Home LiteratureArticle Details
PMID: 993351 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The role of insulin and glucagon in the regulation of basal glucose production in the postabsorptive dog.

The Journal of clinical investigation ·Vol. 58 ·No. 6 ·1976-12-00 ·Pages 1407-18

Cherrington AD, Chiasson JL, Liljenquist JE, Jennings AS, Keller U, Lacy WW

Abstract

The aim of the present experiments was to determine the role of insulin and glucagon in the regulation of basal glucose production in dogs fasted overnight. A deficiency of either or both pancreatic hormones was achieved by infusin somatostatin (1 mug/kg per min), a potent inhibitor of both insulin and glucagon secretion, alone or in combination with intraportal replacement infusions of either pancreatic hormone. Infusion of somatostatin alone caused the arterial levels of insulin and glucagon to drop rapidly by 72+/-6 and 81+/-8%, respectively. Intraportal infusion of insulin and glucagon at rates of 400 muU/kg per min and 1 ng/kg per min, respectively, resulted in the maintenance of the basal levels of each hormone. Glucose production was measured using tracer (primed constant infusion of [3-3H]glucose) and arteriovenous difference techniques. Isolated glucagon deficiency resulted in a 35+/-5% (P less than 0.05) rapid and sustained decrease in glucose production which was abolished upon restoration of the plasma glucagon level. Isolated insulin deficiency resulted in a 52+/-16% (P less than 0.01) increase in the rate of glucose production which was abolished when the insulin level was restored. Somatostatin had no effect on glucose production when the changes in the pancreatic hormone levels which it normally induces were prevented by simultaneous intraportal infusion of both insulin and glucagon. In conclusion, in the anesthetized dog fasted overnight; (a) basal glucagon is responsible for at least one-third of basal glucose production, (b) basal insulin prevents the increased glucose production which would result from the unrestrained action of glucagon, and (c) somatostatin has no acute effects on glucose turnover other than those it induces through perturbation of pancreatic hormone secretion. This study indicates that the opposing actions of the two pancreatic hormones are important in the regulation of basal glucose production in the postabsorptive state.

