Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice

Samuel A J Trammell; Benjamin J Weidemann; Ankita Chadda; Matthew S Yorek; Amey Holmes; Lawrence J Coppey; Alexander Obrosov; Randy H Kardon; Mark A Yorek; Charles Brenner

doi:10.1038/srep26933

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Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice

Journal article

Open access

Peer reviewed

Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice

Samuel A J Trammell, Benjamin J Weidemann, Ankita Chadda, Matthew S Yorek, Amey Holmes, Lawrence J Coppey, Alexander Obrosov, Randy H Kardon, Mark A Yorek and Charles Brenner

Scientific reports, Vol.6(1), 26933

05/27/2016

DOI: 10.1038/srep26933

PMCID: PMC4882590

PMID: 27230286

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https://doi.org/10.1038/srep26933View

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Abstract

Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD(+) metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP(+) and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies.

Niacinamide - analogs & derivatives

Prediabetic State - metabolism

Diabetes Mellitus, Experimental - drug therapy

Liver - pathology

Obesity - drug therapy

Streptozocin

Male

Insulin - blood

Prediabetic State - drug therapy

Cornea - drug effects

Liver - drug effects

Diet, High-Fat

Obesity - etiology

Cornea - pathology

Diabetes Mellitus, Experimental - chemically induced

Prediabetic State - pathology

Diabetes Mellitus, Experimental - metabolism

Prediabetic State - etiology

Diabetic Neuropathies - prevention & control

Liver - metabolism

Mice, Inbred C57BL

Insulin Resistance

Hypoglycemic Agents - pharmacology

Obesity - metabolism

Obesity - pathology

Animals

Diabetic Neuropathies - pathology

Diabetes Mellitus, Experimental - pathology

Cornea - innervation

Mice

Niacinamide - pharmacology

Blood Glucose - metabolism

Diabetic Neuropathies - metabolism

Diabetic Neuropathies - chemically induced

Details

Title: Subtitle: Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice
Creators: Samuel A J Trammell - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Benjamin J Weidemann - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Ankita Chadda - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Matthew S Yorek - Iowa City Veterans Administration, Iowa City, IA 52246, USA
Amey Holmes - Iowa City Veterans Administration, Iowa City, IA 52246, USA
Lawrence J Coppey - Iowa City Veterans Administration, Iowa City, IA 52246, USA
Alexander Obrosov - Iowa City Veterans Administration, Iowa City, IA 52246, USA
Randy H Kardon - Department of Opthalmology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Mark A Yorek - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Charles Brenner - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Scientific reports, Vol.6(1), 26933
DOI: 10.1038/srep26933
PMID: 27230286
PMCID: PMC4882590
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: I01 BX001680 / BLRD VA R01 DK081147 / NIDDK NIH HHS I01 RX000889 / RRD VA R21 AA022371 / NIAAA NIH HHS
Language: English
Date published: 05/27/2016
Academic Unit: Iowa Neuroscience Institute; Biochemistry and Molecular Biology; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9983788431502771

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