Human Glucagon Research Articles

Glucagon biosynthesis in human pancreatic islets: preliminary evidence for a biosynthetic intermediate.

Viable pancreatic islets were isolated from the pancreas of humans using modifications of the collagenase digestion and Ficoll gradient techniques. Gel filtration of tissue extracts following islet incubation in the presence of 3H- tryptophan indicated that radioactivity becomes incorporated into at least two islet proteins. The larger of the two (LGI) has the approximate molecular size of proinsuiln and the smaller coelutes with glucagon as determined by column standardization. Radioimmunoassay of the gel filtration eluate for glucagon revealed that both molecules have glucagon immunoreactivity. Gel filtration in the presence of 8M urea did not alter the elution pattern of the LGI molecule. Polyacrylamide gel electrophoresis was performed on these glucagon immunoreactive molecules. The 3H radioactivity and the glucagon immunoreactivity of the smaller molecule were found to co-migrate electrophoretically with crystalline porcine glucagon and monodesamidoglucagon. With electrophoresis at high pH the electrophoretic mobility of the LGI molecule proved to be lower than that of glucagon. Partial tryptic degradation of the human LGI molecule yields 3H-tryptophan labeled products having charge and immunologic characteristics indistinguishable from porcine glucagon and monodesamidoglucagon. Although further investigation is indicatend may thus serve as a precursor or an intermediate in human glucagon biosynthesis.

Inhibition of pancreatic glucagon responses to arginine by somatostatin in normal man and in insulin-dependent diabetics.

Somatostatin, a recently synthesized hypothalamic peptide thought to represent growth hormone-release-inhibiting factor, has been previously shown to inhibit pancreatic glucagon secretion in species other than man. To determine whether somatostatin also inhibits human glucagon secretion, plasma glucagon responses during intravenous infusion of arginine alone (250 mg. per kilogram over twenty-five minutes) and in combination with synthetic cyclic somatostatin (20,μg. per minute) were compared in six normal and six insulin-dependent diabetic subjects. Somatostatin abolished glucagon responses to arginine in both groups, with plasma glucagon declining transiently below basal levels; this occurred despite the fact that the diabetic subjects had fasting hyperglucagonemia and exaggerated glucagon responses during control arginine infusions. In both groups plasma glucose rises seen after arginine were diminished during somatostatin infusions, and, in the normal subjects, insulin responses were also inhibited. These results demonstrate that somatostatin is a potent inhibitor of glucagon secretion in man. Accordingly, it may prove useful as an adjunct to insulin therapy in treatment of insulin-requiring diabetes mellitus.

The amino acid sequence of human glucagon

FEBS LettersVolume 21, Issue 3 p. 315-319 Full-length articleFree Access The amino acid sequence of human glucagon J. Thomsen, J. Thomsen The Danish Institute of Protein Chemistry, affiliated to the Danish Academy of Technical Sciences, Finsensvej 33, DK-2000, Copenhagen F, DenmarkSearch for more papers by this authorK. Kristiansen, K. Kristiansen The Danish Institute of Protein Chemistry, affiliated to the Danish Academy of Technical Sciences, Finsensvej 33, DK-2000, Copenhagen F, DenmarkSearch for more papers by this authorK. Brunfeldt, K. Brunfeldt The Danish Institute of Protein Chemistry, affiliated to the Danish Academy of Technical Sciences, Finsensvej 33, DK-2000, Copenhagen F, DenmarkSearch for more papers by this authorF. Sundby, F. Sundby Novo Research Institute Nordre Fasenvej 215, DK-2200, Copenhagen N, DenmarkSearch for more papers by this author J. Thomsen, J. Thomsen The Danish Institute of Protein Chemistry, affiliated to the Danish Academy of Technical Sciences, Finsensvej 33, DK-2000, Copenhagen F, DenmarkSearch for more papers by this authorK. Kristiansen, K. Kristiansen The Danish Institute of Protein Chemistry, affiliated to the Danish Academy of Technical Sciences, Finsensvej 33, DK-2000, Copenhagen F, DenmarkSearch for more papers by this authorK. Brunfeldt, K. Brunfeldt The Danish Institute of Protein Chemistry, affiliated to the Danish Academy of Technical Sciences, Finsensvej 33, DK-2000, Copenhagen F, DenmarkSearch for more papers by this authorF. Sundby, F. Sundby Novo Research Institute Nordre Fasenvej 215, DK-2200, Copenhagen N, DenmarkSearch for more papers by this author First published: April 01, 1972 https://doi.org/10.1016/0014-5793(72)80192-3Citations: 68AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References 1 W.W. Bromer, M.E. Boucher, J.E. Koffenberger Jr., J. Biol. Chem., 246, (1971), 2822– 2 W.W. Bromer, L.G. Sinn, O.K. Behrens, J.Am. Chem. Soc., 79, (1957), 2807– 3 F. Sundby, J. Markussen, Horm. Metab. Res., 3, (1971), 184– 4 M.J. Gordon, personal communication (1970). 5 H.D. Niall, J. Agr. Food Chem., 19, (1971), 638– 6 P. Edman, G. Begg, European J. Biochem., 1, (1967), 80– 7 S. Yamada, H.A. Itano, Biochim. Biophys. Acta, 130, (1966), 538– 8 P. Edman, S.B. Needleman Protein Sequence Determination (1970), Springer-Verlag Berlin, Heidelberg, New York 211– 9 L.K. Ramachandaran, B. Witkop, C.H.W. Hirs Methods in Enzymology XI, (1967), Academic Press New York and London 283– 10 R. Sauer, H.D. Niall, J.T. Potts Jr., Federation Proc., 29, (1970), 728– 11 B. Blombäck, M. Blombäck, B. Hessel, S. Iwanaga, Nature, 215, (1967), 1445– 12 W.A. Schroeder, C.H.W. Hirs Methods in Enzymology XI, (1967), Academic Press New York and London 445– 13 F. Sundby and J. Markussen, Horm. Metab. Res., in press. Citing Literature Volume21, Issue3April 01, 1972Pages 315-319 ReferencesRelatedInformation

SEPARATION OF HUMAN INSULIN, GLUCAGON AND OTHER PANCREATIC PROTEINS.

Purified human insulin and beef-pork glucagon were subjected to electrophoresis on cellulose acetate strips. Insulin was found to migrate rapidly towards the anode as a single band, while glucagon migrated slowly towards the anode in two distinct fractions. Virtually complete separation of the two hormones was achieved. Electrophoresis of acid alcohol extracts of human pancreas revealed eight positively migrating bands. By means of densitometric, radioisotopic, and radioimmunochemical technics, fraction 2 was identified as the insulin-bearing fraction, and the area of fractions 7 and 8 as the glucagonbearing region. By gel filtration substantial quantities of the unidentified extraneous proteins, which make up the bulk of the pancreatic extract, were removed, thereby providing purer samples for electrophoresis. The technic makes possible the rapid preparation of relatively pure samples of glucagon-free insulin and insulinfree glucagon from the pancreas of man and other species in quantities sufficient for laboratory studies. In addition, the characterization of the electrophoretic mobility of these hormones provides a new means by which they may be identified in unknown samples.