Exp Clin Endocrinol Diabetes 2001; Vol. 109(2): 116-119
DOI: 10.1055/s-2001-14828
Articles

© Johann Ambrosius Barth

Macroencapsulation of rat islets without alteration of insulin secretion kinetics

N. Lembert 1 , J. Wesche 1 , P. Petersen 2 , P. Zschocke 3 , A. Enderle 3 , H. Planck 3 , H. P. T. Ammon 1
  • 1 Department of Pharmacology, University of Tübingen, Germany
  • 2 Department of General Surgery, University of Tübingen, Germany
  • 3 Institute of Textile and Process Engineering (ITV), Denkendorf, Germany
Further Information

Publication History

Publication Date:
31 December 2001 (online)

Summary:

Transplantation of encapsulated islets may restore endogenous insulin secretion in type 1 diabetics with no need of lifetime immunosuppression of the recipient. A biomaterial should be developed which combined immunoisolation with rapid and efficient diffusion of glucose and insulin. Rat islets were macroencapsulated in capillaries (molecular cut off 50 kD) of differently modified polysulphone. Macroencapsulated islets were perifused to study the kinetics of glucose induced insulin secretion into the perifusion medium. Blending polysulphone (PSU) with poly vinyl pyrrolidone or sodium dodecyl sulphate was not suited for islet macroencapsulation since glucose induced insulin release was absent after encapsulation. Hydroxy methylation (CH2OH) of PSU improved the secretory behaviour of macroencapsulated islets depending on the degree of substitution (DS). At 0.8 DS glucose induced insulin secretion was delayed and inefficient. At maximal degrees of PSU-substitution (1.8) the kinetics of insulin release and the efficiency of insulin release were very similar to that observed of free floating islets. In conclusion, highly substituted hydroxy methylated polysulphone allows a rapid and efficient insulin release after macroencapsulation and is suited for the further development of a bioartificial pancreas.

References

  • 1 Calafiore R. Actual perspectives in biohybrid artificial pancreas for the therapy of type 1, insulin-dependent diabetes mellitus.  Diabetes Metab Rev. 315-324 1998; 
  • 2 Calles-Escandon J, Robbins D C. Loss of early phase of insulin release in humans impairs glucose tolerance and blunts thermic effect of glucose.  Diabetes. 36 1167-1172 1987; 
  • 3 DCCT Research Group . The effect of intensive treatment of diabetes an the development and progression of long-term complications in insulin-dependent diabetes mellitus.  N Engl J Med. 329 977-986 1993; 
  • 4 Gruessner A C, Sutherland D E. Pancreas transplants for the United states (US) and non-US cases as reported to the international pancreas transplant registry (IPTR) and to the united network for organ sharing (UNOS).  Clin Transpl. 45-49 1997; 
  • 5 Lacy P E, Kostianovsky M. Method for the isolation of intact islets of Langerhans from the rat pancreas.  Diabetes. 16 35-39 1967; 
  • 6 Maki T, Logde J P, Caretta M, Ohzato H, Borland K M, Sullivan S J, Staruk J, Muller T E, Solomon B A, Chick W L, Monaco A P. Treatment of severe diabetes mellitus for more than one year using a vascularized hybrid artificial pancreas.  Transplantation. 55 713-718 1993; 
  • 7 Maki T, Otsu I, O'Neil J J, Dunleavy K, Mullon J P, Solomon B A, Monaco A P. Treatment of diabetes by xenogenic islets without immunosuppression. Use of a vascularized bioartificial pancreas.  Diabetes. 45 342-347 1996; 
  • 8 Shapiro A MJ, Lakey J RT, Ryan E A, Korbutt G S, Toth E, Warnock G L, Kneteman N M, Rajotte R V. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen.  N Engl J Med. 343 230-238 2000; 
  • 9 Sullivan S J, Maki T, Borland K M, Mahoney M D, Solomon B A, Muller T E, Monaco A T, Chick W L. Biohybrid artificial pancreas: Longterm implantation studies in diabetic, pancreatectomized dogs.  Science. 252 718-721 1991; 

Dr. Nicolas Lembert

Department of Pharmacology

University of Tübingen

Auf der Morgenstelle 8

D-72076 Tübingen

Germany

Phone: + 49-7071-29 72471

Fax: + 49-7071-29 2476

Email: nicolas.lembert@uni-tuebingen.de