title: Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice.
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.
authors.affiliation: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Samuel A J
authors.initials: SA
authors.lastname: Trammell
authors.affiliation: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Weidemann
authors.affiliation: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Ankita
authors.initials: A
authors.lastname: Chadda
authors.affiliation: Iowa City Veterans Administration, Iowa City, IA 52246, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Yorek
authors.affiliation: Iowa City Veterans Administration, Iowa City, IA 52246, USA.
authors.forename: Amey
authors.initials: A
authors.lastname: Holmes
authors.affiliation: Iowa City Veterans Administration, Iowa City, IA 52246, USA.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Coppey
authors.affiliation: Iowa City Veterans Administration, Iowa City, IA 52246, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Obrosov
authors.affiliation: Iowa City Veterans Administration, Iowa City, IA 52246, USA.|Department of Opthalmology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Randy H
authors.initials: RH
authors.lastname: Kardon
authors.affiliation: Iowa City Veterans Administration, Iowa City, IA 52246, USA.|Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Yorek
authors.affiliation: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.|Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Brenner
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003315:Cornea / Q000187:drug effects / Q000294:innervation / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003929:Diabetic Neuropathies / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D059305:Diet, High-Fat; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011236:Prediabetic State / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011726:Pyridinium Compounds; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D011726:Pyridinium Compounds; C018613:nicotinamide-beta-riboside; D009536:Niacinamide; D013311:Streptozocin