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; S. Mohanty; M. Niessen; G. A. Spinas; T. Trüb

doi:10.1055/s-2005-865803

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

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

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

Full Text

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
2 Amasino R M. Acceleration of nucleic acid hybridization rate by polyethylene glycol. Anal Biochem. 1986; 152 304-307
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
4 Ashcroft S J. Glucoreceptor mechanisms and the control of insulin release and biosynthesis. Diabetologia. 1980; 18 5-15
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
6 Bernard-Kargar C, Ktorza A. Endocrine pancreas plasticity under physiological and pathological conditions. Diabetes. 2001; 50 (Suppl 1) S30-S35
7 Bonner-Weir S. Islet growth and development in the adult. J Mol Endocrinol. 2000; 24 297-302
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
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;
10 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987; 162 156-159
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
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
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
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
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
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
17 King D L, Chick W L. Pancreatic beta cell replication: effects of hexose sugars. Endocrinology. 1976; 99 1003-1009
18 King D L, Kitchen K C, Chick W L. Pancreatic beta-cell replication: relation to insulin secretion. Endocrinology. 1978; 103 1321-1327
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
20 Laemmli U K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227 680-685
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
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
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
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
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
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
27 Oyadomari S, Araki E, Mori M. Endoplasmic reticulum stress-mediated apoptosis in pancreatic β-cells. Apoptosis. 2002; 7 335-345
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
29 Pirola L, Johnston A M, Van Obberghen E. Modulation of insulin action. Diabetologia. 2004; 47 170-184
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
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
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
33 Swenne I. Pancreatic beta-cell growth and diabetes mellitus. Diabetologia. 1992; 35 193-201
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
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
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
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

1 Authors contributed equally to this work.

Markus Niessen

Division of Endocrinology and Diabetes
University Hospital

Zurich

Switzerland

Phone: + 41442552225

Fax: + 41 4 42 55 97 41

Email: markus.niessen@usz.ch