nach oben

Diabetologia

Erschienen in:

01.05.2012 | Article

Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion

verfasst von: J. Lau, J. Svensson, L. Grapensparr, Å. Johansson, P.-O. Carlsson

Erschienen in: Diabetologia | Ausgabe 5/2012

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

The blood perfusion of individual pancreatic islets is highly variable, with a subgroup of islets having high perfusion and blood vessels responsive to further blood flow increase induced by glucose. This study tested the hypothesis that there is heterogeneity between islets with regard to beta cell proliferation, function and gene expression based on differences in their blood perfusion.

Methods

Fluorescent microspheres were injected into the ascending aorta, and then microsphere-containing and non-microsphere-containing pancreatic islets were isolated for investigation. By this procedure, the 5% of islets with the greatest blood perfusion were identified for study. Islet endothelial cells were isolated separately to investigate the role of improved vascular support in the observed differences.

Results

The vascular network was found to be more dense and tortuous in microsphere-containing than other islets. The most highly blood-perfused islets also had a higher rate of beta cell proliferation, superior beta cell function and a markedly different gene expression from other islets. Cultured islets exposed to islet endothelial cell products had a similarly increased beta cell proliferation rate, yet significantly fewer changes in gene expression than observed in the most highly blood-perfused islets.

Conclusions/interpretation

A novel heterogeneity between islets was observed, with superior beta cell proliferation, function and gene expression in a subpopulation of islets identified by high blood perfusion. In contrast with a previously described population of low-oxygenated, sleeping islets, which are recruited into functionality when needed, the presently described heterogeneity is shown to remain in vitro after islet isolation.

Nur mit Berechtigung zugänglich

Bonner-Weir S, Orci L (1982) New perspectives on the microvasculature of the islets of Langerhans in the rat. Diabetes 31:883–889PubMedCrossRef

Nyman LR, Wells KS, Head WS et al (2008) Real-time, multidimensional in vivo imaging used to investigate blood flow in mouse pancreatic islets. J Clin Invest 118:3790–3797PubMedCrossRef

Lammert E, Cleaver O, Melton D (2001) Induction of pancreatic differentiation by signals from blood vessels. Science 294:564–567PubMedCrossRef

Nikolova G, Jabs N, Konstantinova I et al (2006) The vascular basement membrane: a niche for insulin gene expression and beta cell proliferation. Dev Cell 10:397–405PubMedCrossRef

Johansson A, Lau J, Sandberg M, Borg LA, Magnusson PU, Carlsson PO (2009) Endothelial cell signalling supports pancreatic beta cell function in the rat. Diabetologia 52:2385–2394PubMedCrossRef

Olerud J, Mokhtari D, Johansson M et al (2011) Thrombospondin-1: an islet endothelial cell signal of importance for {beta}-cell function. Diabetes 60:1946–1954PubMedCrossRef

Johansson M, Mattsson G, Andersson A, Jansson L, Carlsson PO (2006) Islet endothelial cells and pancreatic beta-cell proliferation: studies in vitro and during pregnancy in adult rats. Endocrinology 147:2315–2324PubMedCrossRef

Brunicardi FC, Stagner J, Bonner-Weir S et al (1996) Microcirculation of the islets of Langerhans. Long beach veterans administration regional medical education center symposium. Diabetes 45:385–392PubMed

Brissova M, Shostak A, Shiota M et al (2006) Pancreatic islet production of vascular endothelial growth factor-a is essential for islet vascularization, revascularization, and function. Diabetes 55:2974–2985PubMedCrossRef

10.

Jansson L (1996) Microsphere distribution in the pancreas of anesthetized rats. Alloxan stimulates the blood flow to all islets whereas glucose only affects the blood perfusion of a subgroup of islets. Int J Pancreatol 20:69–74PubMed

11.

Carlsson PO, Kallskog O, Bodin B, Andersson A, Jansson L (2002) Multiple injections of coloured microspheres for islet blood flow measurements in anaesthetised rats: influence of microsphere size. Ups J Med Sci 107:111–120PubMedCrossRef

12.

Carlsson PO, Jansson L, Ostenson CG, Kallskog O (1997) Islet capillary blood pressure increase mediated by hyperglycemia in NIDDM GK rats. Diabetes 46:947–952PubMedCrossRef

13.

