Summary
Under normal conditions, glucose acutely influences pancreatic islet B, A and D cell secretion. In addition, prior exposure to glucose modulates the secretory responsiveness of these cells (priming effect). We have tested whether alloxan diabetes influences priming effects of glucose on A and D cell secretion. Rat pancreases were perfused 72 h after alloxan treatment. A 20 min infusion of 27.7 mmol/l of glucose failed to induce priming effects, i. e. it did not inhibit the glucagon nor amplify the somatostatin response to a subsequent (15 min later) infusion of 8 mmol/l of arginine. Insulin treatment in vivo for 48 h restored a priming effect of glucose on glucagon secretion in the perfused pancreas, i. e. exposure to 27.7 mmol/l of glucose now inhibited subsequent arginine-induced glucagon secretion by 48% relative to a stimulation period with arginine preceding the glucose pulse (from 5.0±0.7 to 2.6±0.5 ng/min, p<0.01). Conversely, insulin treatment in vivo did not restore a priming effect of glucose on somatostatin secretion. Other effects noted were failure of 27.7 mmol/l glucose to stimulate, during its presence, the release of somatostatin from pancreases of the diabetic rats whether untreated or insulin-treated. Furthermore, insulin treatment abolished the arginine-induced somatostatin secretion observed in pancreases from untreated rats. It is concluded that short-term alloxan diabetes leads to loss of a priming effect of glucose on glucagon secretion and that this abnormality is secondary to direct or indirect effects of insulinopenia. Concomittant abnormalities of glucose regulation of somatostatin secretion may, in part, be secondary to a cytotoxic effect of alloxan on the D cell.
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References
Gerich JE, Charles MA, Grodsky GM (1976) Regulation of pancreatic insulin and glucagon secretion. In: Knobil E, Sonnenschein RR, Edelman IS (eds) Annual Review of Physiology, vol 38. Annual Reviews, Palo Alto, pp 353–388
Hermansen K (1980) Secretion of somatostatin from the normal and diabetic pancreas. Studies in vitro. Diabetologia 19: 492–505
Grodsky GM, Curry D, Landahl H, Bennett LL (1969) Further studies on the dynamic aspects of insulin release in vitro with evidence for a two-compartmental storage system. Acta Diabetol Lat 7 (Suppl 1): 554–579
Cerasi E (1975) Potentiation of insulin release by glucose in man. I Quantitative analysis of the enhancement of glucose-induced insulin secretion by pretreatment with glucose in normal subjects. Acta Endocrinol 79: 483–501
Grill V, Adamson U, Cerasi E (1978) Immediate and time-dependent effects of glucose on insulin release from rat pancreatic tissue. J Clin Invest 61:1034–1043
Grill V, Rundfeldt M (1979) Effects of priming with glucose on insulin secretion from rat pancreatic islets. Increased responsiveness to other secretagogues. Endocrinology 105: 980–987
Kanatsuka A, Makino H, Matsushima Y, Osegawa M, Kasanuki J, Miyahira M, Yamamoto M, Kumagai A (1981) Effect of glucose on somatostatin secretion from isolated pancreatic islets of normal and streptozotocin-diabetic rats. Endocrinology 109: 652–657
Grill V, Rundfeldt M, Efendić S (1981) Previous exposure to glucose enhances somatostatin secretion from the isolated perfused rat pancreas. Diabetologia 20: 495–500
Grill V, Adamson U, Rundfeldt M, Andersson S, Cerasi E (1979) The glucose memory of pancreatic B and A2 cells. Evidence for common time dependent actions of glucose on insulin and glucagon secretion. J Clin Invest 64: 700–707
