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. 1992 Oct;90(4):1361–1369. doi: 10.1172/JCI116002

Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts.

M D Menger 1, P Vajkoczy 1, R Leiderer 1, S Jäger 1, K Messmer 1
PMCID: PMC443181  PMID: 1401071

Abstract

The influence of hyperglycemia on the microvascular blood perfusion of pancreatic islet isografts of Syrian golden hamsters was analyzed by direct visualization of the islet's microvasculature by means of in vivo fluorescence microscopy. The experiments were performed using the hamster dorsal skinfold preparation, which allows for quantitative analysis of the microcirculation of islets grafted on the striated skin muscle. Islets were isolated from inbred hamsters by collagenase digestion and subsequently transplanted in normoglycemic (controls; n = 8) and hyperglycemic (65 mg/kg streptozotocin intravenously; n = 10) recipients. In both groups, revascularization of the islet grafts was completed on day 10 after transplantation. Quantitative analysis of capillary blood perfusion on days 6, 10, and 14 revealed no differences in functional capillary density and capillary red blood cell velocity of islets grafted into normoglycemic as compared to hyperglycemic animals. However, islet capillaries were significantly wider in hyperglycemic recipients (11.9 +/- 1.3 microns, P < 0.01) as compared to normoglycemic controls (8.9 +/- 0.4 microns). The increase of capillary diameters resulted in a significant rise (P < 0.01) of mean capillary blood perfusion from 1.76 +/- 0.39 nl/min in controls to 2.88 +/- 0.63 nl/min in hyperglycemic recipients, indicating an increase in microvascular blood perfusion due to hyperglycemia. From these results it is concluded that hyperglycemia is associated with higher capillary blood perfusion in revascularized islet isografts, similarly as known for pancreatic islets in situ.

