Summary
In normal fasting dog serum, the insulin: proinsulin molar proportion was 71:29%. In response to glucose infusion, the proinsulin proportion decreased. In the pancreas, the proinsulin proportion was lower than in serum. Growth hormone treatment for one day increased serum insulin sevenfold and proinsulin 18-fold. The proinsulin proportion increased to 49%. The growth hormone injections magnified the response to glucose infusion. The rise in serum insulin was 16 times the normal, proinsulin also rose but its proportion decreased. Growth hormone treatment for 6 days decreased pancreatic insulin to 5% and proinsulin to 46% of normal. In the permanent (metasomatotrophic) diabetes produced by the prolonged administration of growth hormone, serum insulin decreased and the proinsulin proportion increased. No rises in serum insulin nor proinsulin occurred following glucose infusion. In the pancreas, insulin and proinsulin were reduced to 1.6% and 8% of normal. The reduction in the immunoreactive insulin of the pancreas was more pronounced in the tail than in the head and body regions. The results indicate that in the state of augmented insulin secretion and hyperinsulinaemia produced by growth hormone and in the reduced insulin secretion and hypoinsulinaemia of metasomatotrophic diabetes, the proportion of proinsulin in serum is increased due to beta cell secretion containing a higher proportion of proinsulin than normal.
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Rubenstein AH, Melani F, Steiner DF (1972) Circulating proinsulin: immunology, measurement, and biological activity. In: Steiner DF, Freinkel N (eds) Handbook of physiology, Section 7, Endocrinology, vol 1, Endocrine Pancreas. American Physiological Society, Washington DC pp 515–528
Heding LG, Larsen UD, Markussen J, Jørgensen KH, Hallund O (1974) Radioimmunoassays for human, pork and ox C-peptides and related substances. Horm Metab Res (Suppl) 5:40–44
Horwitz DL, Starr JJ, Mako ME, Blackard WG, Rubenstein AH (1975) Proinsulin, insulin, and C-peptide concentrations in human portal and peripheral blood. J Clin Invest 55:1278–1283
Melani F, Rubenstein AH, Steiner DF (1970) Human serum proinsulin. J Clin Invest 49:497–507
Gorden P, Sherman B, Roth J (1971) Proinsulin-like component of circulating insulin in the basal state and in patients and hamsters with islet cell tumors. J Clin Invest 50:2113–2122
Gutman RA, Lazarus NR, Penhos JC, Fajans S, Recant L (1971) Circulating proinsulin-like material in functioning insulinomas. N Engl J Med 284:1003–1008
Sherman BM, Pek S, Fajans SS, Floyd JC Jr, Conn JW (1972) Plasma proinsulin in patients with functioning pancreatic islet cell tumors. J Clin Endocrinol Metab 35:271–280
Creutzfeldt W, Creutzfeldt C, Frerichs H, Track NS, Arnold R (1976) Histochemistry, ultrastructure and hormone content of human insulinomas. Horm Metab Res (Suppl) 6:7–18
Track NS, Frerichs H, Creutzfeldt W (1974) Release of newly synthesized proinsulin and insulin from granulated and degranulated isolated rat pancreatic islets. The effect of high glucose concentration. Horm Metab Res (Suppl) 5:97–103
Gorden P, Hendricks CM, Roth J (1974) Circulating proinsulin-like component in man: increased proportion in hypoinsulinemic patients. Diabetologia 10:469–474
Burgham GA, Etteldorf JW, Trouy RL, Kitabchi AE, Keslensky S (1976) Insulin and proinsulin in normal and chemical diabetic children. J Pediatr 89:48–53
Mako ME, Starr JI, Rubenstein AH (1977) Circulating proinsulin in patients with maturity onset diabetes. Am J Med 63:865–869
Heding LG (1977) Specific and direct radioimmunoassay for human proinsulin in serum. Diabetologia 13:467–474
Rainbow SJ, Woodhead JS, Yue DK, Luzio SD, Hales CN (1979) Measurement of human proinsulin by an indirect two-site immunoradiometric assay. Diabetologia 17:229–234
