Juvenile murine models of prediabetes and type 2 diabetes develop neuropathy
Peripheral neuropathy (neuropathy) is a common complication of obesity and type 2 diabetes in children and adolescents. To model this complication in mice, 5-week-old male C57BL/6J mice were fed a high-fat diet to induce diet-induced obesity (DIO), a model of prediabetes, and a cohort of these anima...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2018-12-01
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| Series: | Disease Models & Mechanisms |
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| Online Access: | http://dmm.biologists.org/content/11/12/dmm037374 |
| _version_ | 1811233440819838976 |
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| author | Phillipe D. O'Brien Lucy M. Hinder Amy E. Rumora John M. Hayes Jacqueline R. Dauch Carey Backus Faye E. Mendelson Eva L. Feldman |
| author_facet | Phillipe D. O'Brien Lucy M. Hinder Amy E. Rumora John M. Hayes Jacqueline R. Dauch Carey Backus Faye E. Mendelson Eva L. Feldman |
| author_sort | Phillipe D. O'Brien |
| collection | DOAJ |
| description | Peripheral neuropathy (neuropathy) is a common complication of obesity and type 2 diabetes in children and adolescents. To model this complication in mice, 5-week-old male C57BL/6J mice were fed a high-fat diet to induce diet-induced obesity (DIO), a model of prediabetes, and a cohort of these animals was injected with low-dose streptozotocin (STZ) at 12 weeks of age to induce hyperglycemia and type 2 diabetes. Neuropathy assessments at 16, 24 and 36 weeks demonstrated that DIO and DIO-STZ mice displayed decreased motor and sensory nerve conduction velocities as early as 16 weeks, hypoalgesia by 24 weeks and cutaneous nerve fiber loss by 36 weeks, relative to control mice fed a standard diet. Interestingly, neuropathy severity was similar in DIO and DIO-STZ mice at all time points despite significantly higher fasting glucose levels in the DIO-STZ mice. These mouse models provide critical tools to better understand the underlying pathogenesis of prediabetic and diabetic neuropathy from youth to adulthood, and support the idea that hyperglycemia alone does not drive early neuropathy. This article has an associated First Person interview with the first author of the paper. |
| first_indexed | 2024-04-12T11:20:16Z |
| format | Article |
| id | doaj.art-9b149fbcbee14aa4948c000a484b4045 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-04-12T11:20:16Z |
| publishDate | 2018-12-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-9b149fbcbee14aa4948c000a484b40452022-12-22T03:35:24ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112018-12-01111210.1242/dmm.037374037374Juvenile murine models of prediabetes and type 2 diabetes develop neuropathyPhillipe D. O'Brien0Lucy M. Hinder1Amy E. Rumora2John M. Hayes3Jacqueline R. Dauch4Carey Backus5Faye E. Mendelson6Eva L. Feldman7 Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA Peripheral neuropathy (neuropathy) is a common complication of obesity and type 2 diabetes in children and adolescents. To model this complication in mice, 5-week-old male C57BL/6J mice were fed a high-fat diet to induce diet-induced obesity (DIO), a model of prediabetes, and a cohort of these animals was injected with low-dose streptozotocin (STZ) at 12 weeks of age to induce hyperglycemia and type 2 diabetes. Neuropathy assessments at 16, 24 and 36 weeks demonstrated that DIO and DIO-STZ mice displayed decreased motor and sensory nerve conduction velocities as early as 16 weeks, hypoalgesia by 24 weeks and cutaneous nerve fiber loss by 36 weeks, relative to control mice fed a standard diet. Interestingly, neuropathy severity was similar in DIO and DIO-STZ mice at all time points despite significantly higher fasting glucose levels in the DIO-STZ mice. These mouse models provide critical tools to better understand the underlying pathogenesis of prediabetic and diabetic neuropathy from youth to adulthood, and support the idea that hyperglycemia alone does not drive early neuropathy. This article has an associated First Person interview with the first author of the paper.http://dmm.biologists.org/content/11/12/dmm037374Mouse modelsObesityPeripheral neuropathyPrediabetesType 2 diabetes |
| spellingShingle | Phillipe D. O'Brien Lucy M. Hinder Amy E. Rumora John M. Hayes Jacqueline R. Dauch Carey Backus Faye E. Mendelson Eva L. Feldman Juvenile murine models of prediabetes and type 2 diabetes develop neuropathy Disease Models & Mechanisms Mouse models Obesity Peripheral neuropathy Prediabetes Type 2 diabetes |
| title | Juvenile murine models of prediabetes and type 2 diabetes develop neuropathy |
| title_full | Juvenile murine models of prediabetes and type 2 diabetes develop neuropathy |
| title_fullStr | Juvenile murine models of prediabetes and type 2 diabetes develop neuropathy |
| title_full_unstemmed | Juvenile murine models of prediabetes and type 2 diabetes develop neuropathy |
| title_short | Juvenile murine models of prediabetes and type 2 diabetes develop neuropathy |
| title_sort | juvenile murine models of prediabetes and type 2 diabetes develop neuropathy |
| topic | Mouse models Obesity Peripheral neuropathy Prediabetes Type 2 diabetes |
| url | http://dmm.biologists.org/content/11/12/dmm037374 |
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