Table 1.
Some of the major milestones in the discovery, secretion and physiology of proglucagon-derived peptides with focus on pre-molecular biology era.
| Year | Author(s) | Milestone | Reference(s) |
|---|---|---|---|
| 1907 | Lane | Distinguished alpha- and beta-islet cells | (11) |
| 1923 | Collip | Commented on initial hyperglycaemic effect of pancreatic extracts | (12) |
| 1923 | Kimball/Murlin | Discovered and named glucagon | (13) |
| 1948 | Sutherland/de Duve | Identified enteroglucagon | (14) |
| 1956 | Bromer | Structural elucidation of glucagon | (15) |
| 1959 | Unger | Glucagon radioimmunoassay | (16) |
| 1962 | Hellman/Hellerström/Unger/Madison | Islet alpha-cells recognised as site glucagon synthesis | (17, 18) |
| 1962 | Marks/Samols | Insulin-releasing action of glucagon | (19, 20) |
| 1964 | McIntyre/Holsworth/Turner | Demonstrated enhanced insulin release with oral glucose – the incretin effect | (21) |
| 1965 | Marks/Samols | Feeding increases circulating GLI | (22) |
| 1967 | Samols/Marks | Circulating GLI persists in humans following pancreatectomy | (23) |
| 1970s | Valverde/Holst/Buchanan/Conlon | Heterogeneity of gut GLI, measurement of circulating GLI | (24–28) |
| 1970s | Unger/Gerich Grodsky | Elucidation of glucagon physiology | (29, 30) |
| 1972 | Bloom | Greater villus growth in enteroglucagonoma (presumably action of GLP-2) | (31) |
| 1973 | Tager/Steiner | Characterization of oxyntomodulin, namely proglucagon (33–69) | (32) |
| 1976 | Unger | Importance of glucagon in diabetes | (33) |
| 1982 | Lund/Habener/Bell | Molecular biology elucidates proglucagon gene: glucagon, GLP-1, GLP-2, glicentin oxyntomodulin, GRRP | (34–36) |
| 1987 | Holst/Mojsov/Weir | Cleavage of GLP-1 (1–37) to GLP-1 (7–36) and demonstration of its potent insulin releasing activity | (37, 38) |
| 1987 | Bloom | Physiological insulinotropic action GLP-1 in man | (39) |
| 1993 | Mentlein | Degradation of glucagon family peptides, including GLP-1 (7–36) in vitro by DPP-4 | (40) |
| 1990s | Holst/Nauck/ Drucker | Elucidation of GLP-1 physiology | (41–44) |
| 1994 | Steiner | Role of PC2 in proglucagon processing to glucagon in islet alpha-cells | (45) |
| 1995 | Deacon/Holst | GLP-1 (9–36) - major metabolite in man, opening way for use of DPP-4 inhibitors and stable forms of GLP-1 for diabetes therapy | (46) |
| 1996 | Brubaker | Role of PC1/3 in differential proglucagon processing gut | (47) |
| 1996 | Drucker | Trophic action of GLP-2 in gut – opening way for future therapeutic use of GLP-2 analogues in short bowel syndrome | (48) |
We acknowledge that many investigators have contributed to advances in research on proglucagon-derived peptides and we apologise for any obvious omissions. Interested readers are referred to several excellent reviews for detailed consideration of early work and the advances made after identification of the proglucagon gene: These include articles by Conlon, Holst, Drucker, Muller, Marks and their co-authors: 1,2,3,4,5,11,12,13. DPP-4, dipeptidyl peptidase 4; GLI, glucagon-like immunoreactivity; GLP-1, glucagon-like peptide 1; GLP-2, glucagon-like peptide 2; GRPP, glicentin-related pancreatic polypeptide; PC1/3, prohormone convertase 1/3; PC2, prohormone convertase 2.