Daniel J. Drucker

Last updated

Daniel Drucker

FRS , FRCPC , OC
Daniel Joshua Drucker FRS.jpg
Daniel Drucker at the Royal Society admissions day in London, July 2015
Born
Daniel Joshua Drucker

(1956-06-23) 23 June 1956 (age 67) [1]
Montreal, Quebec, Canada [1]
Alma mater University of Toronto (MD) [2]
Awards
Scientific career
Fields
Institutions
Website

Daniel Joshua Drucker (born 23 June 1956) [1] is a Canadian endocrinologist. A Fellow of the Royal Society, [3] he is a professor of medicine at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto. He is known for his research into intestinal hormones and their use in the treatment of diabetes, obesity, and other metabolic diseases, as well as intestinal failure. [4]

Contents

Early life and education

Drucker was born and grew up in Montreal, went to high school in Ottawa, and then enrolled at the University of Ottawa, studying science. [5] In 1976, he moved to Toronto, where he studied medicine at the University of Toronto, graduating in 1980. He completed his internship at Johns Hopkins Hospital (1980–81), and completed his internal medicine and endocrinology residencies at the University of Toronto (1980–84). [5]

Career

Beginning in 1984, Drucker worked as a research fellow at the Massachusetts General Hospital and Harvard Medical School. Drucker was funded by a Medical Research Council of Canada Centennial Fellowship to study molecular endocrinology with Professor Joel Habener. Drucker’s discoveries in Boston included the demonstration that proglucagon could be cleaved into multiple smaller glucagon-like peptides, including several distinct isoforms of GLP-1. [6] Along with Svetlana Mojsov, he then discovered that GLP-1(7-37) — a truncated form of GLP-1 identified previously by Mosjov as an incretin [7] — directly stimulated cyclic AMP formation, insulin secretion, and insulin gene expression; notably, it did so only when glucose levels were elevated. [8] [9] In 1987 he returned to Toronto, taking on the position of assistant professor of medicine at the University of Toronto and working as a staff doctor.

Early in his career, Drucker discovered that hormones in the gut play important roles in the onset and development of Type 2 diabetes. [5] Drucker, together with colleagues at Tufts Universities, filed multiple patents describing the utility of targeting the DPP-4 enzyme, and published studied demonstrating that genetic or chemical inactivation of DPP-4 prevented degradation of GLP-1 and GIP, supporting the development of DPP-4 inhibitors for the treatment of type 2 diabetes. [10] [11] Collectively, the body of work from multiple investigators and companies led to the development of two leading classes of diabetes medications: GLP-1 receptor agonists and DPP4 inhibitors. [5]

In 1996, Drucker was one of several investigators who demonstrated that GLP-1 reduced food intake in preclinical studies. Notably, the experiments in the Drucker lab demonstrated that this action of GLP-1 in the brain required the functional canonical GLP-1 receptor. [12] In 1996, he also discovered the effects the first biological actions for GLP-2, demonstrating that GLP-2 augmented crypt cell proliferation and expansion of the mucosal epithelium in the small bowel of mice and rats. [13] He subsequently identified and characterized a DPP-4-resistant molecule, teduglutide, [14] that was ultimately developed and approved for the treatment of short bowel syndrome in adults and children, a disorder in which fluids are poorly absorbed after resection of the small intestine. [5] [15]

Drucker joined the staff of the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in 2006. In 2008 he conducted studies aimed at the development and testing of long-acting version of the diabetes medication exenatide. [16] He later studied the long-term effects of related weight-loss medicines on bowel health. [17] Drucker has also played key roles in the identification of the cardioprotective mechanisms of GLP-1 action, [18] and has identified multiple mechanisms linking GLP-1 to the reduction of inflammation [19] [20] .

He is a Canada Research Chair at the University of Toronto.

Awards and honours

Drucker has received many national and international awards in recognition of his research accomplishments revealing the mechanisms of action and therapeutic potential of enteroendocrine hormones. These include the Prix Galien Canada for outstanding academic research (2008), the Donald F. Steiner Award for Outstanding Diabetes Research from the University of Chicago (2007), the Clinical Investigator Award from the Endocrine Society (2009), the Claude Bernard Prize from the European Association for the Study of Diabetes (2012), the Oon International Award and Lecture from the University of Cambridge (2014), the Banting Medal for Scientific Achievement from the American Diabetes Association (2014) the Manpei Suzuki Foundation International Prize for Diabetes (2014), and the Harold Hamm International Prize for Biomedical Research in Diabetes (2019). In 2021 he was awarded the Canada Gairdner International Award. [21] In 2023, he received the Wolf Prize in Medicine [22] and the VinFuture Prize. [23]

Drucker was named an Officer of the Order of Canada in 2015. [24] [25] He was elected a Fellow of the Royal Society (FRS) in 2015. [5] [3] and was elected to the National Academy of Medicine in 2023. [26]

Selected publications

Related Research Articles

Drugs used in diabetes treat diabetes mellitus by decreasing the glucose level in the blood. With the exception of insulin, most GLP receptor agonists, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and their selection depends on the nature of diabetes, age, and situation of the person, as well as other factors.