MeSH Terms
Animals Dogs Fasting Glucagon/antagonists & inhibitors,blood,physiology Glucose/biosynthesis Insulin/blood,physiology Insulin Antagonists Liver/metabolism Somatostatin/pharmacology
Chemicals
Insulin Insulin Antagonists Somatostatin Glucagon Glucose
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Cherrington A D
Chiasson J L
Liljenquist J E
Jennings A S
Keller U
Lacy W W
References (54)
54 references, click to expand
  1. 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):772-7 PMID: 1091266
  2. Estimation of pancreatic IRI output rate and its relations to glucose tolerance in normal anasthetized dogs.
    Diabetologia. 1975 Aug;11(4):291-9 PMID: 1107119
  3. Does somatostatin inhibition of insulin secretion involve two mechanisms of action?
    Proc Natl Acad Sci U S A. 1976 Jan;73(1):248-51 PMID: 1108017
  4. Evidence for a physiologic role of pancreatic glucagon in human glucose homeostasis: studies with somatostatin.
    Metabolism. 1975 Feb;24(2):175-82 PMID: 1113681
  5. Persistent pancreatic glucagon but not insulin response to arginine in pancreatectomized dogs.
    Endocrinology. 1975 Mar;96(3):678-93 PMID: 1116479
  6. High molecular weight glucagon-like immunoreactivity in plasma.
    J Clin Endocrinol Metab. 1975 Feb;40(2):296-302 PMID: 1117980
  7. Comparison of cylic and linear forms of somatostatin in the inhibiton of growth hormone, insulin and glucagon Secretion.
    J Clin Endocrinol Metab. 1975 May;40(5):906-8 PMID: 1127098
  8. Gluconeogenesis from alanine in normal postabsorptive man. Intrahepatic stimulatory effect of glucagon.
    Diabetes. 1975 Jun;24(6):574-84 PMID: 1140513
  9. Heterogeneity of plasma glucagon immunoreactivity in normal, depancreatized, and alloxan-diabetic dogs.
    Metabolism. 1975 Sep;24(9):1021-8 PMID: 1152674
  10. The role of glucagon in the pathogenesis of the endogenous hyperglycemia of diabetes mellitus.
    Metabolism. 1975 Nov;24(11):1287-97 PMID: 1186499
  11. Interrelationship of insulin and glucagon ratios on carbohydrate metabolism in isolated hepatocytes containing high glycogen.
    Biochem Biophys Res Commun. 1975 Dec 1;67(3):1019-27 PMID: 1201057
  12. Glucose turnover values in the dog obtained with various species of labeled glucose.
    Am J Physiol. 1975 Dec;229(6):1662-7 PMID: 1211499
  13. Interaction of somatostatin, glucagon, and insulin on hepatic glucose output in the normal dog.
    Diabetes. 1976 Feb;25(2):116-21 PMID: 1248672
  14. Effect of insulin on utilization and production of circulating glucose.
    Am J Physiol. 1957 Apr;189(1):43-50 PMID: 13424687
  15. THE CROONIAN LECTURE, 1963. GLUCONEOGENESIS.
    Proc R Soc Lond B Biol Sci. 1964 Mar 17;159:545-64 PMID: 14130854
  16. INHIBITION BY INSULIN OF HEPATIC GLUCOSE PRODUCTION IN THE NORMAL DOG.
    Am J Physiol. 1965 Feb;208:301-6 PMID: 14259965
  17. EFFECTS OF INSULIN ON LIVER GLYCOGEN SYNTHESIS AND BREAKDOWN IN THE DOG.
    Am J Physiol. 1965 Feb;208:307-16 PMID: 14259966
  18. ON THE HORMONAL REGULATION OF CARBOHYDRATE METABOLISM; STUDIES WITH C14 GLUCOSE.
    Recent Prog Horm Res. 1963;19:445-88 PMID: 14284029
  19. EFFECT OF INSULIN ON GLUCOSE METABOLISM IN THE DOG AFTER PORTACAVAL TRANSPOSITION.
    Am J Physiol. 1965 Jul;209:221-6 PMID: 14343762
  20. The physiological significance of the secretion of endogenous insulin into the portal circulation. III. Evidence for a direct immediate effect of insulin on the balance of glucose across the liver.
    J Clin Invest. 1960 Mar;39:507-22 PMID: 14419685
  21. Estimation of hepatic blood flow with indocyanine green.
    J Clin Invest. 1962 May;41:1169-79 PMID: 14463639
  22. Inhibition by somatostatin of glucose induced 3':5'-monophsophate (cyclic AMP) accumulation and insulin release in isolated pancreatic islets of the rat.
    FEBS Lett. 1975 Jul 15;55(1):131-3 PMID: 166881
  23. Identification of glucagon in the gastrointestinal tract.
    J Clin Invest. 1975 Jul;56(1):135-45 PMID: 237936
  24. Glucagon control of fasting glucose in man.
    Lancet. 1974 Oct 26;2(7887):974-7 PMID: 4138107
  25. Interactions of glucagon and insulin on the metabolism of perfused livers from fasted rats.
    Eur J Biochem. 1969 May 1;9(1):55-62 PMID: 4306664
  26. Glucagon release induced by pancreatic nerve stimulation in the dog.
