Abstract
Cyclic somatostatin was administered intravenously (10 mug/min for 60 min) to 10 healthy overnight fasted (postabsorptive) subjects and to 5 healthy 60-h fasted subjects. In both groups, arterial insulin and glucagon fell 50% and splanchnic release of these hormones was inhibited. In the overnight fasted subjects splanchnic glucose output fell 70%, splanchnic uptake of lactate and pyruvate was unchanged, alanine uptake fell by 25%, and glycerol uptake rose more than twofold in parallel with an increase in arterial glycerol. In the 60-h fasted group splanchnic glucose output was less than 40% of that observed in the overnight fasted subjects. Somatostatin led to a further decrease (--70%) in glucose production. Splanchnic uptake of lactate and pyruvate fell by 30-40%, amino acid uptake was unchanged, while uptake of glycerol rose fivefold. Total uptake of glucose precursors thus exceeded the simultaneous glucose output by more than 200%. Splanchnic uptake of FFA rose fourfold during somatostatin while output of beta-hydroxybutyrate increased by 75%. Estimated hepatic blood flow fell 25-35% and returned to base line as soon as the somatostatin infusion ended. It is concluded that (a) somatostatin-induced hypoglucagonemia results in inhibition of splanchnic glucose output in glycogen-depleted, 60-h fasted subjects as well as in postabsorptive subjects, indicating an effect of glucagon on hepatic gluconeogenesis as well as glycogenolysis; (b) the glucagonsensitive step(s) in gluconeogenesis affected by somatostatin involves primarily intra-hepatic disposal rather than net hepatic uptake of glucose precursors; (c) splanchnic uptake of fatty acids and ketone output are increased in the face of combined insulin and glucagon deficiency; and (d) diminished splanchnic blood flow may contribute to some of the effects of somatostatin on splanchnic metabolism.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aguilar-Parada E., Eisentraut A. M., Unger R. H. Pancreatic glucagon secretion in normal and diabetic subjects. Am J Med Sci. 1969 Jun;257(6):415–419. doi: 10.1097/00000441-196906000-00008. [DOI] [PubMed] [Google Scholar]
- Alberti K. G., Christensen N. J., Christensen S. E., Hansen A. P., Iversen J., Lundbaek K., Seyer-Hansen K., Orskov H. Inhibition of insulin secretion by somatostatin. Lancet. 1973 Dec 8;2(7841):1299–1301. doi: 10.1016/s0140-6736(73)92873-0. [DOI] [PubMed] [Google Scholar]
- Altszuler N., Gottlieb B., Hampshire J. Interaction of somatostatin, glucagon, and insulin on hepatic glucose output in the normal dog. Diabetes. 1976 Feb;25(2):116–121. doi: 10.2337/diab.25.2.116. [DOI] [PubMed] [Google Scholar]
- Bradley S. E., Ingelfinger F. J., Bradley G. P., Curry J. J. THE ESTIMATION OF HEPATIC BLOOD FLOW IN MAN. J Clin Invest. 1945 Nov;24(6):890–897. doi: 10.1172/JCI101676. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brazeau P., Vale W., Burgus R., Ling N., Butcher M., Rivier J., Guillemin R. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science. 1973 Jan 5;179(4068):77–79. doi: 10.1126/science.179.4068.77. [DOI] [PubMed] [Google Scholar]
- Chiasson J. L., Liljenquist J. E., Sinclair-Smith B. C., Lacy W. W. Gluconeogenesis from alanine in normal postabsorptive man. Intrahepatic stimulatory effect of glucagon. Diabetes. 1975 Jun;24(6):574–584. doi: 10.2337/diab.24.6.574. [DOI] [PubMed] [Google Scholar]
- Chideckel E. W., Palmer J., Koerker D. J., Ensinck J., Davidson M. B., Goodner C. J. Somatostatin blockade of acute and chronic stimuli of the endocrine pancreas and the consequences of this blockade on glucose homeostasis. J Clin Invest. 1975 Apr;55(4):754–762. doi: 10.1172/JCI107986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeVane G. W., Siler T. M., Yen S. S. Acute suppression of insulin and glucose levels by synthetic somatostatin in normal human subjects. J Clin Endocrinol Metab. 1974 May;38(5):913–915. doi: 10.1210/jcem-38-5-913. [DOI] [PubMed] [Google Scholar]
- Efendic S., Luft R., Grill V. Effect of somatostatin on glucose induced insulin release in isolated perfused rat pancreas and isolated rat pancreatic islets. FEBS Lett. 1974 Jun 1;42(2):169–172. doi: 10.1016/0014-5793(74)80778-7. [DOI] [PubMed] [Google Scholar]
- Efendić S., Claro A., Laft R. Studies on the mechanism of somatostatin action on insulin release. III. Effect of somatostatin on arginine induced release of insulin and glucagon in man and perfused rat pancreas. Acta Endocrinol (Copenh) 1976 Apr;81(4):753–761. [PubMed] [Google Scholar]
- Efendić S., Luft R., Claro A. Studies on the mechanism of somatostatin action on insulin release in man. II. Comparison of the effects of somatostatin on insulin release induced by glucose, glucagon and tolbutamide. Acta Endocrinol (Copenh) 1976 Apr;81(4):743–752. doi: 10.1530/acta.0.0810743. [DOI] [PubMed] [Google Scholar]
