J Korean Med Sci.  2010 Feb;25(2):203-210. 10.3346/jkms.2010.25.2.203.

Comparison of Four Pancreatic Islet Implantation Sites

• Kim HI
• Yu JE
• Park CG
• Kim SJ

• KMID: 1779248
• DOI: http://doi.org/10.3346/jkms.2010.25.2.203

Abstract

Although the liver is the most common site for pancreatic islet transplantation, it is not optimal. We compared kidney, liver, muscle, and omentum as transplantation sites with regard to operative feasibility, and the efficiency of implantation and glycemic control. Islets from C57BL/6 mice were transplanted into diabetic syngeneic recipients. The mean operative time and mortality were measured to assess feasibility. To assess implantation efficiency, the marginal mass required to cure diabetes and the mean time taken to achieve normoglycemia were measured. A glucose tolerance test was performed to assess glycemic control efficiency. The data are listed in the order of the kidney, liver, muscle, and omentum, respectively. The mean mortality rate was 6.7, 20.0, 7.1, and 12.5%; the mean operative time was 10.2, 27.4, 11.2, and 19.8 min; the marginal islet mass was 100, 600, 600, and 200 islet equivalence units and the mean time to reach euglycemia was 3.0, 15.1, 26.6, and 13.9 days. The glucose kinetics of omental pouch islets was the most similar to controls. Thus, a strategic approach is required for deciding on the best transplantation recipient sites after considering donor sources and islet volume. Alternatives can be chosen based on safety or efficacy.

Keyword

Islets of Langerhans; Kidney; Liver; Muscles; Omentum; Transplantation

MeSH Terms

Animals
Blood Glucose/analysis
Diabetes Mellitus, Experimental/chemically induced/mortality
Glucose Tolerance Test
Hyperglycemia/therapy
*Islets of Langerhans Transplantation
Kidney
Liver
Mice
Mice, Inbred C57BL
Muscle, Skeletal
Omentum
*Transplantation, Heterotopic
Blood Glucose

Figure

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  Fig. 1 The change in blood glucose concentration for individual mice in the four transplantation groups. Only the blood glucose concentration of successfully treated mice is plotted. The arrows indicate the excision of islet-bearing grafts and show a prompt increase in blood glucose concentration except for the liver transplantation group. The kidney transplantation group has the shortest time to reach euglycemia after transplantation and lower glucose baseline with strict metabolic control. The muscle transplantation group shows delayed function after transplantation and a higher baseline with frequent events of glucose concentrations >200 mg/dL.

• 

  Fig. 2 Marginal mass of islets for each transplantation site. Each point represents the transplanted islet volume and average blood glucose concentration. The filled circles indicate successful islet transplantation associated with normoglycemia. The empty circles indicate failed islet transplantation associated with hyperglycemia. The marginal masses for the kidney, liver, muscle, and omentum are 100, 600, 600, and 200 islets, respectively. Note that the liver and muscle transplantation groups show a wider range of glucose control ability in relation to the marginal mass, whereas the kidney and omentum transplantation groups show a sharp decline in glucose control ability in relation to the marginal mass.

• 

  Fig. 3 Glucose tolerance test results of the four groups compared with the normal control. The intraperitoneal glucose tolerance test was performed 3 months after transplantation. The solid line indicates the blood glucose response in the normal control. The blood glucose concentration decreases faster in the omentum transplantation group (▲) than in the others. The area under the curve does not differ significantly between the omentum transplantation group and normal controls. Individual curves have been shifted slightly to prevent overlap. The values are expressed as the mean±SEM. The area under the curve was calculated and analyzed using ANOVA. *P<0.05 vs. control group; †P<0.01 vs. the control group; ‡P<0.05 between omentum and muscle groups (▽) kidney, (▼) liver and, (△) muscle. IPGTT, intraperitoneal glucose tolerance test.

• 

  Fig. 4 Dithizone and H&E staining of the four transplantation sites and the histological appearance of an islet graft at 3 months after transplantation. Note the pinkish stained areas of the engrafted islets. Dithizone staining of the section provided instant localization of the islets in the kidney (A), liver (B), muscle (C), and omentum (D). Dithizone staining, original magnification ×50. H&E staining, original magnifications ×50 and ×100.

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