Luft R, Cerasi E, Werner S (1969) The effect of moderate and high doses of human growth hormone on the insulin response to glucose infusion in prediabetic subjects. Horm Metab Res 1:111–115
Pek S, Fajans SS, Floyd JC Jr, Knopf RF (1974) Clinical conditions associated with elevated plasma levels of glucagon. In: Malaisse WJ, Priart J, Vallance-Owen J (eds) Excerpta Medica, Int Congr Ser 312:207–213
Whittaker PG, Taylor KW (1980) Direct effects of growth hormone on rat islets of Langerhans in tissue culture. Diabetologia 18:323–328
Sirek A, Vranic M, Sirek OV, Vigas M, Policova Z (1979) Effect of growth hormone on acute glucagon and insulin release. Am J Physiol 237:E107-E112
Pierluissi J, Pierluissi R, Ashcroft SJH (1980) Effects of growth hormone on insulin release in the rat. Diabetologia 19:391–396
Pierluissi J, Campbell J (1980) Metasomatotrophic diabetes and its induction: basal insulin secretion and insulin release responses to glucose, glucagon, arginine and meals. Diabetologia 18:223–228
Campbell J, Pierluissi J, Green GR (1978) Somatotrophic diabetes: insulin release responses to arginine and glucagon in dogs. Diabetologia 15:205:-212
Davoreen PR (1962) The isolation of insulin from a single cat pancreas. Biochim Biophys Acta 63:150–153
Campbell J, Rastogi KS (1968) Elevation in serum insulin, albumin, and FFA, with gains in liver lipid and protein, induced by glucocorticoid treatment in dogs. Can J Physiol Pharmacol 46:421–429
Hunter WM, Greenwood FC (1962) Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature 194:495–496
Davis BJ (1964) Disc electrophoresis. II. Method and application to human serum proteins. Ann NY Acad Sci 121:404–427
Hales CN, Randle PJ (1963) Immunoassay of insulin with insulin-antibody precipitate. Biochem J 88:137–146
Chance RE, Ellis RM, Bromer WW (1968) Porcine proinsulin: characterization and amino acid sequence. Science 161:165–167
Yanaihara N, Yanaihara C, Sakagami M, Sakura N, Hashimoto T, Nishida T (1978) Synthesis of C-peptides and human proinsulin. Diabetes 27:149–160
Okuda J, Okuda G (1969) A rapid polarographic microdetermination of glucose with glucose oxidase. Clin Chim Acta 21:365–367
Starr JI, Rubenstein AH (1974) Metabolism of endogenous proinsulin and insulin in man. J Clin Endocrinol Metab 38:305–308
Campbell J, Rastogi KS (1966) Growth hormone-induced diabetes and high levels of serum insulin in dogs. Diabetes 15:30–43
Pierluissi J (1979) Insulin and glucagon levels in young dogs treated with growth hormone. In: Pierlussi J (ed) Endocrine Pancreas and Diabetes. Excerpta Medica, Int Congr Ser 459: 220–229
Campbell J, Rastogi KS (1969) Actions of growth hormone: Enhancement of insulin utilization with inhibition of insulin effect on blood glucose in dogs. Metabolism 18:930–944
Volk BW, Lazarus SS (1962) Ultramicroscopy of dog islets in growth hormone diabetes. Diabetes 11:426–435
Lacy PE (1975) Endocrine secretory mechanisms. Am J Pathol 79:170–187
Sorenson RL, Steffes MW, Lindall AW (1970) Subcellular localization of proinsulin to insulin conversion in isolated rat islets. Endocrinology 86:88–96
Track NS, Creutzfeldt C, Creutzfeldt W (1976) Human insulinoma tissue: in vitro studies of proinsulin/insulin biosynthesis and release. Horm Metab Res (Suppl) 6:19–25
Pierlussi J, Norwich KH, Green GR, Campbell J (1978) Insulin kinetics in metasomatotrophic diabetes. Metabolism 27:61–70
Gersell DJ, Gingerich RI, Greider MH (1979) Regional distribution and concentration of pancreatic polypeptide in the human and canine pancreas. Diabetes 28:11–15
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Pierluissi, J., Campbell, J. Growth hormone and metasomatotrophic diabetes: effects on insulin and proinsulin of serum and pancreas in dogs. Diabetologia 21, 558–562 (1981). https://doi.org/10.1007/BF00281549
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DOI: https://doi.org/10.1007/BF00281549