PMID- 25979075
OWN - NLM
STAT- MEDLINE
DCOM- 20151117
LR  - 20181202
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 64
IP  - 9
DP  - 2015 Sep
TI  - The Metabolic Syndrome and Microvascular Complications in a Murine Model of Type 
      2 Diabetes.
PG  - 3294-304
LID - 10.2337/db15-0133 [doi]
AB  - 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, specifically 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.
CI  - (c) 2015 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.
FAU - Hur, Junguk
AU  - Hur J
AD  - Department of Neurology, University of Michigan, Ann Arbor, MI Department of 
      Basic Sciences, University of North Dakota, School of Medicine and Health 
      Sciences, Grand Forks, ND.
FAU - Dauch, Jacqueline R
AU  - Dauch JR
AD  - Department of Neurology, University of Michigan, Ann Arbor, MI.
FAU - Hinder, Lucy M
AU  - Hinder LM
AD  - Department of Neurology, University of Michigan, Ann Arbor, MI.
FAU - Hayes, John M
AU  - Hayes JM
AD  - Department of Neurology, University of Michigan, Ann Arbor, MI.
FAU - Backus, Carey
AU  - Backus C
AD  - Department of Neurology, University of Michigan, Ann Arbor, MI.
FAU - Pennathur, Subramaniam
AU  - Pennathur S
AD  - Division of Nephrology, Department of Internal Medicine, University of Michigan, 
      Ann Arbor, MI.
FAU - Kretzler, Matthias
AU  - Kretzler M
AD  - Division of Nephrology, Department of Internal Medicine, University of Michigan, 
      Ann Arbor, MI.
FAU - Brosius, Frank C 3rd
AU  - Brosius FC 3rd
AD  - Division of Nephrology, Department of Internal Medicine, University of Michigan, 
      Ann Arbor, MI.
FAU - Feldman, Eva L
AU  - Feldman EL
AD  - Department of Neurology, University of Michigan, Ann Arbor, MI 
      efeldman@med.umich.edu.
LA  - eng
GR  - 1DP3-DK-094292/DK/NIDDK NIH HHS/United States
GR  - DP3 DK094292/DK/NIDDK NIH HHS/United States
GR  - P30 DK092926/DK/NIDDK NIH HHS/United States
GR  - P30 DK020572/DK/NIDDK NIH HHS/United States
GR  - P30 DK081943/DK/NIDDK NIH HHS/United States
GR  - 930-DK-020572/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150515
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Triglycerides)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - Animals
MH  - Cholesterol/metabolism
MH  - Diabetes Mellitus, Type 2/complications/*metabolism
MH  - Diabetic Neuropathies/etiology/*physiopathology
MH  - Disease Models, Animal
MH  - Hypoglycemic Agents/*pharmacology
MH  - Lipoproteins, LDL/drug effects/metabolism
MH  - Metabolic Syndrome/complications/*metabolism
MH  - Mice
MH  - Nerve Fibers, Myelinated/drug effects
MH  - Nerve Fibers, Unmyelinated/drug effects
MH  - Neural Conduction/*drug effects/physiology
MH  - Oxidative Stress/drug effects
MH  - Pioglitazone
MH  - Sciatic Nerve/drug effects/physiopathology
MH  - Sural Nerve/drug effects/physiopathology
MH  - Thiazolidinediones/*pharmacology
MH  - Triglycerides/metabolism
MH  - Weight Gain/drug effects
PMC - PMC4542440
EDAT- 2015/05/17 06:00
MHDA- 2015/11/18 06:00
PMCR- 2016/09/01
CRDT- 2015/05/17 06:00
PHST- 2015/01/27 00:00 [received]
PHST- 2015/05/11 00:00 [accepted]
PHST- 2015/05/17 06:00 [entrez]
PHST- 2015/05/17 06:00 [pubmed]
PHST- 2015/11/18 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - db15-0133 [pii]
AID - 0133 [pii]
AID - 10.2337/db15-0133 [doi]
PST - ppublish
SO  - Diabetes. 2015 Sep;64(9):3294-304. doi: 10.2337/db15-0133. Epub 2015 May 15.