- FAWCETT J. K., SCOTT J. E. A rapid and precise method for the determination of urea. J Clin Pathol. 1960 Mar;13:156–159. doi: 10.1136/jcp.13.2.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garber A. J., Menzel P. H., Boden G., Owen O. E. Hepatic ketogenesis and gluconeogenesis in humans. J Clin Invest. 1974 Oct;54(4):981–989. doi: 10.1172/JCI107839. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerich J. E., Lorenzi M., Bier D. M., Tsalikian E., Schneider V., Karam J. H., Forsham P. H. Effects of physiologic levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. Studies involving administration of exogenous hormone during suppression of endogenous hormone secretion with somatostatin. J Clin Invest. 1976 Apr;57(4):875–884. doi: 10.1172/JCI108364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerich J. E., Lorenzi M., Hane S., Gustafson G., Guillemin R., Forsham P. H. Evidence for a physiologic role of pancreatic glucagon in human glucose homeostasis: studies with somatostatin. Metabolism. 1975 Feb;24(2):175–182. doi: 10.1016/0026-0495(75)90018-9. [DOI] [PubMed] [Google Scholar]
- Gerich J. E., Lorenzi M., Schneider V., Forsham P. H. Effect of somatostatin on plasma glucose and insulin responses to glucagon and tolbutamide in man. J Clin Endocrinol Metab. 1974 Dec;39(6):1057–1060. doi: 10.1210/jcem-39-6-1057. [DOI] [PubMed] [Google Scholar]
- HUGGETT A. S., NIXON D. A. Use of glucose oxidase, peroxidase, and O-dianisidine in determination of blood and urinary glucose. Lancet. 1957 Aug 24;273(6991):368–370. doi: 10.1016/s0140-6736(57)92595-3. [DOI] [PubMed] [Google Scholar]
- Hagenfeldt L. A gas chromatographic method for the determination of individual free fatty acids in plasma. Clin Chim Acta. 1966 Feb;13(2):266–268. doi: 10.1016/0009-8981(66)90304-4. [DOI] [PubMed] [Google Scholar]
- Hall R., Besser G. M., Schally A. V., Coy D. H., Evered D., Goldie D. J., Kastin A. J., McNeilly A. S., Mortimer C. H., Phenekos C. Action of growth-hormone-release inhibitory hormone in healthy men and in acromegaly. Lancet. 1973 Sep 15;2(7829):581–584. doi: 10.1016/s0140-6736(73)92413-6. [DOI] [PubMed] [Google Scholar]
- Koerker D. J., Ruch W., Chideckel E., Palmer J., Goodner C. J., Ensinck J., Gale C. C. Somatostatin: hypothalamic inhibitor of the endocrine pancreas. Science. 1974 Apr 26;184(4135):482–484. doi: 10.1126/science.184.4135.482. [DOI] [PubMed] [Google Scholar]
- Mattes P., Raptis S., Heil T., Rasche H., Scheck R. Extended somatostatin treatment of a patient with bleeding ulcer. Horm Metab Res. 1975 Nov;7(6):508–511. doi: 10.1055/s-0028-1093714. [DOI] [PubMed] [Google Scholar]
- Nilsson L. H., Fürst P., Hultman E. Carbohydrate metabolism of the liver in normal man under varying dietary conditions. Scand J Clin Lab Invest. 1973 Dec;32(4):331–337. doi: 10.3109/00365517309084356. [DOI] [PubMed] [Google Scholar]
- Oliver J. R., Wagle S. R. Studies on the inhibition of insulin release, glycogenolysis and gluconeogenesis by somatostatin in the rat islets of langerhans and isolated hepatocytes. Biochem Biophys Res Commun. 1975 Feb 3;62(3):772–777. doi: 10.1016/0006-291x(75)90466-0. [DOI] [PubMed] [Google Scholar]
- ROWELL L. B., BLACKMON J. R., BRUCE R. A. INDOCYANINE GREEN CLEARANCE AND ESTIMATED HEPATIC BLOOD FLOW DURING MILD TO MAXIMAL EXERCISE IN UPRIGHT MAN. J Clin Invest. 1964 Aug;43:1677–1690. doi: 10.1172/JCI105043. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosselin G., Assan R., Yalow R. S., Berson S. A. Separation of antibody-bound and unbound peptide hormones labelled with iodine-131 by talcum powder and precipitated silica. Nature. 1966 Oct 22;212(5060):355–357. doi: 10.1038/212355a0. [DOI] [PubMed] [Google Scholar]
- Sakurai H., Dobbs R., Unger R. H. Somatostatin-induced changes in insulin and glucagon secretion in normal and diabetic dogs. J Clin Invest. 1974 Dec;54(6):1395–1402. doi: 10.1172/JCI107886. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sherwin R., Wahren J., Felig P. Evanescent effects of hypo- and hyperglucagonemia on blood glucose homeostasis. Metabolism. 1976 Nov;25(11 Suppl 1):1381–1383. doi: 10.1016/s0026-0495(76)80146-1. [DOI] [PubMed] [Google Scholar]
- WILLIAMSON D. H., MELLANBY J., KREBS H. A. Enzymic determination of D(-)-beta-hydroxybutyric acid and acetoacetic acid in blood. Biochem J. 1962 Jan;82:90–96. doi: 10.1042/bj0820090. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wahren J., Felig P., Ahlborg G., Jorfeldt L. Glucose metabolism during leg exercise in man. J Clin Invest. 1971 Dec;50(12):2715–2725. doi: 10.1172/JCI106772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wahren J. Quantitative aspects of blood flow and oxygen uptake in the human forearm during rhythmic exercise. Acta Physiol Scand Suppl. 1966;269:1–93. [PubMed] [Google Scholar]