Deciphering Metabolic Messages From the Gut Drives Therapeutic Innovation: The 2014 Banting Lecture
Bibliographic record
Abstract
The Banting Medal for Scientific Achievement is the highest scientific award of the American Diabetes Association (ADA). Given in memory of Sir Frederick Banting, one of the key investigators in the discovery of insulin, the Banting Medal is awarded annually for scientific excellence, recognizing significant long-term contributions to the understanding, treatment, or prevention of diabetes. Daniel J. Drucker, MD, of the Department of Medicine, Mount Sinai Hospital and the Lunenfeld-Tanenbaum Research Institute in Toronto, Ontario, Canada, received the prestigious award at the ADA's 74th Scientific Sessions, 13-17 June 2014, in San Francisco, California. He presented the Banting Lecture, "Deciphering Metabolic Messages From the Gut Drives Therapeutic Innovation," on Sunday, 15 June 2014.Gut peptides convey nutrient-regulated signals to the enteric nervous system and to distal organs, acting as circulating hormones secreted in the basal and postprandial state. Here I provide an overview of the actions of glucagon-like peptide (GLP)-1 and GLP-2, the two major enteroendocrine L-cell peptides. The endogenous physiological actions of GLP-1 have been delineated using antagonists and Glp1r(-/-) mice and include the control of islet hormone secretion in a glucose-dependent manner, leading to improvement of fasting and postprandial glucose homeostasis. GLP-1 receptors (GLP-1Rs) are also widely distributed in multiple extrapancreatic organs, providing a mechanistic explanation for the nonglycemic actions attributed to GLP-1. The multiple metabolic actions of GLP-1 enable reduction of glycemia and body weight in diabetic and obese subjects, providing the opportunity to reduce glycemia in human subjects with diabetes with a low risk of hypoglycemia. GLP-2 plays a key role in the control of energy absorption and in the integrity of the intestinal mucosa, and a GLP-2R agonist, teduglutide, is now used for augmentation of energy absorption in parenteral nutrition-dependent subjects with short bowel syndrome. GLP-1 and GLP-2 are both cleaved by dipeptidyl peptidase-4 (DPP-4); hence, inhibition of DPP-4 activity enables yet another pathway for potentiation of incretin action and the therapy for type 2 diabetes. Here I review our 30-year experience with the elucidation of gut hormone action and, wherever possible, highlight therapeutic implications of our preclinical studies and future opportunities for incretin research.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.006 | 0.004 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.003 | 0.012 |
| Insufficient payload (model declined to judge) | 0.009 | 0.005 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".