<span class="mw-page-title-main">Incretin</span> Group of gastrointestinal hormones

Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-glucose–dependent mechanism.

<span class="mw-page-title-main">Glucose-dependent insulinotropic polypeptide</span> Mammalian protein found in Homo sapiens

Glucose-dependent insulinotropic polypeptide, abbreviated as GIP, is an inhibiting hormone of the secretin family of hormones. While it is a weak inhibitor of gastric acid secretion, its main role, being an incretin, is to stimulate insulin secretion.

Enteroglucagon is a peptide hormone derived from preproglucagon. It is a gastrointestinal hormone, secreted from mucosal cells primarily of the colon and terminal ileum. It consists of 37 amino acids. Enteroglucagon is released when fats and glucose are present in the small intestine; which decrease the motility to allow sufficient time for these nutrients to be absorbed.

<span class="mw-page-title-main">Exenatide</span> Medication

Exenatide, sold under the brand name Byetta and Bydureon among others, is a medication used to treat diabetes mellitus type 2. It is used together with diet, exercise, and potentially other antidiabetic medication. It is a treatment option after metformin and sulfonylureas. It is given by injection under the skin twice daily or once weekly.

<span class="mw-page-title-main">Vildagliptin</span> Chemical compound

Vildagliptin, sold under the brand name Galvus and others, is an oral anti-hyperglycemic agent of the dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1 and GIP by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucagon release by the alpha cells of the islets of Langerhans in the pancreas.

<span class="mw-page-title-main">Dipeptidyl peptidase-4 inhibitor</span> Enzyme blocker and diabetes treatment drug

Inhibitors of dipeptidyl peptidase 4 are a class of oral hypoglycemics that block the enzyme dipeptidyl peptidase-4 (DPP-4). They can be used to treat diabetes mellitus type 2.

<span class="mw-page-title-main">Glucagon-like peptide-1</span> Gastrointestinal peptide hormone Involved in glucose homeostasis

Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.

<span class="mw-page-title-main">Glucagon-like peptide-1 receptor</span> Receptor activated by peptide hormone GLP-1

The glucagon-like peptide-1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) found on beta cells of the pancreas and on neurons of the brain. It is involved in the control of blood sugar level by enhancing insulin secretion. In humans it is synthesised by the gene GLP1R, which is present on chromosome 6. It is a member of the glucagon receptor family of GPCRs. GLP1R is composed of two domains, one extracellular (ECD) that binds the C-terminal helix of GLP-1, and one transmembrane (TMD) domain that binds the N-terminal region of GLP-1. In the TMD domain there is a fulcrum of polar residues that regulates the biased signaling of the receptor while the transmembrane helical boundaries and extracellular surface are a trigger for biased agonism.

<span class="mw-page-title-main">Gastric inhibitory polypeptide receptor</span> Protein-coding gene in the species Homo sapiens

Structures of GIPR human variant Sun, B., Kobilka, B.K., Sloop, K.W., Feng, D., Kobilka, T.S.

<span class="mw-page-title-main">Glucagon-like peptide-2 receptor</span> Protein-coding gene in the species Homo sapiens

Glucagon-like peptide-2 receptor (GLP-2R) is a protein that in human is encoded by the GLP2R gene located on chromosome 17.

<span class="mw-page-title-main">Liraglutide</span> Anti-diabetic medication

Liraglutide, sold under the brand names Victoza and Saxenda among others, is an anti-diabetic medication used to treat type 2 diabetes, and chronic obesity. It is a second-line therapy for diabetes following first-line therapy with metformin. Its effects on long-term health outcomes like heart disease and life expectancy are unclear. It is given by injection under the skin.

Albiglutide is a glucagon-like peptide-1 agonist drug marketed by GlaxoSmithKline (GSK) for treatment of type 2 diabetes. As of 2017 it is unclear if it affects a person's risk of death. GSK has announced that it intends to withdraw the drug from the worldwide market by July 2018 for economic reasons.

Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 analogs, GLP-1DAs or incretin mimetics, are a class of drugs that reduce blood sugar and energy intake by activating the GLP-1 receptor. They mimic the actions of the endogenous incretin hormone GLP-1 that is released by the gut after eating.

<span class="mw-page-title-main">Dulaglutide</span> Diabetes medication

Dulaglutide, sold under the brand name Trulicity among others, is a medication used for the treatment of type 2 diabetes in combination with diet and exercise. It is also approved in the United States for the reduction of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. It is a once-weekly injection.

