Islet Transplantation under the Kidney Capsule Corrects the Defects in Glycogen Metabolism in Both Liver and Muscle of Streptozocin-Diabetic Rats

Abstract

Insulin-deficient rats are characterized by multiple defects in the pathway of glycogen synthesis and breakdown in both liver and skeletal muscle. The aim of this study was to clarify whether islet transplantation under the kidney capsule, which is associated with delivery of insulin into the peripheral circulation, is able to normalize glycogen metabolism in liver and muscle of streptozotocin-diabetic rats. Three groups of male Lewis rats were studied under fasting condition: controls, untreated diabetics, and islet transplanted diabetics. Glycogen content, glucose-6-phosphate concentration, and glycogen synthase activity were measured in both liver and skeletal muscle. Untreated diabetic rats were characterized by an increase in glycogen content of 178% and a reduction of glucose-6-phosphate level of 50%. Both glycogen and glucose-6-phosphate contents were restored to normal in transplanted diabetic rats. Active glycogen synthase (0.35 ± 0.1 nmol/min/mg) and activity ratio (0.22 ± 0.04) were significantly impaired compared with controls (0.99 ± 0.2 nmol/min/mg and 0.43 ± 0.06, respectively) and were normalized by islet transplantation. In the skeletal muscle, glycogen content was similar in the three groups of animals, whereas muscle glucose-6-phosphate level was reduced by 28% and glycogen synthase was in a less active state in the untreated diabetic rats. Both the glucose-6-phosphate concentration and the kinetic profile of glycogen synthase were normalized by islet transplantation. In conclusion, islet transplantation under the kidney capsule corrects the diabetes-induced abnormalities in glycogen and glucose-6-phosphate content and glycogen synthase activity in both liver and skeletal muscle.

Islet autotransplantation to prevent or minimize diabetes after pancreatectomy

“…It is the only site in humans associated with achieving insulin independence [7]. Other sites have been used, such as the renal capsule [54][55][56][57], spleen [53,58], omentum [59], and peritoneal cavity [60,61], but have rarely been associated with function of islet autografts in humans [62,63]. Presumably, islets survive by nutrient diffusion and have reduced functional capacity until neovascularization occurs [64,65].…”

Vascularized tissue‐engineered chambers promote survival and function of transplanted islets and improve glycemic control

“…In this study, we have shown that islets seeded into vascularized chambers reduce hyperglycemia in STZ‐induced diabetic mice just as effectively as islets injected under the renal capsule, the “benchmark” procedure (6).…”

Pancreatic Islet Cell Transplantation: A Treatment Strategy for Type I Diabetes Mellitus

“…Anatomic Sites for Islet Cell Transplantation Different anatomic locations were tried for the engrafting of the islet cells. [35][36][37] The liver is currently the preferred target organ for islet cell transplantation in humans. The portal vein is the preferred site of infusion, 36 given the relative ease of access and the high venous flow with a double circulation system (arterial and portal venous) of the liver, allowing engraftment more likely without infarction.…”

“…The kidneys are used as a site of infusion for islet cells primarily in animal experimental islet cell transplantation. 35 Islets are injected under the kidney capsule, a well-vascularized area of the organ. This site is a less attractive one in humans because the kidney is less accessible for surgery or interventional radiology.…”