Tanis: a link between type 2 diabetes and inflammation?
Here we describe a novel protein, which we have named Tanis, that is implicated in type 2 diabetes and inflammation. In Psammomys obesus, a unique polygenic animal model of type 2 diabetes and the metabolic syndrome, Tanis is expressed in the liver in inverse proportion to circulating glucose (P = 0.010) and insulin levels (P = 0.004) and in direct proportion with plasma triglyceride concentrations (P = 0.007). Hepatic Tanis gene expression was markedly increased (3.1-fold) after a 24-h fast in diabetic but not in nondiabetic P. obesus. In addition, glucose inhibited Tanis gene expression in cultured hepatocytes (P = 0.006) as well as in several other cell types (P = 0.001-0.011). Thus, Tanis seems to be regulated by glucose and is dysregulated in the diabetic state. Yeast-2 hybrid screening identified serum amyloid A (SAA), an acute-phase inflammatory response protein, as an interacting protein of Tanis, and this was confirmed by Biacore experiments. SAA and other acute-phase proteins have been the focus of recent attention as risk factors for cardiovascular disease, and we contend that Tanis and its interaction with SAA may provide a mechanistic link among type 2 diabetes, inflammation, and cardiovascular disease.
Walder
Ken
K
Metabolic Research Unit, School of Health Sciences, Deakin University, Waurn Ponds, Victoria, Australia. walder@deakin.edu.au
Kantham
Lakshmi
L
McMillan
Janine S
JS
Trevaskis
James
J
Kerr
Lyndal
L
De Silva
Andrea
A
Sunderland
Terry
T
Godde
Nathan
N
Gao
Yuan
Y
Bishara
Natalie
N
Windmill
Kelly
K
Tenne-Brown
Janette
J
Augert
Guy
G
Zimmet
Paul Z
PZ
Collier
Greg R
GR
D000595:Amino Acid Sequence; D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D001483:Base Sequence; D001786:Blood Glucose / Q000032:analysis; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005091:Exons; D015870:Gene Expression / Q000187:drug effects; D005849:Gerbillinae; D005947:Glucose / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000737:chemistry; D012307:Risk Factors; D016415:Sequence Alignment; D000685:Serum Amyloid A Protein / Q000378:metabolism
D001053:Apolipoproteins; D001786:Blood Glucose; D008565:Membrane Proteins; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; C457119:tanis protein, Psammomys obesus; D005947:Glucose