The metabolic syndrome and microvascular complications in a murine model of type 2 diabetes

Junguk Hur, Jacqueline R. Dauch, Lucy M. Hinder, John M. Hayes, Carey Backus, Subramaniam Pennathur, Matthias Kretzler, Frank C. Brosius, Eva L. Feldman

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

To define the components of the metabolic syndrome that contribute to diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM), we treated the BKS db/db mouse, an established murine model of T2DM and the metabolic syndrome, with the thiazolidinedione class drug pioglitazone. Pioglitazone treatment of BKS db/db mice produced a significant weight gain, restored glycemic control, and normalized measures of serum oxidative stress and triglycerides but had no effect on LDLs or total cholesterol. Moreover, although pioglitazone treatment normalized renal function, it had no effect on measures of large myelinated nerve fibers, specifi-cally sural or sciatic nerve conduction velocities, but significantly improved measures of small unmyelinated nerve fiber architecture and function. Analyses of gene expression arrays of large myelinated sciatic nerves from pioglitazone-treated animals revealed an unanticipated increase in genes related to adipogenesis, adipokine signaling, and lipoprotein signaling, which likely contributed to the blunted therapeutic response. Similar analyses of dorsal root ganglion neurons revealed a salutary effect of pioglitazone on pathways related to defense and cytokine production. These data suggest differential susceptibility of small and large nerve fibers to specific metabolic impairments associated with T2DM and provide the basis for discussion of new treatment paradigms for individuals with T2DM and DPN.

Original languageEnglish (US)
Pages (from-to)3294-3304
Number of pages11
JournalDiabetes
Volume64
Issue number9
DOIs
StatePublished - Sep 2015

Fingerprint

pioglitazone
Type 2 Diabetes Mellitus
Diabetic Neuropathies
Sciatic Nerve
Myelinated Nerve Fibers
Adipogenesis
Sural Nerve
Unmyelinated Nerve Fibers
Adipokines
Neural Conduction
Spinal Ganglia
Therapeutics
Nerve Fibers
Lipoproteins
Weight Gain
Triglycerides
Oxidative Stress
Cholesterol
Cytokines
Kidney

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Hur, J., Dauch, J. R., Hinder, L. M., Hayes, J. M., Backus, C., Pennathur, S., ... Feldman, E. L. (2015). The metabolic syndrome and microvascular complications in a murine model of type 2 diabetes. Diabetes, 64(9), 3294-3304. https://doi.org/10.2337/db15-0133

The metabolic syndrome and microvascular complications in a murine model of type 2 diabetes. / Hur, Junguk; Dauch, Jacqueline R.; Hinder, Lucy M.; Hayes, John M.; Backus, Carey; Pennathur, Subramaniam; Kretzler, Matthias; Brosius, Frank C.; Feldman, Eva L.

In: Diabetes, Vol. 64, No. 9, 09.2015, p. 3294-3304.

Research output: Contribution to journalArticle

Hur, J, Dauch, JR, Hinder, LM, Hayes, JM, Backus, C, Pennathur, S, Kretzler, M, Brosius, FC & Feldman, EL 2015, 'The metabolic syndrome and microvascular complications in a murine model of type 2 diabetes', Diabetes, vol. 64, no. 9, pp. 3294-3304. https://doi.org/10.2337/db15-0133
Hur J, Dauch JR, Hinder LM, Hayes JM, Backus C, Pennathur S et al. The metabolic syndrome and microvascular complications in a murine model of type 2 diabetes. Diabetes. 2015 Sep;64(9):3294-3304. https://doi.org/10.2337/db15-0133
Hur, Junguk ; Dauch, Jacqueline R. ; Hinder, Lucy M. ; Hayes, John M. ; Backus, Carey ; Pennathur, Subramaniam ; Kretzler, Matthias ; Brosius, Frank C. ; Feldman, Eva L. / The metabolic syndrome and microvascular complications in a murine model of type 2 diabetes. In: Diabetes. 2015 ; Vol. 64, No. 9. pp. 3294-3304.
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