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Horm Metab Res 2005; 37(1): 40-44
DOI: 10.1055/s-2005-861035
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Acute Insulin Responses to Intravenous Glucose and GLP-1 are Independent of Preceding High-frequency Insulin Pulse-defects Induced by Glucose Entrainment in Healthy Humans

C.  B.  Juhl1, 2 , J.  Sturis3 , M.  Hollingdal1 , O.  Schmitz1, 2
  • 1Medical Department M (Endocrinology and Diabetes), University Hospital of Århus, Denmark
  • 2Institute of Clinical Pharmacology, University of Århus, Denmark
  • 3Pharmacology, Novo Nordisk A/S, Bagsværd, Denmark
Further Information

Publication History

Received 23 March 2004

Accepted after Revision 15 September 2004

Publication Date:
09 February 2005 (online)

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Abstract

The objective of this study was to test the hypothesis that high-frequency oscillations in insulin release is a part of the mechanistic basis of a prompt and adequate insulin response to iv-glucose and GLP-1 exposure. In ten healthy subjects, five different insulin release patterns were induced for 360 min using computer-based glucose infusion (glucose delivered in a constant, a regular pulsatile, an irregular pulse frequency, an irregular pulse amplitude or a regular but very fast-pulsatile manner) in healthy subjects. The amount of glucose infused was identical in all five protocols (24 mg/kg/h). After 360 min, insulin secretion was assessed by means of a first-phase insulin secretion test (25 g glucose) and injection of GLP-1 (9 μg). By frequent blood sampling and analysis of insulin concentration, glucose-induced entrainment was evident in all protocols except in the constant infusion and the very fast-pulse protocol. The first-phase insulin release to glucose and GLP-1-induced insulin release were, however, comparable in the protocols. We therefore conclude from this short-term experimental setting in healthy subjects that beta-cell response to either iv-glucose or GLP-1 is independent of the preceding regularity of oscillations in insulin release.

