficientdiabeticmice AT ebiharaken therapeuticimpactofleptinondiabetesdiabeticcomplicationsandlongevityininsulindeficientdiabeticmice AT miyanagafumiko therapeuticimpactofleptinondiabetesdiabeticcomplicationsandlongevityininsulindeficientdiabeticmice AT yokoihideki therapeuticimpactofleptinondiabetesdiabeticcomplicationsandlongevityininsulindeficientdiabeticmice AT kusakabetoru therapeuticimpactofleptinondiabetesdiabeticcomplicationsandlongevityininsulindeficientdiabeticmice AT yamamotoyuji therapeuticimpactofleptinondiabetesdiabeticcomplicationsandlongevityininsulindeficientdiabeticmice AT soncheol therapeuticimpactofleptinondiabetesdiabeticcomplicationsandlongevityininsulindeficientdiabeticmice AT mukoyamamasashi therapeuticimpactofleptinondiabetesdiabeticcomplicationsandlongevityininsulindeficientdiabeticmice AT hosodakiminori therapeuticimpactofleptinondiabetesdiabeticcomplicationsandlongevityininsulindeficientdiabeticmice AT nakaokazuwa therapeuticimpactofleptinondiabetesdiabeticcomplicationsandlongevityininsulindeficientdiabeticmice |