PDF herunterladen
Exp Clin Endocrinol Diabetes 2005; 113(8): 423-429
DOI: 10.1055/s-2005-865803
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

The Metabolisable Hexoses D-Glucose and D-Mannose Enhance the Expression of IRS-2 but not of IRS-1 in Pancreatic β-Cells

I. Amacker-Françoys[*] 1 , S. Mohanty[*] 1 , M. Niessen1 , G. A. Spinas1 , T. Trüb2
  • 1Division of Endocrinology and Diabetes, University Hospital, Zurich, Switzerland
  • 2Department for Equipment and Logistics, University Zürich, Zürich, Switzerland
Weitere Informationen

Publikationsverlauf

Received: May 2, 2005 First decision: May 29, 2005

Accepted: June 5, 2005

Publikationsdatum:
08. September 2005 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

D-glucose regulates maintenance and function of pancreatic β-cells. Several studies have shown that IRS-2, but not IRS-1, is necessary to maintain and sufficient to expand functional β-cell mass. We therefore analyzed the expression of IRS-2 and IRS-1 in β-cells after culture in the presence of various concentrations of D-glucose and other metabolisable or non-metabolisable hexoses. D-glucose increased Irs-2 transcription and IRS-2 accumulation in a dose-dependent manner (1.6 to 25 mmol/l), with a 3-fold increased plateau after 10 h. In contrast, the expression of IRS-1 remained unaffected. D-glucose also induced phosphorylation of IRS-2 while non-metabolisable hexoses did neither affect expression nor phosphorylation. D-glucose-mediated elevation and phosphorylation of IRS-2 were independent of autocrine insulin action although insulin itself could transiently and slightly enhance IRS-2 expression.

