Leon S. Farhi

Associate Professor of Research, Medicine- Endocrinology and Metabolism

Primary Location

UVA Division of Endocrinology & Metabolism
PO Box 801405
Charlottesville, VA 22908

Primary Phone Number

434.924.2496

[email protected]

Website

http://www.people.virginia.edu/~lsf8n

Bio & Overview

My research is in the field of systems endocrinology and focuses on the endocrine mechanisms and relationships between the different cell types in the islets of Langerhans that direct the time-varying secretion patterns of the pancreatic hormones. We are interested in the mechanisms of glucagon release from the α-cells in response to hypoglycemia, study how these mechanisms are altered in diabetes, and seek to develop strategies for their repair. Through series of interdisciplinary experimental and clinical in vivo work and mathematical modeling in silico studies, we have shown that the abnormalities in the glucagon defenses against hypoglycemia in diabetes are mediated in part by miscommunication between the different cell types in the pancreatic islets and are essentially of "network origin". The lack of β-cell signaling is the primary deficiency that contributes to two separate network defects: (i) absence of a "switch-off" trigger to the α-cells and (ii) increased intraislet basal glucagon. We have experimental evidence suggesting that both defects can be potentially repaired by therapeutic strategies based on the use of α-cell inhibiting drugs. To further test the hypothesis that α-cell inhibitors can be used to manipulate the pancreatic network to enhance the glucagon response to hypoglycemia and start translation of our findings into the clinic our lab collaborates with the UVA Center for Diabetes Technology. Taking advantage of the Center's cutting-edge artificial pancreas technologies we work on the development of strategies for dual-hormone automated glucose control in patients with type 1 diabetes that use both insulin and α-cell inhibiting drugs. The addition of an α-cell inhibitor as a second control mechanism is expected to allow us to manipulate the pancreatic endocrine network to achieve better glycemic control with reduced hypoglycemia risk.

Academic Information

Department: Medicine- Endocrinology and Metabolism

Academic Title: Associate Professor

Other Affiliations

BIMS

Research Interests

Understanding the mechanisms that regulate glucagon secretion, glucose homeostasis, and growth hormone release. Mathematical modeling of hormone networks. Diabetes, hypoglycemia, artificial pancreas technology.

Selected Publications

Farhy LS, McCall AL, Glucagon - the new 'insulin' in the pathophysiology of diabetes., 2015; Current opinion in clinical nutrition and metabolic care. 18(4) 407-14. PMID: 26049639

Gaylinn BD, Farhy LS, Nass R, Tong J, Thorner MO, Does des-acyl ghrelin improve glycemic control by decreasing acylated ghrelin levels?, 2015; European journal of endocrinology / European Federation of Endocrine Societies. 173(1) L1-2. PMID: 26026595

Nass R, Nikolayev A, Liu J, Pezzoli SS, Farhy LS, Patrie J, Gaylinn BD, Heiman M, Thorner MO, The level of circulating octanoate does not predict ghrelin O-acyl transferase (GOAT)-mediated acylation of ghrelin during fasting., 2014; The Journal of clinical endocrinology and metabolism. 100(1) E110-3. PMID: 25337923 | PMCID: PMC4283022

Nass R, Liu J, Patrie J, Pezzoli SS, Farhy LS, Gaylinn BD, Thorner MO, Four-hour infusion of hydrocortisone does not suppress the nocturnal increase of circulating acyl- or desacyl-ghrelin concentrations in healthy young adults., 2014; The Journal of clinical endocrinology and metabolism. 99(9) E1696-700. PMID: 24963646 | PMCID: PMC4154104

Nass R, Farhy LS, Liu J, Pezzoli SS, Johnson ML, Gaylinn BD, Thorner MO, Age-dependent decline in acyl-ghrelin concentrations and reduced association of acyl-ghrelin and growth hormone in healthy older adults., 2013; The Journal of clinical endocrinology and metabolism. 99(2) 602-8. PMID: 24285677 | PMCID: PMC3913814

Lv D, Breton MD, Farhy LS, Pharmacokinetics modeling of exogenous glucagon in type 1 diabetes mellitus patients., 2013; Diabetes technology & therapeutics. 15(11) 935-41. PMID: 23978267 | PMCID: PMC3818836

McCall AL, Farhy LS, Treating type 1 diabetes: from strategies for insulin delivery to dual hormonal control., 2013; Minerva endocrinologica. 38(2) 145-63. PMID: 23732369 | PMCID: PMC4220674

Farhy LS, Chan A, Breton MD, Anderson SM, Kovatchev BP, McCall AL, Association of Basal hyperglucagonemia with impaired glucagon counterregulation in type 1 diabetes., 2012; Frontiers in physiology. 3() 40. PMID: 22403550 | PMCID: PMC3288769

Farhy LS, Ortiz EA, Kovatchev BP, Mora AG, Wolf SE, Wade CE, Average daily risk range as a measure of glycemic risk is associated with mortality in the intensive care unit: a retrospective study in a burn intensive care unit., 2011; Journal of diabetes science and technology. 5(5) 1087-98. PMID: 22027301 | PMCID: PMC3208864

Farhy LS, McCall AL, Optimizing reduction in basal hyperglucagonaemia to repair defective glucagon counterregulation in insulin deficiency., 2011; Diabetes, obesity & metabolism. 13() 133-43. PMID: 21824267 | PMCID: PMC3289058