Aqueous Extracts of Pancreas

Murlin, John R.; Clough, Harry D.; Gibbs, C. B. F.; Stokes, Arthur M.

doi:10.1016/s0021-9258(18)85619-8

Cited by 122 publications

(14 citation statements)

References 14 publications

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“…The application of proglucagon-derived peptides (PGDPs) in the management of conditions such as T2DM represents the pinnacle of a remarkable story in peptide discovery and rational drug design. It was shear perseverance which led to the elucidation of proglucagon almost six decades after that of glucagon (9,(11)(12)(13)(14)(15)(16). Rapid discoveries followed of GLP-1 and GLP-2 (15,16), both of which have been successfully exploited by peptide chemistry approaches to generate fully approved medications.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, a family of glucagon-related peptides exists, all of which are derived from differential processing of a common prohormone, proglucagon (8). Whilst glucagon and its hyperglycaemic actions were discovered in 1922 (9), its amino acid sequence was not elucidated until 1957 (10). Furthermore, proglucagon went undiscovered until the early 1980's, when its cDNA was initially identified in anglerfish (11,12), with discovery of a proglucagon equivalent in rat (13,14), hamster (15), cow and human several years later (16).…”

Section: Proglucagon -Discovery and Processingmentioning

confidence: 99%

“…Discovered shortly after insulin (9), glucagon and insulin are intrinsically linked, with the major metabolic actions of glucagon counteracting those of insulin (35). As such, insulin secretion from pancreatic beta-cells is stimulated largely by elevated glucose concentrations, reducing circulating glucose levels via inhibition of glycogenolysis and gluconeogenesis, accompanied by stimulation of glycogen synthesis in the liver (36).…”

Section: Glucagonmentioning

confidence: 99%

“…The hyperglycaemic action of glucagon is well-established, being demonstrated as early as its discovery, with the hormone's name reflecting this; glucagon -"the glucose agonist" (9). Hyperglycaemic actions of glucagon are mediated through promotion of glycogenolysis and gluconeogenesis in liver, whilst also inhibiting glycolysis and glycogenesis (41).…”

Section: Glucagonmentioning

confidence: 99%

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Proglucagon-Derived Peptides as Therapeutics

et al. 2021

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Initially discovered as an impurity in insulin preparations, our understanding of the hyperglycaemic hormone glucagon has evolved markedly over subsequent decades. With description of the precursor proglucagon, we now appreciate that glucagon was just the first proglucagon-derived peptide (PGDP) to be characterised. Other bioactive members of the PGDP family include glucagon-like peptides -1 and -2 (GLP-1 and GLP-2), oxyntomodulin (OXM), glicentin and glicentin-related pancreatic peptide (GRPP), with these being produced via tissue-specific processing of proglucagon by the prohormone convertase (PC) enzymes, PC1/3 and PC2. PGDP peptides exert unique physiological effects that influence metabolism and energy regulation, which has witnessed several of them exploited in the form of long-acting, enzymatically resistant analogues for treatment of various pathologies. As such, intramuscular glucagon is well established in rescue of hypoglycaemia, while GLP-2 analogues are indicated in the management of short bowel syndrome. Furthermore, since approval of the first GLP-1 mimetic for the management of Type 2 diabetes mellitus (T2DM) in 2005, GLP-1 therapeutics have become a mainstay of T2DM management due to multifaceted and sustainable improvements in glycaemia, appetite control and weight loss. More recently, longer-acting PGDP therapeutics have been developed, while newfound benefits on cardioprotection, bone health, renal and liver function and cognition have been uncovered. In the present article, we discuss the physiology of PGDP peptides and their therapeutic applications, with a focus on successful design of analogues including dual and triple PGDP receptor agonists currently in clinical development.

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Section: Discussionmentioning

confidence: 99%

Section: Proglucagon -Discovery and Processingmentioning

confidence: 99%

Section: Glucagonmentioning

confidence: 99%

Section: Glucagonmentioning

confidence: 99%

See 2 more Smart Citations

Proglucagon-Derived Peptides as Therapeutics

et al. 2021

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“…Im Jahre 1923 beobachteten M u r 1 j n und seine Mitarbeiter, daß manche Insulin-Präparate neben dem blutzuckersenkenden auch ein blutzuckersteigerndes Prinzip enthalten (1). Sie nannten es Glukagon.…”

Section: Ubersicht Der Schriftleitung Glukagonunclassified