Adamson U, Grill V, Efendić S (1981) Previous exposure to glucose enhances insulin and suppresses glucagon responses to arginine in man. Acta Diabetol Lat 18:173–179
Unger RH (1978) Role of glucagon in the pathogenesis of diabetes: the status of the controversy. Metabolism 27:1691–1709
Loubatières A, Mariani MM, Ribes G, de Malbosc H (1969) Etude expérimentale d'un nouveau sulfamide hypoglycémiant particuliérement actif, le HB 419 ou glibenclamide. I. Action bêtacytotrope et insulinosécrétrice. Diabetologia 5:1–10
Hugget AS, Nixon DA (1957) Use of glucose oxidase peroxidase and o-dianisidine in determination of blood and urinary glucose. Lancet 2: 368–370
Herbert V, Lau KS, Gottlieb CW, Bleicher SJ (1965) Coated charcoal immunoassay of insulin. J Clin Endocrinol 25:1375–1384
Faloona GR, Unger RH (1974) Methods of hormone radioimmunassay. In: Jaffe BM, Behrman HR (eds) Radioimmunoassay technique. Academic Press, London, New York, pp 324–326
Efendić S, Nylén A, Roovete A, Uvnäs-Wallensten K (1978) Effects of glucose and arginine on the release of immunoreactive somatostatin from the isolated perfused rat pancreas. FEBS Lett 92:33–35
Efendić S, Enzmann F, Nylén A, Uvnäs-Wallensten K, Luft R (1979) Effect of glucose/sulfonylurea interaction on release of insulin, glucagon and somatostatin from isolated perfused rat pancreas. Proc Natl Acad Sci USA 76: 5901–5904
Rerup CC (1970) Drugs producing diabetes through damage of the insulin secreting cells. In: de V. Cotten M. (ed) Pharmacological Reviews. Vol 22. Williams & Wilkins, Baltimore, pp 485–518
Pagliara AS, Stillings SN, Zawalich WS, Williams AD, Matschinsky FM (1977) Glucose and 3-0-methylglucose protection against alloxan poisoning of pancreatic alpha and beta cells. Diabetes 26: 973–979
Goto Y, Berelowitz M, Frohman LA (1976) Acute effects of alloxan and streptozotocin-induced insulin deficiency on somatostatin and glucagon secretion by the perfused isolated rat pancreaticoduodenal preparation. Diabetologia 20: 66–71
Matschinsky FM, Pagliara AS, Hover BA, Pace CS, Ferendelli JA, Williams A (1976) Hormone secretion and glucose metabolism in islets of Langerhans of the isolated perfused pancreas from normal and streptozotocin diabetic rats. J Biol Chem 251: 6053–6061
Buchanan KD, Mawhinney WAA (1973) Insulin control of glucagon release from insulin deficient rat islets. Diabetes 22: 801–803
Pagliara AS, Stillings SN, Haymond MW, Hover BA, Matschinsky FM (1975) Insulin and glucose as modulators of the amino acid-induced glucagon release in the isolated pancreas of alloxan and streptozotocin diabetic rats. J Clin Invest 55: 244–255
Weir GC, Knowlton SD, Atkins RF, McKennan KX, Martin DB (1976) Glucagon secretion from the perfused pancreas of streptozotocin-treated rats. Diabetes 25: 275–282
Schusdziarra V, Rouiller D, Harris V, Conlon JM, Unger RH (1978) The response of plasma somatostatin-like immunoreactivity in normal and alloxan diabetic dogs. Endocrinology 103: 2264–2273
Hermansen K, Ørskov H, Christensen SE (1979) Streptozotocin diabetes: A glucoreceptor dysfunction affecting D cells as well as B and A cells. Diabetologia 17: 385–389
Trimble ER, Gerber PPG, Renold AE (1981) Abnormalities of pancreatic somatostatin secretion corrected by in vivo insulin treatment of streptozotocin-diabetic rats. Diabetes 30: 865–867
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Grill, V., Efendić, S. Loss of a priming effect of glucose on A and D cell secretion in perfused pancreases from alloxan-diabetic rats: Role of insulin and alloxan. Diabetologia 24, 47–51 (1983). https://doi.org/10.1007/BF00275947
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DOI: https://doi.org/10.1007/BF00275947