University of Toronto Logo - Physiology

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ACADEMIC STATUS

Departmental Status:   Professor Emeritus

Primary/Cross-appointments:   Medicine

Degrees: M.D. 1955; D.Sc. 1962.; M.D. ( honoris causa) Karolinska Institute, Stockholm; D.Sc ( honoris causa) University of Toronto, University of Saskatchewan, University of Zagreb, Croatia.

O.C., O.Ont, FRCP (C) 1986, FRSC 1997, FCAHS, Laureate of the Canadian Medical Hall of Fame, Honourary President of the International Academy of Sportology (Japan).

Affiliations: Member of the Endocrine Division, Toronto Hospital, Banting and Best Diabetes Centre; Adjunct Professor at the Karolinska Institute, Stockholm, Sweden; Faculty of Medicine, University of Zagreb.

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RESEARCH

Research Divisions: Endocrine and Diabetes Platform

Expertise

1. Using tracer methodology to measure glucose turnover out of steady-state. The role of hormones and metabolites to regulate metabolic fluxes in physiology and diabetes.
2. Extra-pancreatic glucagon.

Research Interests:

1. The mechanisms of exercise and stress on the prevention of metabolic syndrome and development of type 2 diabetes. Role of excessive cortisol release in diabetes.
2. Effect of antecedent stress and hypoglycemia on the responses of the hypothalamic-pituitary-adrenal axis (gene expression of brain stress hormones and their receptors), and counterregulation (counterregulatory hormones, glucose turnover, adrenal medullary enzymes) in models of type 1 diabetes.
3. Molecular mechanisms responsible for inadequate response of counterregulatory hormones during insulin-induced hypoglycemia.
4. Prevention of hypoglycemia in type 1 diabetics, using somatostatin receptor antagonists. Improvement of deficient glucagon, cortisol, and catecholamine responses.
5. Physiology and pathophysiology of pancreatic α-cell in type 1 and type 2 diabetes.

Keywords:  Diabetes, stress, hypoglycemia, antecedent hypoglycemia, prevention of hypoglycemia in diabetes, genetic expression of brain stress hormones, and glucocortioid and mineralocorticoid receptors, biosynthesis and release of pancreatic glucagon and somatostatin, hepatic glucose production..

Detailed Description: (related to “research interests” 3, 4, and 5)

Hypoglycemia is the most serious acute complication of insulin-treated diabetes, and repeated exposure may have serious long-term effects on health. The most important reason for increased incidence of hypoglycemia in diabetes is the gradual decrease of counterregulatory hormone responses to hypoglycemic stimulation. In addition, chronic hyperglycemia induces adaptations in hepatic glucose production and muscle glucose uptake. The defect in counterregulation is augmented when repeated episodes of hypoglycemia (antecedent hypoglycemia) are experienced. We are exploring the mechanisms by which counterregulation, glucose production and glucose utilization is altered in diabetes and following antecedent hypoglycemia. In brain or hypophysis we are studying in situ expression of stress hormones (corticotrophin-releasing hormone and pro-opiomelanocortin) and receptors for glucocorticoids and mineralocorticoids. In pancreas we study the expression of proglucagon and prosomatostatin, and glucagon and somatostatin concentration. Non-steady state glucose turnover is used to study the final responses (glucose production and utilization). In blood we study the responses of insulin, all counterregulatory hormones, glucose and selected substrates. We have a patent to prevent hypoglycemia in type 1 diabetes by using somatostatin receptor antagonists.

A summary of my research over the last 50 years was published by the American Journal of Physiology: Endocrinology Metabolism and can be found in Vranic M. Odyssey between Scylla and Charybdis through storms of carbohydrate metabolism and diabetes: a career retrospective. Am J Physiol Endocrinol Metab , 299: E849-E867, 2010.

Link to PubMed: http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=PureSearch&db=pubmed&term=(Vranic M[Author Name )

Within the Department of Physiology:
Herbert Gaisano (Dept of Medicine and Physiology)

Outside the Department of Physiology:
Michael Riddell (Kinesiology, York University)