Key words

IRS-2 - diabetes - β-cells - pancreatic islets

References

  • 1 Alonso S, Minty A, Bourlet Y, Buckingham M. Comparison of three actin-coding sequences in the mouse; evolutionary relationships between the actin genes of warm-blooded vertebrates.  J Mol Evol. 1986;  23 11-22
    PubMedGoogle Scholar
  • 2 Amasino R M. Acceleration of nucleic acid hybridization rate by polyethylene glycol.  Anal Biochem. 1986;  152 304-307
    CrossrefPubMedGoogle Scholar
  • 3 Asfari M, Janjic D, Meda P, Li G, Halban P A, Wollheim C B. Establishment of 2-mercaptoethanol-dependent differentiated insulin- secreting cell lines.  Endocrinology. 1992;  130 167-178
    CrossrefPubMedGoogle Scholar
  • 4 Ashcroft S J. Glucoreceptor mechanisms and the control of insulin release and biosynthesis.  Diabetologia. 1980;  18 5-15
    CrossrefPubMedGoogle Scholar
  • 5 Ashcroft S J, Weerasinghe L C, Randle P J. Interrelationship of islet metabolism, adenosine triphosphate content and insulin release.  Biochem J. 1973;  132 223-231
    PubMedGoogle Scholar
  • 6 Bernard-Kargar C, Ktorza A. Endocrine pancreas plasticity under physiological and pathological conditions.  Diabetes. 2001;  50 (Suppl 1) S30-S35
    PubMedGoogle Scholar
  • 7 Bonner-Weir S. Islet growth and development in the adult.  J Mol Endocrinol. 2000;  24 297-302
    CrossrefPubMedGoogle Scholar
  • 8 Bonner-Weir S, Deery D, Leahy J L, Weir G C. Compensatory growth of pancreatic beta-cells in adult rats after short-term glucose infusion.  Diabetes. 1989;  38 49-53
    CrossrefPubMedGoogle Scholar
  • 9 Briaud I, Dickson L M, Lingohr M K, McCuaig J F, Lawrence J C, Rhodes C J. IRS-2 proteasomal degradation mediated by a mTOR-induced negative feedback downregulates PKB-mediated signaling pathway in beta-cells.  J Biol Chem. 2004; 
    PubMedGoogle Scholar
  • 10 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.  Anal Biochem. 1987;  162 156-159
    PubMedGoogle Scholar
  • 11 Cousin S P, Hügl S R, Myers J M, White M F, Reifel-Miller A, Rhodes C J. Stimulation of pancreatic beta-cell proliferation by growth hormone is glucose-dependent: signal transduction via Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) with no crosstalk to insulin receptor substrate-mediated mitogenic signalling.  Biochem J. 1999;  344 649-658
    CrossrefPubMedGoogle Scholar
  • 12 Hennige A M, Burks D J, Ozcan U, Kulkarni R N, Ye J, Park S, Schubert M, Fisher T L, Dow M A, Leshan R, Zakaria M, Mossa-Basha M, White M F. Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetes.  J Clin Invest. 2003;  112 1521-1532
    CrossrefPubMedGoogle Scholar
  • 13 Hoorens A, Van de C M, Kloppel G, Pipeleers D. Glucose promotes survival of rat pancreatic beta cells by activating synthesis of proteins which suppress a constitutive apoptotic program.  J Clin Invest. 1996;  98 1568-1574
    PubMedGoogle Scholar
  • 14 Hügl S R, White M F, Rhodes C J. Insulin-like growth factor I (IGF-I)-stimulated pancreatic beta-cell growth is glucose-dependent. Synergistic activation of insulin receptor substrate-mediated signal transduction pathways by glucose and IGF-I in INS-1 cells.  J Biol Chem. 1998;  273 17771-17779
    CrossrefPubMedGoogle Scholar
  • 15 Jhala U S, Canettieri G, Screaton R A, Kulkarni R N, Krajewski S, Reed J, Walker J, Lin X, White M, Montminy M. cAMP promotes pancreatic {beta}-cell survival via CREB-mediated induction of IRS2.  Genes Dev. 2003;  17 1575-1580
    CrossrefPubMedGoogle Scholar
  • 16 Kekow J, Ulrichs K, Muller-Ruchholtz W, Gross W L. Measurement of rat insulin. Enzyme-linked immunosorbent assay with increased sensitivity, high accuracy, and greater practicability than established radioimmunoassay.  Diabetes. 1988;  37 321-326
    PubMedGoogle Scholar
  • 17 King D L, Chick W L. Pancreatic beta cell replication: effects of hexose sugars.  Endocrinology. 1976;  99 1003-1009
    PubMedGoogle Scholar
  • 18 King D L, Kitchen K C, Chick W L. Pancreatic beta-cell replication: relation to insulin secretion.  Endocrinology. 1978;  103 1321-1327
    PubMedGoogle Scholar
  • 19 Kubota N, Tobe K, Terauchi Y, Eto K, Yamauchi T, Suzuki R, Tsubamoto Y, Komeda K, Nakano R, Miki H, Satoh S, Sekihara H, Sciacchitano S, Lesniak M, Aizawa S, Nagai R, Kimura S, Akanuma Y, Taylor S I, Kadowaki T. Disruption of insulin receptor substrate 2 causes type 2 diabetes because of liver insulin resistance and lack of compensatory beta-cell hyperplasia.  Diabetes. 2000;  49 1880-1889
