PDF herunterladen
Horm Metab Res 2006; 38(2): 94-97
DOI: 10.1055/s-2006-925125
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Meal-dependent Regulation of Circulating Glycated Insulin in Type 2 Diabetic Subjects

A.  M.  McKillop1 , J.  R.  Lindsay2 , S.  Au2 , K.  I.  Mahood1 , F.  P.  M.  O’Harte1 , P.  R.  Flatt1 , P.  M.  Bell2
  • 1School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland
  • 2Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, Northern Ireland
Weitere Informationen

Publikationsverlauf

Received 6 June 2005

Accepted after revision 17 August 2005

Publikationsdatum:
08. März 2006 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

There is mounting evidence that elevated circulating concentrations of glycated insulin play a role in insulin resistance in type 2 diabetes. This study evaluated the secretion of glycated insulin in response to enteral stimulation in type 2 diabetic subjects. Following a mixed meal (450 kcal; 44 % carbohydrate; 40 % fat; 16 % protein), glycated insulin rose 10-fold to peak (60 min) at 104.5 ± 25.0 pmol/l (p < 0.001), representing 22 % total circulating insulin. The response paralleled early rises in insulin and C-peptide, which peaked at 90 min and were more protracted. Maximum glucose concentrations were observed at 50 min. These data indicate that type 2 diabetic subjects exhibit a rapid meal-induced release of glycated insulin from readily releasable pancreatic beta-cell stores, which might contribute to impaired glucose homeostasis following enteral nutrition.