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Selected References

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  1. Baker M., Wayland H. On-line volume flow rate and velocity profile measurement for blood in microvessels. Microvasc Res. 1974 Jan;7(1):131–143. doi: 10.1016/0026-2862(74)90043-0. [DOI] [PubMed] [Google Scholar]
  2. Buckberg G. D., Luck J. C., Payne D. B., Hoffman J. I., Archie J. P., Fixler D. E. Some sources of error in measuring regional blood flow with radioactive microspheres. J Appl Physiol. 1971 Oct;31(4):598–604. doi: 10.1152/jappl.1971.31.4.598. [DOI] [PubMed] [Google Scholar]
  3. Bunnag S. C., Warner N. E., Bunnag S. Vasomotor reactions in the islets affecting the blood glucose levels. Bibl Anat. 1977;(16 Pt 2):445–449. [PubMed] [Google Scholar]
  4. Endrich B., Asaishi K., Götz A., Messmer K. Technical report--a new chamber technique for microvascular studies in unanesthetized hamsters. Res Exp Med (Berl) 1980;177(2):125–134. doi: 10.1007/BF01851841. [DOI] [PubMed] [Google Scholar]
  5. Finch D. R., Wise P. H., Morris P. J. Successful intra-splenic transplantation of syngeneic and allogeneic isolated pancreatic islets. Diabetologia. 1977 May;13(3):195–199. doi: 10.1007/BF01219699. [DOI] [PubMed] [Google Scholar]
  6. Gray B. N., Watkins E., Jr Isolated islet transplantation in experimental diabetes. Aust J Exp Biol Med Sci. 1976 Feb;54(1):57–70. doi: 10.1038/icb.1976.6. [DOI] [PubMed] [Google Scholar]
  7. Gray D. W., McShane P., Morris P. J. The effect of hyperglycemia on isolated rodent islets transplanted to the kidney capsule site. Transplantation. 1986 Jun;41(6):699–703. doi: 10.1097/00007890-198606000-00006. [DOI] [PubMed] [Google Scholar]
  8. Gray D. W., Morris P. J. Developments in isolated pancreatic islet transplantation. Transplantation. 1987 Mar;43(3):321–331. doi: 10.1097/00007890-198703000-00001. [DOI] [PubMed] [Google Scholar]
  9. Griffith R. C., Scharp D. W., Hartman B. K., Ballinger W. F., Lacy P. E. A morphologic study of intrahepatic portal-vein islet isografts. Diabetes. 1977 Mar;26(3):201–214. doi: 10.2337/diab.26.3.201. [DOI] [PubMed] [Google Scholar]
  10. Gylfe E., Hellman B. The heat production of pancreatic beta-cells stimulated by glucose. Acta Physiol Scand. 1975 Feb;93(2):179–183. doi: 10.1111/j.1748-1716.1975.tb05807.x. [DOI] [PubMed] [Google Scholar]
  11. HELLERSTROM C., HELLMAN B. The blood circulation in the islets of Langerhans visualized by the fluorescent dye vasoflavine. Studies in normal and obese-hyperglycemic mice. Acta Soc Med Ups. 1961;66:88–94. [PubMed] [Google Scholar]
  12. Hellerström C. Effects of carbohydrates on the oxygen consumption of isolated pancreatic islets of mice. Endocrinology. 1967 Jul;81(1):105–112. doi: 10.1210/endo-81-1-105. [DOI] [PubMed] [Google Scholar]
  13. Jansson L., Hellerström C. Glucose-induced changes in pancreatic islet blood flow mediated by central nervous system. Am J Physiol. 1986 Dec;251(6 Pt 1):E644–E647. doi: 10.1152/ajpendo.1986.251.6.E644. [DOI] [PubMed] [Google Scholar]
  14. Jansson L., Hellerström C. Stimulation by glucose of the blood flow to the pancreatic islets of the rat. Diabetologia. 1983 Jul;25(1):45–50. doi: 10.1007/BF00251896. [DOI] [PubMed] [Google Scholar]
  15. Jansson L., Sandler S. Influence of hyperglycemia on blood perfusion of autotransplanted pancreatic islets in diabetic rats. Diabetes. 1989 Jan;38 (Suppl 1):196–198. doi: 10.2337/diab.38.1.s196. [DOI] [PubMed] [Google Scholar]
  16. Jansson L., Sandler S. Pancreatic islet circulation in relation to the diabetogenic action of streptozotocin in the rat. Endocrinology. 1985 Mar;116(3):896–900. doi: 10.1210/endo-116-3-896. [DOI] [PubMed] [Google Scholar]
  17. KRACHT J., LO Y. C., RALL J. [On relations between the Island capillaries and B cell function]. Endokrinologie. 1960 Mar;39:35–43. [PubMed] [Google Scholar]
  18. Kemp C. B., Knight M. J., Scharp D. W., Ballinger W. F., Lacy P. E. Effect of transplantation site on the results of pancreatic islet isografts in diabetic rats. Diabetologia. 1973 Dec;9(6):486–491. doi: 10.1007/BF00461694. [DOI] [PubMed] [Google Scholar]
  19. Lacy P. E., Kostianovsky M. Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes. 1967 Jan;16(1):35–39. doi: 10.2337/diab.16.1.35. [DOI] [PubMed] [Google Scholar]
  20. Latif Z. A., Noel J., Alejandro R. A simple method of staining fresh and cultured islets. Transplantation. 1988 Apr;45(4):827–830. [PubMed] [Google Scholar]
  21. Lipowsky H. H., Zweifach B. W. Application of the "two-slit" photometric technique to the measurement of microvascular volumetric flow rates. Microvasc Res. 1978 Jan;15(1):93–101. doi: 10.1016/0026-2862(78)90009-2. [DOI] [PubMed] [Google Scholar]
  22. Menger M. D., Jaeger S., Walter P., Feifel G., Hammersen F., Messmer K. Angiogenesis and hemodynamics of microvasculature of transplanted islets of Langerhans. Diabetes. 1989 Jan;38 (Suppl 1):199–201. doi: 10.2337/diab.38.1.s199. [DOI] [PubMed] [Google Scholar]
  23. Menger M. D., Jäger S., Walter P., Hammersen F., Messmer K. A novel technique for studies on the microvasculature of transplanted islets of Langerhans in vivo. Int J Microcirc Clin Exp. 1990 Feb;9(1):103–117. [PubMed] [Google Scholar]
  24. Menger M. D., Jäger S., Walter P., Messmer K. Influence of culture temperature (24 degrees C/37 degrees C) on revascularization of transplanted islets of Langerhans in the Syrian hamster. Transplant Proc. 1990 Apr;22(2):823–823. [PubMed] [Google Scholar]
  25. Menger M. D., Jäger S., Walter P., Messmer K. Influence of hyperglycemia on the process of angiogenesis and revascularization of freely transplanted islets of Langerhans. Transplant Proc. 1990 Apr;22(2):821–822. [PubMed] [Google Scholar]
  26. Menger M. D., Wolf B., Höbel R., Schorlemmer H. U., Messmer K. Microvascular phenomena during pancreatic islet graft rejection. Langenbecks Arch Chir. 1991;376(4):214–221. doi: 10.1007/BF00186815. [DOI] [PubMed] [Google Scholar]
  27. Reece-Smith H., Du Toit D. F., McShane P., Morris P. J. Prolonged survival of pancreatic islet allografts transplanted beneath the renal capsule. Transplantation. 1981 Apr;31(4):305–306. [PubMed] [Google Scholar]
  28. Rooth P., Dawidson I., Lafferty K., Diller K., Armstrong J., Pratt P., Simonsen R., Täljedal I. B. Prevention of detrimental effect of cyclosporin A on vascular ingrowth of transplanted pancreatic islets with verapamil. Diabetes. 1989 Jan;38 (Suppl 1):202–205. doi: 10.2337/diab.38.1.s202. [DOI] [PubMed] [Google Scholar]
  29. Rooth P., Täljedal I. B. Vital microscopy of islet blood flow: catecholamine effects in normal and ob/ob mice. Am J Physiol. 1987 Jan;252(1 Pt 1):E130–E135. doi: 10.1152/ajpendo.1987.252.1.E130. [DOI] [PubMed] [Google Scholar]
  30. Sandler S., Jansson L. Blood flow measurements in autotransplanted pancreatic islets of the rat. Impairment of the blood perfusion of the graft during hyperglycemia. J Clin Invest. 1987 Jul;80(1):17–21. doi: 10.1172/JCI113044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Selawry H. P., Mui M. M., Paul R. D., Distasio J. A. Improved allograft survival using highly enriched populations of rat islets. Transplantation. 1984 Feb;37(2):202–205. doi: 10.1097/00007890-198402000-00016. [DOI] [PubMed] [Google Scholar]
  32. Stagner J. I., Samols E. The induction of capillary bed development by endothelial cell growth factor before islet transplantation may prevent islet ischemia. Transplant Proc. 1990 Apr;22(2):824–828. [PubMed] [Google Scholar]
  33. Sutherland D. E., Rynasiewicz J. J., Kawahara K., Gorecki P., Najarian J. S. Rejection of islets versus immediately vascularized pancreatic allografts: a quantitative comparison. J Surg Res. 1980 Sep;29(3):240–247. doi: 10.1016/0022-4804(80)90167-5. [DOI] [PubMed] [Google Scholar]

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