<span class="mw-page-title-main">Omarigliptin</span> Chemical compound

Omarigliptin (MK-3102) is a potent, long-acting oral antidiabetic drug of the DPP-4 inhibitor class used for once-weekly treatment of type 2 diabetes and currently under development by Merck & Co. It inhibits DPP-4 to increase incretin levels, which inhibit glucagon release, which in turn increases insulin secretion, decreases gastric emptying and decreases blood glucose levels.

Joel Habener is a Professor of Medicine at Harvard Medical School.

Svetlana Mojsov is a Serbian chemist who is a research associate professor at Rockefeller University. Her research considers peptide synthesis. She discovered the glucagon-like peptide-1 and uncovered its role in glucose metabolism and the secretion of insulin. Her breakthroughs were transformed by Novo Nordisk into therapeutic agents against diabetes and obesity.

Glucagon receptor agonists are a class of drugs under development for the treatment of obesity, non-alcoholic fatty liver disease, and congenital hyperinsulinism.

GLP1 poly-agonist peptides are a class of drugs that activate multiple peptide hormone receptors including the glucagon-like peptide-1 (GLP-1) receptor. These drugs are developed for the same indications as GLP-1 receptor agonists—especially obesity, type 2 diabetes, and non-alcoholic fatty liver disease. They are expected to provide superior efficacy with fewer adverse effects compared to GLP-1 mono-agonists, which are dose-limited by gastrointestinal disturbances. The effectiveness of multi-receptor agonists could possibly equal or exceed that of bariatric surgery. The first such drug to receive approval is tirzepatide, a dual agonist of GLP-1 and GIP receptors.