Key words

Insulin secretion - Entrainment - Pulsatility - Human

References

  • 1 Goodner C J, Walike B C, Koerker D J, Ensinck J W, Brown A C, Chideckel E W, Palmer J, Kalnasy L. Insulin, glucagon and glucose exhibit synchronous, sustained oscillations in fasting monkeys.  Science. 1977;  195 177-179
    PubMedSearch in Google Scholar
  • 2 Lang D A, Matthews D R, Peto J, Turner R C. Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings.  N Engl J Med. 1979;  301 1023-1027
    PubMedSearch in Google Scholar
  • 3 Juhl C B, Porksen N, Sturis J, Prange A, Veldhuis J D, Pincus S M, Fineman M S, Schmitz O. High frequency oscillations in circulating amylin concentrations in healthy humans.  Am J Physiol. 2000;  278 E484-490
    PubMedSearch in Google Scholar
  • 4 Lang D A, Matthews D R, Burnett M, Turner R C. Brief, irregular oscillations of basal plasma insulin and glucose concentrations in diabetic man.  Diabetes. 1981;  30 435-439
    PubMedSearch in Google Scholar
  • 5 Polonsky K S, Given B D, Hirsch L J, Tillil H, Shapiro E T, Beebe C, Frank B H, Galloway J A, van Cauter E. Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus.  N Engl J Med. 1988;  318 1231-1239
    CrossrefPubMedSearch in Google Scholar
  • 6 O’Rahilly S, Turner R C, Matthews D R. Impaired pulsatile secretion of insulin in relatives of patients with non-insulin-dependent diabetes.  N Engl J Med. 1988;  318 1225-1230
    PubMedSearch in Google Scholar
  • 7 Schmitz O, Porksen N, Nyholm B, Skjaerbaek C, Butler P C, Veldhuis J D, Pincus S M. Disorderly and nonstationary insulin secretion in relatives of patients with NIDDM.  Am J Physiol. 1997;  272 E218-26
    PubMedSearch in Google Scholar
  • 8 Bratusch M arrain, Komjati M, Waldhausl W K. Efficacy of pulsatile vs. continuous insulin administration on hepatic glucose production and glucose utilization in type I diabetic humans.  Diabetes. 1986;  35 922-926
    PubMedSearch in Google Scholar
  • 9 Paolisso G, Scheen A J, Albert A, Lefebvre P J. Effects of pulsatile delivery of insulin and glucagon in humans.  Am J Physiol. 1989;  257 E686-E696
    PubMedSearch in Google Scholar
  • 10 Matthews D R, Naylor B A, Jones R G, Ward G M, Turner R C. Pulsatile insulin has greater hypoglycemic effect than continuous delivery.  Diabetes. 1983;  32 617-621
    PubMedSearch in Google Scholar
  • 11 Courtney C H, Atkinson A B, Ennis C N, Sheridan B, Bell P M. Comparison of the priming effects of pulsatile and continuous insulin delivery on insulin action in man.  Metabolism. 2003;  52 1050-1055
    CrossrefPubMedSearch in Google Scholar
  • 12 Chou H F, Berman N, Ipp E. Evidence for pancreatic pacemaker for insulin oscillations in low-frequency range.  Am J Physiol. 1994;  266 R1786-R1791
    PubMedSearch in Google Scholar
  • 13 Porksen N K, Juhl C B, Grøfte T, Hollingdal M, Sturis J, Veldhuis J D, Schmitz O. Induction of rapid insulin secretion in healthy humans by periodic glucose insfusion.  Diabetes. 1998;  suppl (1), abstract nr 992
    PubMedSearch in Google Scholar
  • 14 Vilsboll T, Toft-Nielsen M B, Krarup T, Madsbad S, Dinesen B, Holst J J. Evaluation of beta-cell secretory capacity using glucagon-like peptide 1.  Diabetes Care. 2000;  23(6) 807-812
    PubMedSearch in Google Scholar
  • 15 Andersen L, Dinesen B, Jorgensen P N, Poulsen F, Roder M E. Enzyme immunoassay for intact human insulin in serum or plasma.  Clin Chem. 1993;  39 578-582
    PubMedSearch in Google Scholar
  • 16 Polonsky K S, Licinio-Paixao J, Given B D, Pugh W, Rue P, Galloway J, Karrison T, Frank B. Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients.  J Clin Invest. 1986;  77(1) 98-105
    PubMedSearch in Google Scholar
  • 17 Van Cauter E, Mestrez F, Sturis J, Polonsky K S. Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance.  Diabetes. 1992;  41 368-377
    CrossrefPubMedSearch in Google Scholar
  • 18 Eaton R P, Allen R C, Schade D S, Erickson K M, Standefer J. Prehepatic insulin production in man: kinetic analysis using peripheral connecting peptide behavior.  J Clin Endocrinol Metab. 1980;  51 520-528
    CrossrefPubMedSearch in Google Scholar
  • 19 Chatfield C. The analysis of time series. An introduction. 5th ed. London; Chapman and Hall 1996
    Search in Google Scholar
  • 20 Smith C P, Tarn A C, Thomas J M, Overkamp D, Corakci A, Savage M O, Gale E A. Between and within subject variation of the first phase insulin response to intravenous glucose.  Diabetologia. 1988;  31 123-125
    CrossrefPubMedSearch in Google Scholar
  • 21 Daniel S, Noda M, Straub S G, Sharp G W. Identification of the docked granule pool responsible for the first phase of glucose-stimulated insulin secretion.  Diabetes. 1999;  48 1686-1690
    PubMedSearch in Google Scholar
  • 22 Bratanova-Tochkova T K, Cheng H, Daniel S, Gunawardana S, Liu Y J, Mulvaney-Musa J, Schermerhorn T, Straub S G, Yajima H, Sharp G W. Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion.  Diabetes. 2002;  51 Suppl 1 S83-S90
    PubMedSearch in Google Scholar
  • 23 Fichaux F, Bonnafous R. Responsiveness and memory of the pancreatic B-cells to the insulin secretagogues D-glucose and L-arginine in prediabetic and diabetic rabbits.  Pancreas. 1992;  7 585-594
    PubMedSearch in Google Scholar
  • 24 Porksen N, Juhl C B, Hollingdal M, Pincus S M, Sturis J, Veldhuis J D, Schmitz O. Concordant induction of rapid in vivo pulsatile insulin secretion by recurrent punctuated glucose infusions.  Am J Physiol. 2000;  278 E162-170
    PubMedSearch in Google Scholar

C. B. Juhl

Medical Department M (Endocrinology and Diabetes), University Hospital of Århus ·

Noerrebrogade 44 · 8000 Århus C · Denmark

Email: claus.juhl@dadlnet.dk