Juvenile murine models of prediabetes and type 2 diabetes develop neuropathy.

Autor:	O'Brien PD; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Hinder LM; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Rumora AE; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Hayes JM; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Dauch JR; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Backus C; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Mendelson FE; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Feldman EL; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA efeldman@umich.edu.
Jazyk:	angličtina
Zdroj:	Disease models & mechanisms [Dis Model Mech] 2018 Dec 18; Vol. 11 (12). Date of Electronic Publication: 2018 Dec 18.
DOI:	10.1242/dmm.037374
Abstrakt:	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. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2018. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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