Summary
We studied insulin receptor binding and carbohydrate metabolism in 10 patients with severe hyperprolactinaemia and compared the findings with those obtained in 20 healthy control subjects. Insulin binding to monocytes and erythrocytes was significantly decreased in the patients with an excess of prolactin. Scatchard analysis of binding data indicated that a decrease in the number of receptors rather than in receptor affinity seems to be the prevailing cause of lowered binding in hyperprolactinaemic patients. Furthermore, patients with severe hyperprolactinaemia demonstrated significantly elevated blood glucose levels following oral or intravenous glucose load despite having significantly increased insulin levels after glucose administration. The infusion of insulin induced a delayed hypoglycaemic effect and a decreased inhibition of endogenous insulin secretion, as indicated by the suppression of C-peptide in the hyperprolactinaemic patients. The present data indicate that severe hyperprolactinaemia is associated with an insulin-resistant state, which seems to be caused, at least in part, by a down-regulation of insulin receptors.
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Houssay BA, Penhos JC (1956) Diabetogenic action of pituitary hormones on adrenalectomized hypophysectomized dogs. Endocrinology 59: 637–641
Rathgeb IB, Winkler B, Steele R, Altszuler N (1971) Effect of ovine prolactin administration on glucose metabolism and plasma insulin levels in the dog. Endocrinology 88: 718–722
Beck JC, Gonda A, Hamid MA, Morgen RO, Rubinstein D, McGarry EE (1964) Some metabolic changes induced by primate growth hormone and purified ovine prolactin. Metabolism 13: 1108–1134
Landgraf R, Landgraf-Leurs MMC, Weissmann A, Hörl R, von Werder K, Scriba PC (1977) Prolactin: a diabetogenic hormone. Diabetologia 13: 99–104
Gustafson AB, Banasiak MF, Kalkhoff RK, Hagen TC, Hak-Joong K (1980) Correlation of hyperprolactinaemia with altered plasma insulin and glucagon: similarity to effects of late human pregnancy. J Clin Endocrinol Metab 51: 241–246
Johnston DG, Alberti KGMM, Nattrass M, Burrin JM, Blesa-Malpica G, Hall K, Hall R (1980) Hyperinsulinaemia in hyperprolactinaemic women. Clin Endocrinol 13: 361–368
Katz EJ, Donald RA, Beaven DW, Espiner EA (1981) Lack of effect of hyperprolactinaemia on glucose disposal and insulin secretion in patients with prolactinomas. Horm Metab Res 13: 667–669
Hagen C, Pedersen PB, Jensen SB, Faber OK, Jensen T (1979) The effect of supiride induced hyperprolactinaemia on glucose tolerance and insulin secretion in normal subjects. Clin Endocrinol 10: 55–60
Harter M, Krebs N, Balarac JM, Kozlowski RM, Chichmaninan S, Strulo S, Carnivet B (1978) Interrelations between prolactin and carbohydrates. In: Robyn C, Harter M (eds) Progress in prolactin, physiology and pathology. Elsevier/North-Holland, Biomedical Press, pp 331–349
Adler RA, Sokol HW (1982) Glucose tolerance in rats with elevated circulating prolactin levels. Horm Metab Res 14: 307–309
Renauld A, Sverdlik RC, Andrade LL (1973) The effect of chronic prolactin administration upon the blood sugar, insulin and free fatty acid response to a glucose load in the dog. Acta Diabetol Lat 10: 1286–1299
WHO Expert Committee on Diabetes mellitus (1980) WHO Tech Rep 646
Boyum A (1968) Separation of leukocytes from blood and bone marrow. Scand J Lab Clin Invest 22 (Suppl 97): 77–89
Beck Nielsen H, Pedersen O, Kragballe K, Sörensen NS (1977) The monocytes as a model for the study of insulin receptors in men. Diabetologia 13: 563–569
Prager R, Schernthaner G (1983) Insulin receptor binding to monocytes, insulin secretion and glucose tolerance following metformin treatment, results of a double blind cross-over study in type II diabetics. Diabetes 32: 1083–1086
Yam LT, Li CY, Crosby WN (1971) Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol 55: 283–286
Pedersen O, Beck Nielsen H, Heding L (1980) Increased insulin receptors after exercise in patients with insulin dependent diabetes mellitus. New Engl J Med 302: 886–892
Scatchard G (1949) The attraction proteins for small molecules and ions. Ann NY Acad Sci 51: 660–672
DeMeyts P, Roth J (1975) Cooperativity in ligand binding: A new graphic analysis. Biochem Biophys Res Commun 66: 1118–1126
Carter JN, Tyson JE, Warne GL, McNeilly AS, Faiman C, Friesen HG (1977) Adrenocortical function in hyperprolactinemic women. J Clin Endocrinol Metab 45: 973–980
Lenzen S, Bailey CJ (1984) Thyroid hormones, gonadal and adrenocortical steroids and the function of the islets of Langerhans. Endocr Rev 5: 411–434
Shoupe D, Lobo RA (1984) The influence of androgens on insulin resistance. Fertil Steril 41: 385–388
Yki-Järvinen H (1984) Insulin sensitivity during the menstrual cycle. J Clin Endocrinol Metab 59: 350–353
Pedersen O, Hjollund E, Lindskov HO (1982) Insulin binding and action on fat cells from young healthy females and males. Am J Physiol 243: E158
Luger A, Graf H, Prager R, Schernthaner G (1984) Decreased peripheral insulin sensitivity in hyperprolactinemic patients. Acta Endocrinol (Copenh) 105 (Suppl 364): 44
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Schernthaner, G., Prager, R., Punzengruber, C. et al. Severe hyperprolactinaemia is associated with decreased insulin binding in vitro and insulin resistance in vivo. Diabetologia 28, 138–142 (1985). https://doi.org/10.1007/BF00273860
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DOI: https://doi.org/10.1007/BF00273860