Carlsson PO, Olsson R, Kallskog O, Bodin B, Andersson A, Jansson L (2002) Glucose-induced islet blood flow increase in rats: interaction between nervous and metabolic mediators. Am J Physiol Endocrinol Metab 283:E457–E464PubMed

14.

Nyman LR, Ford E, Powers AC, Piston DW (2010) Glucose-dependent blood flow dynamics in murine pancreatic islets in vivo. Am J Physiol Endocrinol Metab 298:E807–E814PubMedCrossRef

15.

Jansson L, Hellerstrom C (1983) Stimulation by glucose of the blood flow to the pancreatic islets of the rat. Diabetologia 25:45–50PubMedCrossRef

16.

Andersson A, Westman J, Hellerstrom C (1974) Effects of glucose on the ultrastructure and insulin biosynthesis of isolated mouse pancreatic islets maintained in tissue culture. Diabetologia 10:743–753PubMedCrossRef

17.

Weibel E (ed) (1979) Practical methods for biological morphometry. Academic Press, London

18.

Jackson CJ, Garbett PK, Nissen B, Schrieber L (1990) Binding of human endothelium to Ulex europaeus I-coated Dynabeads: application to the isolation of microvascular endothelium. J Cell Sci 96(Pt 2):257–262PubMed

19.

Mattsson G, Danielsson A, Kriz V, Carlsson PO, Jansson L (2006) Endothelial cells in endogenous and transplanted pancreatic islets: differences in the expression of angiogenic peptides and receptors. Pancreatology 6:86–95PubMedCrossRef

20.

Nyqvist D, Kohler M, Wahlstedt H, Berggren PO (2005) Donor islet endothelial cells participate in formation of functional vessels within pancreatic islet grafts. Diabetes 54:2287–2293PubMedCrossRef

21.

Andersson A (1974) Long-term effects of glucose on insulin release and glucose oxidation by mouse pancreatic islets maintained in tissue culture. Biochem J 140:377–382PubMed

22.

Lammert E, Gu G, McLaughlin M et al (2003) Role of VEGF-A in vascularization of pancreatic islets. Curr Biol 13:1070–1074PubMedCrossRef

23.

Kamba T, Tam BY, Hashizume H et al (2006) VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol 290:H560–H576PubMedCrossRef

24.

Nakatsu MN, Sainson RC, Perez-del-Pulgar S et al (2003) VEGF(121) and VEGF(165) regulate blood vessel diameter through vascular endothelial growth factor receptor 2 in an in vitro angiogenesis model. Lab Invest 83:1873–1885PubMedCrossRef

25.

Virtanen I, Banerjee M, Palgi J et al (2008) Blood vessels of human islets of Langerhans are surrounded by a double basement membrane. Diabetologia 51:1181–1191PubMedCrossRef

26.

Marcheva B, Ramsey KM, Buhr ED et al (2010) Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature 466:627–631PubMedCrossRef

27.

Du A, Hunter CS, Murray J et al (2009) Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas. Diabetes 58:2059–2069PubMedCrossRef

28.

Pipeleers DG (1992) Heterogeneity in pancreatic beta-cell population. Diabetes 41:777–781PubMedCrossRef

29.

Pipeleers D, Kiekens R, Ling Z, Wilikens A, Schuit F (1994) Physiologic relevance of heterogeneity in the pancreatic beta-cell population. Diabetologia 37(Suppl 2):S57–S64PubMedCrossRef

30.

Olsson R, Carlsson PO (2011) A low-oxygenated subpopulation of pancreatic islets constitutes a functional reserve of endocrine cells. Diabetes 60:2068–2075PubMedCrossRef

31.

Sato Y, Endo H, Okuyama H et al (2011) Cellular hypoxia of pancreatic beta-cells due to high levels of oxygen consumption for insulin secretion in vitro. J Biol Chem 286:12524–12532PubMedCrossRef

32.

Lyssenko V, Jonsson A, Almgren P et al (2008) Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med 359:2220–2232PubMedCrossRef

33.

Scott LJ, Mohlke KL, Bonnycastle LL et al (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341–1345PubMedCrossRef

34.

Gloyn AL, Pearson ER, Antcliff JF et al (2004) Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med 350:1838–1849PubMedCrossRef

35.

Reinbothe TM, Ivarsson R, Li DQ et al (2009) Glutaredoxin-1 mediates NADPH-dependent stimulation of calcium-dependent insulin secretion. Mol Endocrinol 23:893–900PubMedCrossRef

36.

