Shin-ichiro Imai, MD, PhD

Shin-ichiro Imai, MD, PhD

Professor of Developmental Biology

Research Interest

Metabolic Regulation and Obesity

Signal Transduction/Hormone Action

Islet Biology and Immunology

Prevention and Control

Category(ies) of Research


Descriptor of Research

We have recently demonstrated that both high-fat diet (HFD) and aging compromise NAD biosynthesis mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD biosynthetic pathway from nicotinamide, resulting in significant decreases in NAMPT protein and NAD levels in multiple metabolic tissues. These defects contribute to insulin resistance in the liver and impaired glucose-stimulated insulin secretion (GSIS) in pancreatic  cells. Strikingly, administration of nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD intermediate, can significantly ameliorate defects in insulin sensitivity and GSIS in type 2 diabetic model mice. For example, in the HFD-fed diabetic liver, NMN enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through the activation of the NAD-dependent protein deacetylase SIRT1. Furthermore, NAD and NAMPT levels show significant decreases in multiple organs during aging, and NMN improves glucose intolerance and lipid profiles in age-induced diabetic mice. These findings provide critical insights into a novel nutriceutical intervention against diet- and age-induced type 2 diabetes. These findings were published in the October issue of Cell Metabolism (Yoshino, Mills et al. 14: 528-536, 2011).

Developmental Biology