    CrossrefPubMedGoogle Scholar
  • 20 Laemmli U K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.  Nature. 1970;  227 680-685
    PubMedGoogle Scholar
  • 21 Leahy J L, Weir G C. Beta-cell dysfunction in hyperglycaemic rat models: recovery of glucose-induced insulin secretion with lowering of the ambient glucose level.  Diabetologia. 1991;  34 640-647
    CrossrefPubMedGoogle Scholar
  • 22 Ling Z, Kiekens R, Mahler T, Schuit F C, Pipeleers-Marichal M, Sener A, Kloppel G, Malaisse W J, Pipeleers D G. Effects of chronically elevated glucose levels on the functional properties of rat pancreatic beta-cells.  Diabetes. 1996;  45 1774-1782
    PubMedGoogle Scholar
  • 23 Liu K, Paterson A J, Chin E, Kudlow J E. Glucose stimulates protein modification by O-linked GlcNAc in pancreatic beta cells: linkage of O-linked GlcNAc to beta cell death.  Proc Natl Acad Sci USA. 2000;  97 2820-2825
    CrossrefPubMedGoogle Scholar
  • 24 Maedler K, Spinas G A, Lehmann R, Sergeev P, Weber M, Fontana A, Kaiser N, Donath M Y. Glucose induces beta-cell apoptosis via upregulation of the Fas receptor in human islets.  Diabetes. 2001;  50 1683-1690
    CrossrefPubMedGoogle Scholar
  • 25 Mohanty S, Spinas G A, Maedler K, Zuellig R A, Lehmann R, Donath M Y, Trub T, Niessen M. Overexpression of IRS2 in isolated pancreatic islets causes proliferation and protects human beta-cells from hyperglycemia-induced apoptosis.  Exp Cell Res. 2005;  303 68-78
    CrossrefPubMedGoogle Scholar
  • 26 Okazaki T, Ishikawa T, Nishimori S, Igarashi T, Hata K, Fujita T. Hyperosmolarity-induced gene stimulation is mediated by the negative calcium responsive element.  J Biol Chem. 1997;  272 32274-32279
    CrossrefPubMedGoogle Scholar
  • 27 Oyadomari S, Araki E, Mori M. Endoplasmic reticulum stress-mediated apoptosis in pancreatic β-cells.  Apoptosis. 2002;  7 335-345
    CrossrefPubMedGoogle Scholar
  • 28 Ozcan U, Cao Q, Yilmaz E, Lee A H, Iwakoshi N N, Ozdelen E, Tuncman G, Gorgun C, Glimcher L H, Hotamisligil G S. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes.  Science. 2004;  306 (5695) 457-461
    CrossrefPubMedGoogle Scholar
  • 29 Pirola L, Johnston A M, Van Obberghen E. Modulation of insulin action.  Diabetologia. 2004;  47 170-184
    CrossrefPubMedGoogle Scholar
  • 30 Ristow M, Mulder H, Pomplun D, Schulz T, Muller-Schmehl K, Krause A, Fex M, Puccio H, Muller J, Isken F, Spranger J, Muller-Wieland D, Magnuson M A, Mohlig M, Koenig M, Pfeiffer A FH. Frataxin deficiency in pancreatic islets causes diabetes due to loss of beta cell mass.  J Clin Invest. 2003;  112 527-534
    CrossrefPubMedGoogle Scholar
  • 31 Schuppin G T, Pons S, Hügl S R, Aiello L P, King G L, White M F, Rhodes C J. A specific increased expression of insulin receptor substrate 2 in pancreatic beta-cell lines is involved in mediating serum-stimulated beta-cell growth.  Diabetes. 1998;  47 1074-1085
    PubMedGoogle Scholar
  • 32 Sun X J, Wang L M, Zhang Y, Yenush L, Myers Jr M G, Glasheen E, Lane W S, Pierce J H, White M F. Role of IRS-2 in insulin and cytokine signalling.  Nature. 1995;  377 173-177
    CrossrefPubMedGoogle Scholar
  • 33 Swenne I. Pancreatic beta-cell growth and diabetes mellitus.  Diabetologia. 1992;  35 193-201
    CrossrefPubMedGoogle Scholar
  • 34 Webster H V, Bone A J, Webster K A, Wilkin T J. Comparison of an enzyme-linked immunosorbent assay (ELISA) with a radioimmunoassay (RIA) for the measurement of rat insulin.  J Immunol Methods. 1990;  134 95-100
    CrossrefPubMedGoogle Scholar
  • 35 Withers D J, Burks D J, Towery H H, Altamuro S L, Flint C L, White M F. IRS-2 coordinates IGF-1 receptor-mediated beta-cell development and peripheral insulin signalling.  Nat Genet. 1999;  23 32-40
    PubMedGoogle Scholar
  • 36 Withers D J, Gutierrez J S, Towery H, Burks D J, Ren J M, Previs S, Zhang Y, Bernal D, Pons S, Shulman G I, Bonner-Weir S, White M F. Disruption of IRS-2 causes type 2 diabetes in mice.  Nature. 1998;  391 900-904
    CrossrefPubMedGoogle Scholar
  • 37 Yamamoto T, Asano T, Mori A, Kumai C, Okumura M, Soji T. A rapid method for the separation of rat pancreatic islets from collagenase-digested pancreas using Percoll.  Endocrinol Jpn. 1981;  28 563-567
    PubMedGoogle Scholar

1 Authors contributed equally to this work.

Markus Niessen

Division of Endocrinology and Diabetes
University Hospital

Zurich

Switzerland

Telefon: + 41442552225

Fax: + 41 4 42 55 97 41

eMail: markus.niessen@usz.ch