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Scientist Division of Cellular & Molecular Biology Toronto General Research Institute (TGRI) |
Keywords: diabetes, obesity, insulin action, nutrient sensing, artheroschlerosis
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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. The disruption of this homeostasis is partly caused 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 reveal new therapeutic molecules that could be targeted to restore glucose and energy homeostasis in diabetes and obesity.
Brain nutrient-sensing mechanisms
The central nervous system -- or more specifically, the hypothalamus -- has received much attention in recent diabetes and obesity research. This is based on the fact that the hypothalamus can 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 to regulate food intake. In my laboratory, we have demonstrated that lipid-sensing mechanisms can be triggered in the gut to remotely control the regulation of hepatic glucose production through the brain. Our second research program is to elucidate novel nutrient-sensing mechanisms in the gut that can trigger the nervous system to regulate glucose and energy homeostasis.
Additional Appointments
- John Kitson McIvor (1915-1942) Chair in Diabetes Research
- Canada Research Chair in Obesity
- Associate Professor of Physiology and Medicine, University of Toronto
- Division of Endocrinology, University Health Network & Mount Sinai Hospital
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Selected Publications | - Lam CKL et al. Activation of NMDA receptors in the dorsal vagal complex lowers glucose production. J Biol Chem (epub May 6, 2010).
- 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).
- 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. Epub Jan 9, 2008.
- Caspi L et al. A balance of lipid-sensing mechanisms in the brain and liver. Cell Metabolism 2007 Aug;6(2):99-104.
- Lam TKT et. al. Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins. Nature Medicine 2007 Feb;13(2):171-80. Epub Feb 4, 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. Nature Medicine 11(3): 320, 2005. Epub Feb 27, 2005.
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Primary Office MaRS Centre Toronto Medical Discovery Tower 10th Floor Rm 10-705 101 College Street Toronto, Ontario Canada M5G 1L7Primary Lab MaRS Centre Toronto Medical Discovery Tower 10th Floor Rm 10-601 101 College Street Toronto, Ontario Canada M5G 1L7 Additional Toronto General Hospital Max Bell Research Centre 4th Floor Rm 4MBRC406-Res 11 200 Elizabeth St. Toronto, Ontario Canada M5G 2C4 |
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| 416-581-7880 | (Primary) | | 416-581-7697 | (LAB) | | 416-581-7697 | (FAX) |
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| Carol Lam | | Clair Yang | | Madhu Chari | | Penny Wang | | Katie Lee | | Teresa (Yeuk Yu) Lai | | Andrea Kokorovic | | Becky Koscik | | Grace Cheung |
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