Tony K.T. Lam

Tony K.T. Lam, PhD

As the John Kitson McIvor (1915-1942) Endowed Chair in Diabetes Research and the Canada Research Chair in Obesity, I am interested in glucose and energy homeostasis and their roles in diabetes and obesity. Our main focus has been to elucidate nutrient and hormone sensing mechanisms in the gut and the brain that regulate hepatic glucose production, hepatic VLDL-TG (very low density lipoprotein triglycerides) secretion and food intake to maintain glucose, lipid and energy homeostasis.

We have discovered that nutrient sensing in the duodenum triggers hormonal signaling and a gut-brain-liver axis to inhibit glucose production and lower plasma glucose levels. We have identified intestinal signaling defects that are acquired in diabetes and obesity and have characterized novel molecular signaling pathways that can be activated to bypass intestinal signaling defects and restore glucose homeostasis.

In addition, we have discovered that jejunual nutrient sensing is necessary for duodenal-jejunal bypass to rapidly lower glucose levels in uncontrolled diabetes. Lastly, we have unveiled novel insulin, glucagon and nutrient signaling pathways in the brain that regulate hepatic glucose production, VLDL-TG secretion and food intake.

In summary, our discoveries reveal molecular targets in the gut and the brain that may carry therapeutic potential to lower blood glucose and lipid levels and body weight in diabetes and obesity.
  • Selected Publications
    • Rasmussen BA et al. Jejunal leptin-PI3K signaling lowers glucose production. Cell Metabolism 19(1):155-161, 2014
    • Mighiu PI, Yue JT et al. Hypothalamic glucagon signaling inhibits hepatic glucose production. Nature Medicine 19(6):766-772, 2013
    • Filippi BM et al. Insulin activates Erk1/2 signaling in the dorsal vagal complex to inhibit glucose production. Cell Metabolism 16:500-510, 2012
    • Breen DM et al. Jejunal nutrient sensing is required for duodenal-jejunal bypass surgery to rapidly lower glucose concentrations in uncontrolled diabetes. Nature Medicine 18:950-955, 2012. (Live Interview at Nature Medicine Podcast: Time 16:06)
    • Yue JT and Lam TKT. Lipid sensing and insulin resistance in the brain. Cell Metabolism 15:646-655, 2012
    • Yue JT et al. Glycine normalizes hepatic triglyeride-rich VLDL secretion by triggering the CNS in high-fat fed rats. Circulation Research 110:1345-54, 2012
    • Lam TKT: Neuronal regulation of homeostasis by nutrient sensing. Nature Medicine 16:392-395, 2010
    • Cheung G et al. Intestinal cholecystokinin controls glucose production through a neuronal network. Cell Metabolism 10:99-109, 2009 (Cover story, TV Interview)
    • Wang P et al. Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production. Nature 452:1012-1016, 2008 (Named a 2008 Milestone in Canadian Health Research by Canadian Institutes of Health Research)
    • Caspi L et al. A balance of lipid-sensing mechanisms in the brain and liver. Cell Metabolism 6:99-104, 2007
    • Lam TKT et al. Regulation of blood glucose by hypothalamic pyruvate metabolism. Science 309(5736):943, 2005
J Clin Invest. 2017 Jan 03;127(1):33-42
Winer DA, Winer S, Dranse HJ, Lam TK
Ergonomics. 2015;58(10):1682-9
McGill S, Frost D, Lam T, Finlay T, Darby K, Cannon J
Nat Commun. 2016 Nov 22;7:13501
Yue JT, Abraham MA, Bauer PV, LaPierre MP, Wang P, Duca FA, Filippi BM, Chan O, Lam TK
Int J Radiat Oncol Biol Phys. 2016 Oct 1;96(2S):E270
McPartlin A, Hosni A, Lam T, Rosewall T, Warde PR, Chung P
Diabetologia. 2016 Jul;59(7):1367-71
Abraham MA, Lam TK
J Biol Chem. 2016 Apr 15;291(16):8816-24
Zadeh-Tahmasebi M, Duca FA, Rasmussen BA, Bauer PV, Côté CD, Filippi BM, Lam TK
Nat Med. 2016 Feb;22(2):217
Duca FA, Côté CD, Rasmussen BA, Zadeh-Tahmasebi M, Rutter GA, Filippi BM, Lam TK



John Kitson McIvor (1915-1942) Endowed Chair in Diabetes Research
Canada Research Chair in Obesity
Full Professor, Departments of Physiology and Medicine, University of Toronto
Associate Director of Research, Banting and Best Diabetes Centre, University of Toronto