Itoh Y, Kawamata Y, Harada M et al (2003) Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 422:173–176PubMedCrossRef

37.

Nagasumi K, Esaki R, Iwachidow K et al (2009) Overexpression of GPR40 in pancreatic beta-cells augments glucose-stimulated insulin secretion and improves glucose tolerance in normal and diabetic mice. Diabetes 58:1067–1076PubMedCrossRef

38.

Alquier T, Peyot ML, Latour MG et al (2009) Deletion of GPR40 impairs glucose-induced insulin secretion in vivo in mice without affecting intracellular fuel metabolism in islets. Diabetes 58:2607–2615PubMedCrossRef

39.

Raum JC, Gerrish K, Artner I et al (2006) FoxA2, Nkx2.2, and PDX-1 regulate islet beta-cell-specific mafA expression through conserved sequences located between base pairs −8118 and −7750 upstream from the transcription start site. Mol Cell Biol 26:5735–5743PubMedCrossRef

40.

Dutta S, Bonner-Weir S, Montminy M, Wright C (1998) Regulatory factor linked to late-onset diabetes? Nature 392:560PubMedCrossRef

41.

Zhang C, Moriguchi T, Kajihara M et al (2005) MafA is a key regulator of glucose-stimulated insulin secretion. Mol Cell Biol 25:4969–4976PubMedCrossRef

42.

Aguayo-Mazzucato C, Koh A, El Khattabi I et al (2011) Mafa expression enhances glucose-responsive insulin secretion in neonatal rat beta cells. Diabetologia 54:583–593PubMedCrossRef

43.

Shimohata H, Yoh K, Morito N, Shimano H, Kudo T, Takahashi S (2006) MafK overexpression in pancreatic beta-cells caused impairment of glucose-stimulated insulin secretion. Biochem Biophys Res Commun 346:671–680PubMedCrossRef

44.

Artner I, Hang Y, Mazur M et al (2010) MafA and MafB regulate genes critical to beta-cells in a unique temporal manner. Diabetes 59:2530–2539PubMedCrossRef

45.

Schisler JC, Jensen PB, Taylor DG et al (2005) The Nkx6.1 homeodomain transcription factor suppresses glucagon expression and regulates glucose-stimulated insulin secretion in islet beta cells. Proc Natl Acad Sci U S A 102:7297–7302PubMedCrossRef

46.

Schuit F, Moens K, Heimberg H, Pipeleers D (1999) Cellular origin of hexokinase in pancreatic islets. J Biol Chem 274:32803–32809PubMedCrossRef

47.

German MS (1993) Glucose sensing in pancreatic islet beta cells: the key role of glucokinase and the glycolytic intermediates. Proc Natl Acad Sci U S A 90:1781–1785PubMedCrossRef

48.

Heimberg H, de Vos A, Vandercammen A, van Schaftingen E, Pipeleers D, Schuit F (1993) Heterogeneity in glucose sensitivity among pancreatic beta-cells is correlated to differences in glucose phosphorylation rather than glucose transport. EMBO J 12:2873–2879PubMed

49.

Konstantinova I, Nikolova G, Ohara-Imaizumi M et al (2007) EphA-Ephrin-A-mediated beta cell communication regulates insulin secretion from pancreatic islets. Cell 129:359–370PubMedCrossRef

50.

Borromeo CM, Pottier X, In’t Veld PA et al (2005) Heterogeneity in distribution of amyloid-positive islets in type-2 diabetic patients. Virchows Arch 446:232–238PubMedCrossRef

Titel: Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion
verfasst von: J. Lau
J. Svensson
L. Grapensparr
Å. Johansson
P.-O. Carlsson
Publikationsdatum: 01.05.2012
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 5/2012
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-012-2476-6

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

25.04.2024 | Hypotonie | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Update Innere Medizin

Springer Medizin

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2012

The secretion pattern of perivascular fat cells is different from that of subcutaneous and visceral fat cells

The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes

Hyperglycaemia normalises insulin action on glucose metabolism but not the impaired activation of AKT and glycogen synthase in the skeletal muscle of patients with type 2 diabetes

Risk of breast cancer in patients on long-acting insulin analogues in comparison with those on human insulin

Effect of exercise training on insulin sensitivity, mitochondria and computed tomography muscle attenuation in overweight women with and without polycystic ovary syndrome

Descriptive epidemiology of type 1 diabetes—is it still in?

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Update Innere Medizin