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<p><b>BACKGROUND</b>The induced expression of heme oxygenase-1 (HO-1) in donor islets improves allograft survival. Cobalt protoporphyrin (CoPP) could significantly enhance the expression of HO-1 mRNA and protein in rat islet safely. Our work was to study how to protect pancreatic islet xenograft by CoPP-induction.</p><p><b>METHODS</b>Islet xenografts treated with CoPP-induction and CoPP + Zinc protoporphyrin (ZnPP) in vitro and in vivo were randomly transplanted into murine subrenal capsule; then the graft survival time was compared by blood glucose level and pathological examination and meanwhile the interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10) and IL-1β level in serum and their mRNA and HO-1 mRNA and protein expression were examined.</p><p><b>RESULTS</b>Islets with CoPP-induction under low- and high-glucose stimulation exhibited much higher insulin secretion compared with other three groups. CoPP-induction could increase higher expression of HO-1 (mRNA: 3.33- and 76.09-fold in vitro and in vivo; protein: 2.85- and 58.72-fold). The normoglycemia time in induction groups ((14.63 ± 1.19) and (16.88 ± 1.64) days) was significantly longer. The pathological examination showed less lymphocyte infiltration in induction groups. The IL-10 level and its mRNA in induction groups were significantly higher.</p><p><b>CONCLUSIONS</b>The HO-1 induced by CoPP would significantly improve function, prolong normoglycemia time and reduce lymphocyte infiltration. Meanwhile CoPP-induction in vivo had more beneficial effects than in vitro. Its mechanism could be related to immune-modulation of IL-10.</p>
Subject(s)
Animals , Male , Mice , Rats , Blotting, Western , Graft Survival , Heme Oxygenase-1 , Genetics , Metabolism , Interleukin-10 , Blood , Islets of Langerhans , Metabolism , Islets of Langerhans Transplantation , Mice, Inbred BALB C , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Transplantation, HeterologousABSTRACT
<p><b>OBJECTIVE</b>To study the protective effect of islet xenograft and its possible mechanism of high expression of heme oxygenase-1 (HO-1) in donor pancreas islet induced by cobalt protoporphyrin (CoPP).</p><p><b>METHODS</b>Male SD rats and C57BL/6 mouse were used as donors and recipients respectively. Donors were divided into 3 groups according to different pretreatment 24 hours before donation: control group (injected intraperitoneally with NaCl), induce group [injected intraperitoneally with cobalt-protoporphyrin (CoPP)], block group (injected intraperitoneally with CoPP and zinc protoporphyrin simultaneously). A modified approach was used for islet isolation.Recipients were rendered diabetic by intraperitoneal injection of streptozotocin. Islets were transplanted into mouse subrenal capsule. Postoperative mouse glycemia were monitored daily and normoglycemia time was compared among each group. The receptor mouse serum IL-10 was detected by ELISA approach, and real-time PCR was used to check the expression of IL-10 mRNA in islet graft tissues. The graft tissues were observed for the lymphocyte infiltration after HE staining.</p><p><b>RESULTS</b>Diabetes mice accepted islets untreated, induced or blocked maintained the euglycemia for (9.3 +/- 1.4), (16.3 +/- 1.5) and (9.7 +/- 1.0) d respectively. The xeno-islets presented HO-1 over-expression survived much longer than that absent (P < 0.05), it was no significance between control group and block group (P > 0.05). The mouse islet serum IL-10 content after induction was (73.0 +/- 9.7) pg/ml, significantly higher than (30.6 +/- 3.9) pg/ml of the untreated group and (32.1 +/- 5.9) pg/ml of the blocked group (P < 0.05), there was no difference between control group and block group (P > 0.05). Moreover, the IL-10 mRNA expression up-regulated statistic significantly in HO-1 induced islet xeno-graft. Pathological examination showed that the graft lymphocyte infiltration of the induced group was obviously less serious than the other two groups.</p><p><b>CONCLUSIONS</b>The higher expression of HO-1 induced by CoPP in vivo would significantly prolong graft survival time and its mechanism could be related to immune modulation of IL-10.</p>
Subject(s)
Animals , Male , Mice , Rats , Diabetes Mellitus, Experimental , Metabolism , Pathology , General Surgery , Graft Survival , Heme Oxygenase-1 , Metabolism , Interleukin-10 , Metabolism , Islets of Langerhans , Metabolism , Pathology , Mice, Inbred C57BL , Pancreas Transplantation , Protoporphyrins , Pharmacology , Rats, Sprague-Dawley , Subrenal Capsule Assay , Transplantation, HeterologousABSTRACT
Objective To discuss the optimal clinical diagnosis and treatment of ectopic ACTH syndrome with occult tumors. Methods Clinical features, imaging examinations and treatment of 17 patients with ectopic ACTH syndrome were described and compared. Results All patients illustrated the typical clinical features of Cushing’s syndrome. They had hypokalemic alkalosis, elevated serum cortisol and plasma ACTH levels. In the high-dose dexamethasone suppression tests, most patients failed to suppress serum cortisol and 24-hour urinary cortisol. CT and MRI are useful imaging modalities to localize the ACTH-secreting tumor in patients with ectopic ACTH syndrome. The patients with overt ACTH-secreting tumors had surgical curative resection soon after diagnosis. Among patients with occult ACTH-secreting tumors, three underwent subtotal bilateral adrenalectomy, two underwent right adrenalectomy, four received inhibitor of steroidogenesis aminoglutethimide. Their hypercortisolism was controlled. Conclusion Surgical curative resection is the optimal treatment of ectopic ACTH syndrome with overt ACTH-secreting tumor. Bilateral adrenalectomy, right adrenal ectomy or chemotherapy to control hypercortisolism is an available treatment of ectopic ACTH syndrome with occult ACTH-secreting tumors.
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Objective To observe the possible association of serum adiponectin level with testosterone level in patients with isolated hypogonadotropic hypogonadism(IHH).Methods The diagnosis of IHH was made,based on clinical presentations,laboratory examinations of hormones and GnRH stimulation test.Serum adiponeetin and testosterone levels were measured in 23 IHH patients and 15 normal men.Results After matched for weight,blood pressure and waist-to-hip ratio,serum testosterone level in IHH group was significantly lower than that in control group [(0.23?0.18 vs 4.20?1.90)?g/L,P
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Objective To investigate the effect of calcium antagonist verapamil on the function of rat?- cells and tolbutamide (D860)-induced insulin release.Methods Insulin released from isolated islets were measured in control,verapamil,D860,and verapamil+D860 groups.Furthermore,intravenous glucose tolerance test (IVGTT) was conducted in acute experiments treated with verapamil and D860 respectively to assess?-cell function in rats with the same allocation as in vitro.Another IVGTT was performed in the end of 4 weeks' treatment.The insulin contents in pancreas were assayed and pancreas islets morphology were observed with immunohistochemistry.Results Verapamil could inhibit insulin release from isolated islets.Verapamil group was [(1.244?0.082)ng?ml~(-1)?islet~(-1)]and control group (2.623?0.226) ng?ml~(-1)?islet~(-1)(P0.05).Also,similar results were obtained in normal rats during acute experiments and verapamil reduce the hypoglycemic effect promoted by D860. However,above results were not observed in the end of 4 weeks experiments,and no difference for insulin content and morphological change in islets was found among four groups.Conclusion Treatment of verapamil chronically does not impair islet function and interfere with the hypoglycemic effect of D860 in rats .