References

  1. 1 2 3 "DRUCKER, Prof. Daniel Joshua" . Who's Who . Vol. 2016 (online Oxford University Press  ed.). Oxford: A & C Black.(Subscription or UK public library membership required.)
  2. ↑ "Daniel J. Drucker M.D, FRCPC, Clinical Advisor, Diartis Pharmaceuticals, Inc". Bloomberg L.P. 16 February 2024.
  3. 1 2 3 "Professor Daniel Drucker FRS". London: The Royal Society. Archived from the original on 2 May 2015.
  4. ↑ "This Toronto doctor is a superstar in the world of diabetes research — and he says it all started as a fluke". Toronto Star , By Joseph Hall, 7 February 2020
  5. 1 2 3 4 5 6 Anon (2015). "Professor Daniel Drucker FRS". London: royalsociety.org. Archived from the original on 17 November 2015.
  6. ↑ Drucker, D J; Mojsov, S; Habener, J F (July 1986). "Cell-specific post-translational processing of preproglucagon expressed from a metallothionein-glucagon fusion gene". Journal of Biological Chemistry. 261 (21): 9637–9643. doi: 10.1016/s0021-9258(18)67561-1 . ISSN   0021-9258. PMID   3525530.
  7. ↑ Mojsov, S; Weir, G C; Habener, J F (1 February 1987). "Insulinotropin: glucagon-like peptide I (7-37) co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas". Journal of Clinical Investigation. 79 (2): 616–619. doi:10.1172/JCI112855. ISSN   0021-9738. PMC   424143 . PMID   3543057.
  8. ↑ Drucker, D J; Philippe, J; Mojsov, S; Chick, W L; Habener, J F (May 1987). "Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line". Proceedings of the National Academy of Sciences. 84 (10): 3434–3438. Bibcode:1987PNAS...84.3434D. doi: 10.1073/pnas.84.10.3434 . ISSN   0027-8424. PMC   304885 . PMID   3033647.
  9. ↑ O’Rahilly, Stephen (15 April 2021). "The islet's bridesmaid becomes the bride: Proglucagon-derived peptides deliver transformative therapies". Cell. 184 (8): 1945–1948. doi: 10.1016/j.cell.2021.03.019 . ISSN   0092-8674. PMID   33831374. S2CID   233131461.
  10. ↑ Marguet, Didier; Baggio, Laurie; Kobayashi, Takashi; Bernard, Anne-Marie; Pierres, Michel; Nielsen, Per F.; Ribel, Ulla; Watanabe, Takeshi; Drucker, Daniel J.; Wagtmann, Nicolai (6 June 2000). "Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26". Proceedings of the National Academy of Sciences. 97 (12): 6874–6879. Bibcode:2000PNAS...97.6874M. doi: 10.1073/pnas.120069197 . ISSN   0027-8424. PMC   18768 . PMID   10823914.
  11. ↑ Hansotia, Tanya; Baggio, Laurie L.; Delmeire, Dominique; Hinke, Simon A.; Yamada, Yuichiro; Tsukiyama, Katsushi; Seino, Yutaka; Holst, Jens J.; Schuit, Frans; Drucker, D.J. (1 May 2004). "Double Incretin Receptor Knockout (DIRKO) Mice Reveal an Essential Role for the Enteroinsular Axis in Transducing the Glucoregulatory Actions of DPP-IV Inhibitors". Diabetes. 53 (5): 1326–1335. doi:10.2337/diabetes.53.5.1326. ISSN   0012-1797. PMID   15111503.
  12. ↑ Scrocchi, L.A.; Brown, T.J.; Maclusky, N.; Brubaker, P.L.; Auerbach, A.B.; Joyner, A.L.; Drucker, D.J. (November 1996). "Glucose intolerance but normal satiety in mice with a null mutation in the glucagon–like peptide 1 receptor gene". Nature Medicine. 2 (11): 1254–1258. doi:10.1038/nm1196-1254. ISSN   1078-8956. PMID   8898756. S2CID   41872654.
  13. ↑ Drucker, D J; Erlich, P; Asa, S L; Brubaker, P L (23 July 1996). "Induction of intestinal epithelial proliferation by glucagon-like peptide 2". Proceedings of the National Academy of Sciences. 93 (15): 7911–7916. Bibcode:1996PNAS...93.7911D. doi: 10.1073/pnas.93.15.7911 . ISSN   0027-8424. PMC   38848 . PMID   8755576.
  14. ↑ Drucker, Daniel J.; Shi, Qing; Crivici, Anna; Sumner-Smith, Martin; Tavares, Wendy; Hill, Mary; DeForest, Lorraine; Cooper, Sari; Brubaker, Patricia L. (July 1997). "Regulation of the biological activity of glucagon-like peptide 2 in vivo by dipeptidyl peptidase IV". Nature Biotechnology. 15 (7): 673–677. doi:10.1038/nbt0797-673. ISSN   1087-0156. PMID   9219272. S2CID   35172107.
  15. ↑ "Toronto endocrinologist named 2018 Principal Award winner by Manning Foundation". The Globe and Mail, Allan Maki, Calgary, 2 October 201
  16. ↑ "Study: Once-a-week diabetes drug works better than twice-daily injection". Scientific American News Blog, By Susannah F. Locke on 8 September 2008
  17. ↑ "Researchers investigate possible colon cancer risk for new generation of weight-loss drugs".Science News, 3 March 2015
  18. ↑ Noyan-Ashraf, Mohammad Hossein; Momen, M. Abdul; Ban, Kiwon; Sadi, Al-Muktafi; Zhou, Yu-Qing; Riazi, Ali M.; Baggio, Laurie L.; Henkelman, R. Mark; Husain, Mansoor; Drucker, Daniel J. (1 April 2009). "GLP-1R Agonist Liraglutide Activates Cytoprotective Pathways and Improves Outcomes After Experimental Myocardial Infarction in Mice". Diabetes. 58 (4): 975–983. doi:10.2337/db08-1193. ISSN   0012-1797. PMC   2661586 . PMID   19151200.
  19. ↑ Wong, Chi Kin; Yusta, Bernardo; Koehler, Jacqueline A.; Baggio, Laurie L.; McLean, Brent A.; Matthews, Dianne; Seeley, Randy J.; Drucker, Daniel J. (October 2022). "Divergent roles for the gut intraepithelial lymphocyte GLP-1R in control of metabolism, microbiota, and T cell-induced inflammation". Cell Metabolism. 34 (10): 1514–1531.e7. doi: 10.1016/j.cmet.2022.08.003 . PMID   36027914.
  20. ↑ Wong, Chi Kin; McLean, Brent A.; Baggio, Laurie L.; Koehler, Jacqueline A.; Hammoud, Rola; Rittig, Nikolaj; Yabut, Julian M.; Seeley, Randy J.; Brown, Theodore J.; Drucker, Daniel J. (January 2024). "Central glucagon-like peptide 1 receptor activation inhibits Toll-like receptor agonist-induced inflammation". Cell Metabolism. 36 (1): 130–143.e5. doi:10.1016/j.cmet.2023.11.009. PMID   38113888. S2CID   266371336.
  21. ↑ Canada Gairdner International Award 2021
  22. ↑ Wolf Prize in Medicine 2023
  23. ↑ Nhu, Quynh (21 December 2023). "Battery researchers win $3M Vietnamese awards". VnExpress .
  24. ↑ "Order of Canada ceremony invests 48 new recipients, including NBA star Steve Nash". CBC News, 13 May 2016
  25. ↑ "Four Nova Scotians among Order of Canada honourees". The Chronicle-Herald , 1 July 2015.
  26. ↑ "National Academy of Medicine Elects 100 New Members". National Academy of Medicine. 9 October 2023. Retrieved 9 October 2023.
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