    J Clin Invest. 1973 May;52(5):1246-59 PMID: 4349486
  27. Effect of glucagon on net splanchnic cyclic AMP production in normal and diabetic men.
    J Clin Invest. 1974 Jan;53(1):198-204 PMID: 4357612
  28. Stimulation of guanosine 3',5'-cyclic monophosphate accumulation in rat anterior pituitary gland in vitro by synthetic somatostatin.
    Biochem Biophys Res Commun. 1974 Nov 6;61(1):53-7 PMID: 4374210
  29. Effect of glucagon: insulin ratios on hepatic metabolism.
    Diabetes. 1974 Sep;23(9):725-31 PMID: 4413056
  30. Arginine infusion in dogs. Model for the roles of insulin and glucagon in regulating glucose turnover and free fatty acid levels.
    Diabetes. 1974 Oct;23(10):805-15 PMID: 4422477
  31. Increased "glucagon immunoreactivity" in plasma of totally depancreatized dogs.
    Diabetes. 1974 Nov;23(11):905-12 PMID: 4430418
  32. Plasma glucose, insulin, pancreatic, and enteroglucagon levels in normal and depancreatized dogs.
    Proc Soc Exp Biol Med. 1974 Oct;147(1):97-102 PMID: 4438349
  33. Effect of arginine on glucose turnover and plasma free fatty acids in normal dogs.
    Diabetes. 1973 Jul;22(7):537-43 PMID: 4578218
  34. Somatostatin: hypothalamic inhibitor of the endocrine pancreas.
    Science. 1974 Apr 26;184(4135):482-4 PMID: 4594711
  35. Inhibition of pancreatic glucagon release by somatostatin: in vitro.
    Scand J Clin Lab Invest. 1974 Apr;33(2):125-9 PMID: 4604616
  36. Presence of glucagon immunoreactivity in the globulin fraction of human plasma ("big plasma glucagon").
    J Clin Endocrinol Metab. 1974 Dec;39(6):1090-8 PMID: 4610003
  37. Reversal of somatostatin inhibition of insulin secretion by calcium.
    Biochem Biophys Res Commun. 1974 Oct 8;60(3):1015-9 PMID: 4611421
  38. Effect of glucagon on glucose turnover and plasma free fatty acids in depancreatized dogs maintained on matched insulin infusions.
    Can J Physiol Pharmacol. 1972 Oct;50(10):946-54 PMID: 4637182
  39. Measurement and validation of nonsteady turnover rates with applications to the inulin and glucose systems.
    Fed Proc. 1974 Jul;33(7):1855-64 PMID: 4834189
  40. Insulin output via the pancreatic vein and plasma insulin response to glucose in dogs.
    Am J Physiol. 1968 Sep;215(3):620-6 PMID: 4876421
  41. Pancreatic glucagon secretion in normal and diabetic subjects.
    Am J Med Sci. 1969 Jun;257(6):415-9 PMID: 4893149
  42. Secretion of glucagon from the isolated, perfused canine pancreas.
    J Clin Invest. 1971 Oct;50(10):2123-36 PMID: 5116204
  43. Antagonism between the effects of insulin and glucagon on the isolated liver.
    Diabetes. 1969 Nov;18(11):724-32 PMID: 5348515
  44. Effect of D-glucose or D-ribose on the turnover of glucose in pancreatectomized dogs maintained on a matched intraportal infusion of insulin.
    Diabetes. 1969 Dec;18(12):820-7 PMID: 5361445
  45. Hepatic vascular bed.
    Physiol Rev. 1971 Jan;51(1):23-65 PMID: 5543903
  46. Glucoregulatory responses in normal and diabetic dogs recorded by a new tracer method.
    Metabolism. 1971 Apr;20(4):360-72 PMID: 5550303
  47. Role of adenosine 3',5'-monophosphate in the effects of insulin and anti-insulin serum on liver metabolism.
    J Biol Chem. 1968 Mar 10;243(5):1031-8 PMID: 5640968
  48. Matched rates of insulin infusion and secretion and concurrent tracer-determined rates of glucose appearance and disappearance in fasting dogs.
    Can J Physiol Pharmacol. 1968 May;46(3):383-90 PMID: 5698909
  49. Effects of insulin on net carbohydrate alterations in perfused rat liver.
    Am J Physiol. 1967 Jan;212(1):179-83 PMID: 6016000
  50. Glucose-2-t as a tracer for glucose metabolism.
    Biochemistry. 1967 Jan;6(1):1-5 PMID: 6030319
  51. Somatostatin inhibition of insulin and glucagon secretion in rat islet culture: reversal by ionophore A23187.
    Endocrinology. 1976 Jan;98(1):259-62 PMID: 765117
  52. 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):754-62 PMID: 804491
  53. The Banting Memorial Lecture 1975. Diabetes and the alpha cell.
    Diabetes. 1976 Feb;25(2):136-51 PMID: 814024
  54. 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):753-61 PMID: 946565
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
Published
1976-12-00
Pages
1407-18
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC333312
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]