Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme.

By Javier R Revollo, A. Körner, K. Mills, A. Satoh, Tao Wang, A. Garten, B. Dasgupta, Y. Sasaki, C. Wolberger, R. Townsend and 3 more. Cell Metabolism, 2007

947 citations recorded by the source corpus.

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. Haplodeficiency 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.

Subfields: Geriatrics and Gerontology, Oncology, Physiology

View Paper: https://www.semanticscholar.org/paper/873947848f0bae0773adffb8a7e0f798a44bf641

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Geriatrics and Gerontology

1. Johan Auwerx
2. Jun Yoshino
3. S. Imai
4. C. Cantó
5. Keir J. Menzies
6. R. Houtkooper
7. K. Mills
8. Y. Sasaki

In Oncology

1. Johan Auwerx
2. Jun Yoshino
3. C. Cantó
4. S. Imai
5. R. Apte
6. R. Houtkooper
7. Joseph A. Baur

In Physiology

1. Johan Auwerx
2. S. Imai
3. Jun Yoshino
4. C. Cantó
5. Keir J. Menzies
6. R. Houtkooper
7. K. Walsh
8. Myung‐Sook Choi

Citations in the corpus

• Adipokines in inflammation and metabolic disease (2011, background): “Subsequently, it was reported to be mainly expressed and secreted by adipose tissues (in particular, visceral adipose tissue) through a non-classical secretory pathwa”
• Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease (2014, background): “Visfatin, which was previously identified as a modulator of β-cell differentiation that is expressed in a variety of tissues and cell types, including lymphocytes, bone marrow, muscle and liver [133], has been reported to be secreted by adipose tissue, especially visceral adipose tissue, and exhibit”
• NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus (2015, background): “This is partially corroborated by a report indicating that NMNmight be present in the bloodstream at concentrations around 50 mM (Revollo et al., 2007).”
• NAD+ intermediates: The biology and therapeutic potential of NMN and NR (2017, neutral): “It has also been reported that many different cell types, including adipocytes (Revollo et al., 2007; Yoon et al., 2015), hepatocytes (Schuster et al.”
• Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice (2016, positive): “Fed and fasted blood samples were collected monthly at the same time each month as described previously (Revollo et al., 2007) and used for glucose, insulin, blood cell counts, and lipid analysis (Yoshino et al., 2011).”
• Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. (2008, background): “Importantly, Nampt+/− heterozygous mice show impaired glucose tolerance and reduced glucose-stimulated insulin secretion (Revollo et al., 2007).”
• The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. (2010, background): “A third NAD salvage pathway, which was long known as the only NAD biosynthesis pathway in certain bacteria, is comprised of the phosphorylation of NR to NMN by NR kinase (NRK), after which one of the NMNAT enzymes catalyzes the formation of NAD .”
• Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice (2011, methodology): “Islet Isolation and In Vitro Insulin Secretion Analysis Islets were isolated from HFD-fed mice as described previously (Revollo et al., 2007).”
• The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity (2012, neutral): “(D) C57Bl/6J mice were fed with chow containing vehicle (water) or either NR, NMN or NA at 400 mg/ kg/day (n=8 mice per group).”