W. Wayne Lautt
Professor Emeritus- Department of Pharmacology and Therapeutics
University of Manitoba
753 McDermot Avenue, Chown Building A210
Winnipeg, MB R3E 0T6
tel: (204) 789-3391 fax: (204) 975-7784
Email:   wlautt@cc.umanitoba.ca  

Research Focus:
We have recently discovered the mechanism of insulin resistance in type 2 diabetes and many other disease states.  The mechanism is activated only following a meal and results n meal-induced insulin sensitization with the postprandial response to insulin being doubled as a result.  This new mechanism is based upon the ability of insulin to cause the release of a hormone (hepatic insulin sensitizing substance (HISS)) from the liver that acts selectively on skeletal muscle to stimulate glucose uptake and storage as glycogen.  The ability of insulin to release HISS is dependent on two feeding signals delivered to the liver through the hepatic parasympathetic nerves and hepatic glutathione.  Dysfunction of the hepatic nerves leads to insulin resistance secondary to lack of HISS action and results in postprandial hyperglycemia, hyperinsulinemia, hypertriglyceridemia, increased free radical production, obesity, and type 2 diabetes.  Therapeutic approaches to treat diabetes are directed at mimicking or potentiating the feeding signals in order to restore insulin sensitivity.  These studies range from molecular to cellular to integrative animal to human studies and include corporate pharmaceutical development. 

Common Areas:
Liver integrative functions, vascular, neural, metabolic; diabetes, gestational diabetes, insulin resistance; cardiovascular autonomic nerve and metabolic dysfunctions in type 2 diabetes.

Current Research Areas:
1)  Regulation of insulin sensitivity in skeletal muscle by a hepatic factor released through a parasympathetic reflex. Related to insulin resistance in diabetes and other disease states.
2)  Drug discovery program to treat insulin resistance

General Research Approaches:
In vivo determination of neuro-humoral and cardiovascular responses in liver and splanchnic systems. Hepatic and whole body regulation of glucose metabolism. Autonomic nervous actions in vascular and metabolic regulation. The use of in vitro bioassays to detect endogenous regulators. Insulin sensitivity tests.
Awards:

Recent Publications:
Ming, Z., Legare, D.J., and Lautt, W.W. 2009. Obesity, syndrome X, and diabetes: the role of HISS-dependent insulin resistance altered by sucrose, an antioxidant cocktail, and age. Can. J. Physiol. Pharmacol. (in press)

Lautt, W.W. and Ming Z. 2009. Use of an antioxidant cocktail for insulin resistance associated with age and a high sugar diet: a hepatic mechanism. In: Nutrition, Diet Therapy, and the Liver. Eds: V.R. Preedy, R. Srirajaskanthan, R. Lakshman, and R.R. Watson. Taylor and Francis, CRC Press, London, Chapter 21, pp.319-333. 

Patarrao, R.S., Lautt, W.W., Guarino, M.P., Afonso, R.A., Ribeiro, R.T.,   Fernandes, A.B., Boavida, J.M., and Macedo, M.P. 2008. Meal-induced insulin sensitization (MIS) and its parasympathetic regulation in humans. Can. J. Physiol. Pharmacol. 86: 880-888.

Lautt, W.W., Ming, Z., Macedo, M.P. and Legare, D.J. 2008. HISS-dependent insulin resistance (HDIR) in aged rats is associated with adiposity, progresses to syndrome X, and is attenuated by a unique antioxidant cocktail. Exp. Gerontol. 43: 790-800.

Taylor, W.A., Legare, D., Lautt, W.W., and Hatch, G.M. 2007. Regulation of cardiac mitochondrial monolysocardiolipin acyltransferase activity and expression during development and in fetal alcohol syndrome. Proc. West. Pharmacol. Soc. 50: 115-118.

Patarrao, R.S., Lautt, W.W., Guarino, M.P., Afonso, R.A., Ribeiro, R.T., Fernandes, A.B., Boavida, J.M., and Macedo, M.P. 2007. A new technique to assess insulin sensitivity in humans: the rapid insulin sensitivity test (RIST). Proc. West. Pharmacol. Soc. 50 105-109.

Lautt, W.W. 2007. Postprandial insulin resistance as an early predictive cardiovascular risk factor. Therap. Clin. Risk Managem. 3: 761-770, 2007

Lautt, W.W. 2007. Regulatory processes interacting to maintain hepatic blood flow constancy: vascular compliance, hepatic arterial buffer response, hepatorenal reflex, liver regeneration, escape from vasoconstriction.    Hepatology Research 37: 891-903, 2007

Afonso, R.A., Lautt, W.W., Ribeiro, R.T., Legare, D.J., and Macedo, M.P. 2007. Insulin resistance in two animal models of obesity: a comparison of HISS-dependent and HISS-independent insulin action in high-fat diet-fed and Zucker rats.  Proc. West. Pharmacol. Soc. 50: 110-114.

Sadri, P., Reid, M.A.G., Afonso, R.A., Schafer, J., Legare, D.J., Macedo, M.P. and Lautt, W.W. 2006. Meal-induced insulin sensitization in conscious and anesthetized rat models comparing liquid mixed meal with glucose and sucrose. Br. J. Nutr. 94: 1-8.

