Nampt/Pbef/Visfatin Regulates Insulin Secretion in Beta Cells As A Systemic Nad Biosynthetic Enzyme

Javier R. Revollo,Antje Koerner,Kathryn F. Mills,Akiko Satoh,Tao Wang,Antje Garten,Biplab Dasgupta,Yo Sasaki,Cynthia Wolberger,R. Reid Townsend,Jeffrey Milbrandt,Wieland Kiess,Shin-Ichiro Imai

Cell Metabolism（2007）SCI 1区

Cited 839|Views45

Abstract

Intracellular nicotinamide phosphoribosyltransferase (iNampt) is an essential enzyme in the NAD biosynthetic pathway. An extracellular form of this protein (eNampt) has been reported to act as a cytokine named PBEF or an insulin-mimetic hormone named visfatin, but its physiological relevance remains controversial. Here we show that eNampt does not exert insulin-mimetic effects in vitro or in vivo but rather exhibits robust NAD biosynthetic activity. Haplo-deficiency and chemical inhibition of Nampt cause defects in NAD biosynthesis and glucose-stimulated insulin secretion in pancreatic islets in vivo and in vitro. These defects are corrected by administration of nicotinamide mononucleotide (NMN), a product of the Nampt reaction. A high concentration of NMN is present in mouse plasma, and plasma eNampt and NMN levels are reduced in Nampt heterozygous females. Our results demonstrate that Nampt-mediated systemic NAD biosynthesis is critical for beta cell function, suggesting a vital framework for the regulation of glucose homeostasis.

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Key words

HUMDISEASE,SIGNALING

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