Dr. Lam
 Contact Information:
Phone: 416-581-7880
Phone 2: 416-581-7697 (lab)
Email: tony.lam@uhnres.utoronto.ca
Address:

Toronto General Research Institute
MaRS Centre, Toronto Medical Discovery Tower
Room 10-705, 101 College Street
Toronto, ON Canada M5G 1L7



Primary Appointment:  Associate Professor (cross appointed in Medicine); John Kitson McIvor Endowed Chair in Diabetes Research; Canada Research Chair in Obesity

Degrees:  Ph.D. 2003

Affiliation:  Scientist, Toronto General Research Institute, University Health Network

Research Divisions: Endocrine and Diabetes Platform

Keywords: Nutrient sensing / Diabetes / Obesity

Research Interests:  Diabetes and obesity are characterized by a disruption in glucose and energy homeostasis. A disruption in glucose and energy homeostasis is caused, in part, by an elevation of hepatic glucose production and food intake, respectively. The long-term goal of my laboratory is to unveil novel molecules/pathways in the body that regulate both hepatic glucose production and food intake in vivo, and consequently revealing new therapeutic molecules that could be targeted to restore glucose and energy homeostasis in diabetes and obesity. 

CNS nutrient-sensing mechanisms. The central nervous system, or more specifically the hypothalamus, has received much attention recently in diabetes and obesity research. This is based on the fact that the hypothalamus could detect an acute rise in nutrients or fat-/gut-derived hormones to regulate food intake/body weight and hepatic glucose production/plasma glucose levels. Importantly, some of these CNS sensing mechanisms are disrupted in obesity and diabetes, leading to an elevation of blood glucose levels and body weight. One of the research programs in my laboratory is to elucidate novel nutrient-sensing mechanisms in the brain that regulate glucose and energy homeostasis. 

Gut nutrient-sensing mechanisms. It has been demonstrated that the central nervous system (via a gut-brain axis) plays an important role in lipid-sensing mechanisms in the gut to regulate food intake. In my laboratory, we have demonstrated that lipid-sensing mechanisms in the gut could also trigger a gut-brain-liver neuronal axis to regulate hepatic glucose production. In other words, lipid-sensing mechanisms could be triggered in the gut to remotely control the brain for regulation of hepatic glucose production. Our second research program is to elucidate novel nutrient-sensing mechanisms in the gut that could trigger the nervous system to regulate glucose and energy homeostasis.

Sample Publications: 

  • Breen D et al. A Duodenal PKC-delta and cholecystokinin signaling axis regulates glucose production Diabetes 60:3148-3153, 2011
  • Kokorovic A et al. Duodenal mucosal protein kinase C-delta regulates glucose production in rats Gastroenterology 141:1720-27, 2011
  • Lam TKT: China needs to boost funding for graduate students to stay competitive. Nat Med 17(6):655, 2011. (Live-interview at Nature Medicine Podcast: Time 17:42, TV interview)
  • Chari M et al. Glucose transporter-1 in the hypothalamic glial cells mediates glucose sensing to regulate glucose production in vivo. Diabetes 60:1901-06. 2011
  • Lam CKL et al. Hypothalamic nutrient sensing activates a forebrain-hindbrain neuronal circuit to regulate glucose production in vivo. Diabetes 60:107-13, 2011.
  • Yang CS et al. Hypothalamic AMPK regulates glucose production. Diabetes 59:2435-43, 2010.
  • Lam CKL et al. Activation of NMDA receptors in the dorsal vagal complex lowers glucose production. J Biol Chem 285:21913-21921, 2010.
  • Lam TKT. Neuronal regulation of homeostasis by nutrient sensing. Nat Med 16:392-395, 2010.
  • Cheung G et al. Intestinal cholecystokinin controls glucose production through a neuronal network. Cell Metab 10:99-109, 2009 (cover story, TV interview).
  • Ross R et al. Hypothalamic protein kinase C regulates glucose production. Diabetes 57:2061-2065, 2008.
  • 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).
  • Chari M et al. Activation of central lactate metabolism lowers glucose production in uncontrolled diabetes and diet-induced insulin resistance. Diabetes 57(4):836-40, 2008.
  • Caspi L et al. A balance of lipid-sensing mechanisms in the brain and liver. Cell Metab 2007 Aug;6(2):99-104.
  • Lam TKT et al. Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins. Nat Med 2007 Feb;13(2):171-80, 2007.
  • Lam TKT et al. Regulation of blood glucose by hypothalamic pyruvate metabolism. Science 309(5736):943, 2005.
  • Lam TKT et al. Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis homeostasis. Nat Med 11(3): 320, 2005.