Key words

Glycated insulin - meal - type 2 diabetes

References

  • 1 Unger R H, Grundy S. Hyperglycaemia as an inducer as well as a consequence of impaired islet cell function and insulin resistance: Implications of the management of diabetes.  Diabetologia. 1985;  28 119-121
    PubMedSuche in Google Scholar
  • 2 Leahy J L. B-cell dysfunction with chronic hyperglycaemia: overworked beta cell hypothesis.  Diabetes Revs. 1996;  4 298-319
    PubMedSuche in Google Scholar
  • 3 Sato E, Mori F, Igarashi S, Abiko T, Takeda M, Ishika S, Yoshida A. Corneal advanced glycation end products increase in patients with proliferative diabetic retinopathy.  Diabetes Care. 2001;  24 479-482
    PubMedSuche in Google Scholar
  • 4 Schinzel R, Munch G, Heidland A, Sebekova K. Advanced glycation end products in end-stage renal disease and their removal.  Nephron. 2001;  87 295-303
    CrossrefPubMedSuche in Google Scholar
  • 5 Aso Y, Inukai T, Tayama K, Takemura Y. Serum concentrations of advanced glycation endproducts are associated with the development of atherosclerosis as well as diabetic microangiopathy in patients with type 2 diabetes.  Acta Diabetol. 2000;  37 87-92
    CrossrefPubMedSuche in Google Scholar
  • 6 Brownlee M. Glycation and diabetic complications.  Diabetes. 1993;  43 836-841
    PubMedSuche in Google Scholar
  • 7 Lyons T J, Jenkins A J. Glycation, oxidation, and lipoxidation in the development of the complications of diabetes: a carbonyl stress hypothesis.  Diabetes Reviews. 1997;  5 365-391
    PubMedSuche in Google Scholar
  • 8 Eizirik E L, Korbutt G S, Hellerstrom C. Prolonged exposure of human pancreatic islets to high glucose concentrations in vitro impairs the β-cell function.  J Clin Invest. 1992;  90 1263-1268
    PubMedSuche in Google Scholar
  • 9 Svensson C, Sandler S, Hellerstrom C. Lack of long term β-cell glucotoxicity in vitro in pancreatic islets isolated from two mouse strains (C57BL/6J; C57BL/KsJ) with different sensitivities of the β-cells to hyperglycaemia in vivo. .  J Endocrinol. 1993;  136 289-296
    PubMedSuche in Google Scholar
  • 10 McKillop A M, Abdel-Wahab Y HA, Mooney M H, O'Harte F PM, Flatt P R. Secretion of glycated insulin from pancreatic B-cells in diabetes represents a novel aspect of B-cell dysfunction and glucose toxicity.  Diabetes and Metabolism. 2002;  28 3S61-3S69
    PubMedSuche in Google Scholar
  • 11 Oda A, Bannai C, Yamaoka T, Katori T, Matsushima T, Yamashita K. Inactivation of Cu, Zn-superoxide dismutase by in vitro glycosylation and in erythrocytes of diabetic patients.  Horm Metab Res. 1994;  26 1-4
    PubMedSuche in Google Scholar
  • 12 O"Harte F PM, Abdel-Wahab Y HA, Conlon J M, Flatt P R. Amino terminal glycation of gastric inhibitory polypeptide enhances its insulinotropic action on clonal pancreatic B-cells.  Biochim Biophys Acta. 1998;  1425 319-327
    PubMedSuche in Google Scholar
  • 13 O"Harte F PM, Mooney M H, Kelly C M, Flatt P R. Glycated cholecystokinin-8 has an enhanced satiating activity and is protected against enzymatic degradation.  Diabetes. 1998;  47 1619-1624
    PubMedSuche in Google Scholar
  • 14 Abdel-Wahab Y HA, O"Harte F PM, Barnett C R, Flatt P R. Characterization of insulin glycation in insulin-secreting cells maintained in tissue culture.  J Endocrinol. 1997;  152 59-67
    CrossrefPubMedSuche in Google Scholar
  • 15 Abdel-Wahab Y HA, O’Harte F PM, Boyd A C, Barnett C R, Flatt P R. Glycation of insulin results in reduced biological activity in mice.  Acta Diabetol. 1997;  34 265-270
    CrossrefPubMedSuche in Google Scholar
  • 16 McKillop A M, Mooney M H, Harriott P, Flatt P R, O’Harte F PM. Evaluation of glycated insulin in diabetic animals using immunocytochemistry and radioimmunoassay.  Biochem Biophys Res Comm. 2001;  286 524-528
    CrossrefPubMedSuche in Google Scholar
  • 17 Lapolla A, Tessari P, Poli T, Valerio A, Duner E, Iori E, Fedele D, Crepaldi G. Reduced in vivo biological activity of in vitro glycosylated insulin.  Diabetes. 1988;  37 787-791
    PubMedSuche in Google Scholar
  • 18 Boyd A C, Abdel-Wahab Y HA, McKillop A M, McNulty H, Barnett C R, O’Harte F PM, Flatt P R. Impaired ability of glycated insulin to regulate plasma glucose and stimulate glucose transport and metabolism in mouse abdominal muscle.  Biochim Biophys Acta. 2000;  1519 128-134
    PubMedSuche in Google Scholar
  • 19 Hunter S J, Boyd A C, O’Harte F PM, McKillop A M, Wiggam M I, Ennis C N, Gamble R, Sheridan B, Barnett C R, McNulty H, Bell P M, Flatt P R. Demonstration of glycated insulin in human diabetic plasma and decreased biological activity assessed by euglycemic hyperinsulinemic clamp technique in man.  Diabetes. 2003;  52 492-498
    PubMedSuche in Google Scholar
  • 20 McKillop A M, McCluskey J T, Boyd A C, Mooney M H, Flatt P R, O'Harte F PM. Production and characterization of specific antibodies for evaluation of glycated insulin in plasma and biological tissues.  J Endocrinol. 2000;  167 153-163
    CrossrefPubMedSuche in Google Scholar
  • 21 Lindsay J R, McKillop A M, Mooney M H, O’Harte F PM, Bell P M, Flatt P R. Demonstration of elevated concentrations of circulating glycated insulin in human type 2 diabetes using a novel and specific radioimmunoassay.  Diabetologia. 2003;  46 475-478
    PubMedSuche in Google Scholar
  • 22 Lindsay J R, McKillop A M, Mooney M H, Flatt P R, Bell P M, O’Harte F PM. Meal-induced twenty-four hour profile of circulating glycated insulin in type 2 diabetic subjects measured by a novel radioimmunoassay.  Metabolism. 2003;  52 631-635
    CrossrefPubMedSuche in Google Scholar
  • 23 Salacinski P R, McLean C, Sykes J E, Clement-Jones V V, Lowry P J. Iodination of proteins, glycoproteins, and peptides using a solid-phase oxidizing agent, 1,3,4,6-tetrachloro-3 alpha, 6 alpha-diphenyl glycoluril (iodogen).  Anal Biochem. 1981;  117 136-146
    CrossrefPubMedSuche in Google Scholar
  • 24 Stevens J F. Determination of glucose by an automatic analyser.  Clin Chim Acta. 1971;  32 199-201
    CrossrefPubMedSuche in Google Scholar
  • 25 The Diabetes Control and Complications Trial Research Group . Diabetes Control and Complications Trial (DCCT): results of feasibility study.  Diabetes Care. 1987;  10 1-19
    CrossrefPubMedSuche in Google Scholar
  • 26 Abdel-Wahab Y HA, O’Harte F PM, Ratcliff H, McClenaghan N H, Barnett C R, Flatt P R. Glycation of insulin in the islets of Langerhans of normal and diabetic animals.  Diabetes. 1996;  45 1489-1496
    CrossrefPubMedSuche in Google Scholar
  • 27 Lindsay J R, McKillop A M, Mooney M H, O’Harte F PM, Flatt P R, Bell P M. The effect of nateglinide on the secretion of glycated insulin and glucose intolerance in type 2 diabetes.  Diabetic Research and Clinical Practice. 2003;  61 167-173
    PubMedSuche in Google Scholar
  • 28 Green B D, Gault V A, O’Harte , Flatt P R. Structurally modified analogues of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) as future antidiabetic agents.  Curr Pharm Des. 2004;  10 3651-3662
    CrossrefPubMedSuche in Google Scholar
  • 29 Rudovich N N, Rochlitz H J, Pfeiffer A F. Reduced hepatic insulin extraction in response to gastric inhibitory polypeptide compensates for reduced insulin secretion in normal-weight and normal glucose tolerant first-degree relatives of type 2 diabetic patients.  Diabetes. 2004;  53 2359-2365
    CrossrefPubMedSuche in Google Scholar

Dr. Aine M. McKillop

School of Biomedical Sciences · University of Ulster

Coleraine BT52 1SA · Northern Ireland

Telefon: +44(28)70-323066

Fax: +44(28)70-324965

eMail: am.mckillop@ulster.ac.uk