Tanis: A Link Between Type 2 Diabetes and Inflammation?
- Ken Walder1,
- Lakshmi Kantham1,
- Janine S. McMillan1,
- James Trevaskis1,
- Lyndal Kerr1,
- Andrea de Silva1,
- Terry Sunderland1,
- Nathan Godde1,
- Yuan Gao1,
- Natalie Bishara1,
- Kelly Windmill1,
- Janette Tenne-Brown1,
- Guy Augert2,
- Paul Z. Zimmet3 and
- Greg R. Collier14
- 1Metabolic Research Unit, School of Health Sciences, Deakin University, Waurn Ponds, Victoria, Australia
- 2Lipha SA Research and Development, Lyon, France
- 3International Diabetes Institute, Caulfield, Australia
- 4Autogen, South Melbourne, Australia
Abstract
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.
Footnotes
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Address correspondence and reprint requests to Ken Walder, School of Health Sciences, Deakin University, Waurn Ponds, Victoria 3217, Australia. E-mail: walder{at}deakin.edu.au.
Received for publication 11 September 2001 and accepted in revised form 25 February 2002.
P.Z.Z. receives laboratory funds from Autogen, a biotechnology company involved in the discovery of genes and proteins in diabetes and obesity.
3AT, 3-amino-1,2,4-triazole; IGT, impaired glucose tolerant; NGT, normal glucose tolerant; RU, resonance units; SAA, serum amyloid A; SPR, surface plasmon resonance.
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