Ming, Z., Fan, Y-J., Yang, X., and Lautt, W.W. 2006. Synergistic protection by S-adenosylmethionine with vitamins C and E on liver injury induced by thioacetamide in rats. Free Rad. Biol. Med. 40: 617-624.

Ting, J.W. and Lautt, W.W. 2006. The effect of acute, chronic, and prenatal ethanol exposure on insulin sensitivity. Pharmacol. Therap. . 111: 346-373.

Schoen Smith, J.M. and Lautt, W.W. 2006. The role of nitric oxide and prostaglandins in potentiation of the liver regeneration cascade in the rat. Can. J. Gastroenterol.  20: 329-344Sadri, P., Reid, M.A.G., Afonso, R.A., Schafer, J., Legare, D.J., Macedo, M.P., and Lautt, W.W. 2006. Meal-induced insulin sensitization in conscious and anesthetized rat models comparing liquid mixed meal with glucose and sucrose. Br. J. Nutr. 95: 288-295.

Seredycz, L., Ming, Z., and Lautt, W.W. 2006. Acute hemorrhage causes hepatic insulin sensitizing substance (HISS)-dependent insulin resistance. Can. J. Physiol. Pharmacol. 84: 1145-1151.

Seredycz, L. and Lautt, W.W. 2006. Hemorrhage results in hepatic insulin sensitizing substance-dependent insulin resistance mediated by somatostatin in rats. Neuroendocrinology 84: 94-102.

Ming, Z. and Lautt, W.W. 2006. Intrahepatic adenosine-mediated activation of hepatorenal reflex is via A1 receptors in rats. Can. J. Physiol. Pharmacol. 84: 1177-1184.Ming, Z., Fan, Y-J., Yang, X., and Lautt, W.W. 2006. Contribution of hepatic adenosine A1 receptors to renal dysfunction associated with acute liver injury in rats. Hepatology 44: 813-822.

Ming, Z., Fan, Y-J., Yang, X., and Lautt, W.W. 2005. Blockade of intrahepatic adenosine receptors improves urine excretion in cirrhotic rats induced by thioacetamide.  J. Hepatology 42: 680-686.

Ribeiro, R.T., Lautt, W.W., Legare, D.J., and Macedo, M.P. 2005. Insulin resistance induced by sucrose-feeding is due to an impairment of the hepatic parasympathetic nerves. Diabetologia 48: 976-983.

Lautt, W.W., Legare, D.J., Reid, M.A.G., Sadri, P., Ting, J.W., and Prieditis, H. 2005. Alcohol suppresses meal-induced insulin sensitization (MIS). Metabolic Syndrome and Related Disorders 3: 51-59.

Lautt, W.W. 2005. Insulin sensitivity in skeletal muscle regulated by a hepatic hormone, HISS. Can. J. Appl. Physiol. 30(3): 304-312.

Sadri, P., Legare, D.J., Takayama, S., and Lautt, W.W. 2005.  Increased incidence of HISS-dependent insulin resistance in female rats prenatally exposed to ethanol. Can. J. Physiol. Pharmacol. 83: 383-387.

Schoen Smith, J.M. and Lautt, W.W. 2005. The role of prostaglandins in triggering the liver regeneration cascade. Nitric Oxide 13: 111-117.

Active Grant Funding:

CIHR Operating Grant 2007-2010 

“Impact of sucrose, exercise, and antioxidants on the progression from insulin resistance to diabetes and the metabolic syndrome in aging rats”

CIHR Operating Grant 2007-2010 
“Abnormal meal-induced insulin sensitization as a cause of cardiovascular disease in aged rats and in sucrose supplemented diets”

CIHR Regional Partnerships Program/Manitoba Health Research Council 2009-2011 

“Mechanism of loss of vasodilation response to insulin in type 2 diabetes”

Awards:
First Annual J.A.F. Stevenson Memorial Award presented by the Canadian Physiological Society for outstanding scientific contribution, 1980
Maharishi Award ‑ community recognition for scientific achievement, 1982
Outstanding Preclinical Medical Teaching Award, University of Saskatchewan, 1982
The Ciba-Geigy Canada Ltd. Prestigious Award for outstanding contributions to Pharmacology in Canada presented by the Pharmacological Society of Canada, 1995
Dr. R.E. Beamish Award for excellence in cardiovascular research presented by the Heart & Stroke Foundation of Manitoba, 1996
Dr. R.E. Beamish Award for excellence in cardiovascular research presented by the Heart & Stroke Foundation of Manitoba, 1999
Sigma Xi Senior Scientist Award, 1999
The 1998 Ernesto Roma Award for contribution to diabetes research presented by the Portuguese Diabetes Association, 1999
University of Manitoba Graduate Students= Teaching Award presented by the University Teaching Services, 1999
Dr. R.E. Beamish Award for excellence in cardiovascular research presented by the Heart & Stroke Foundation of Manitoba, 2002
Michael Smith Prize in Health Research Finalist for recognition and support of outstanding research presented by the Canadian Institutes of Health Research 2004-2006
The Hargreaves Prize for Clinical Studies in Diabetes Award to Rita Patarrao, M. Paula Macedo, and W. Wayne Lautt, 2006

Patents: