Tanis: A Link Between Type 2 Diabetes and Inflammation?

Author:

Walder Ken1,Kantham Lakshmi1,McMillan Janine S.1,Trevaskis James1,Kerr Lyndal1,de Silva Andrea1,Sunderland Terry1,Godde Nathan1,Gao Yuan1,Bishara Natalie1,Windmill Kelly1,Tenne-Brown Janette1,Augert Guy2,Zimmet Paul Z.3,Collier Greg R.14

Affiliation:

1. Metabolic Research Unit, School of Health Sciences, Deakin University, Waurn Ponds, Victoria, Australia

2. Lipha SA Research and Development, Lyon, France

3. International Diabetes Institute, Caulfield, Australia

4. Autogen, 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.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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