A 72-year-old man who had suffered several episodes of syncope was diagnosed as having hyperinsulinemic hypoglycemia. Although imaging studies and percutaneous transhepatic portal venous sampling did not reveal the existence of any tumors in the pancreas, distal pancreatectomy was performed because the possibility of a small pancreatic endocrine tumor could not be completely rejected. External examination of the surgically removed pancreas did not reveal any tumors. Microscopically, the pancreas exhibited diffuse islet cell hyperplasia without nesidioblastosis. The patient remains euglycemic and has tolerated 24-hour fasting without any medication for a period of 10 months after the operation.
Aged ; Case Report ; Human ; Hyperinsulinemia/etiology* ; Hyperplasia ; Hypoglycemia/etiology* ; Islets of Langerhans/surgery ; Islets of Langerhans/pathology* ; Male ; Pancreatectomy/methods ; Treatment Outcome

To explore the possible new mechanism of acupuncture in the treatment of diabetes mellitus type 2 (T2DM) based on the islet inflammatory response. Islet macrophages, pancreatic adipose cells and islet β cells all participate in the pathogenesis of T2DM, and the three could form a network interaction. Acupuncture could regulate the functional phenotype of islet macrophages, improve the ectopic deposition of pancreatic adipose and repair the function of islet β cells, and play a unique advantage of overall regulation. It is suggested that acupuncture can be a potential treatment strategy for T2DM.
Acupuncture Therapy ; Diabetes Mellitus, Type 2/therapy* ; Humans ; Insulin-Secreting Cells/pathology* ; Islets of Langerhans/pathology* ; Macrophages

OBJECTIVES: Heparin is mainly used as an anticoagulant in clinic, and it also has a certain anti-inflammatory effect. At present, after portal vein islet transplantation in diabetic patients, heparin is mainly infused through the peripheral veins of the limbs to achieve the purpose of anticoagulation and protection of the graft, rather than through the portal vein. In this study, animal experiments were conducted to investigate the effect of heparin infusion via the portal vein and marginal ear vein on the instant blood-mediated inflammatory reaction (IBMIR) after portal vein islet transplantation, which is the choice of anticoagulation methods for clinical islet transplantation to provide a basis for decision-making. METHODS: A total of 50 neonatal pigs (Xeno-1 type, 3-5 days) were selected. Islets were isolated and purified from the pancreas of neonatal pigs. Ten non-diabetic Landrace pigs (1.5-2.0 months) served as recipients, and 12 000 IEQ/kg neonatal porcine islets were transplanted into the liver through the portal vein. All recipients received bolus injection of 50 U/kg of heparin 10 minutes before transplantation. After the bolus injection of heparin, the experimental group received heparin via the portal vein [10 U/(kg·h), 5 recipients], and the control group received heparin via the marginal ear vein [10 U/(kg·h), 5 recipients]. The superior vena cava blood was collected from the 2 groups pre-operation at 1, 3, 24 h post-operation of the transplantation. The portal vein blood was collected from the experimental group at 1 and 3 h after the transplantation as well. The levels of complement C3a, C5a, thrombin-antithrombin complex (TAT), β-thromboglobulin (β-TG), and D-dimer as well as activated partial thromboplastin time (APTT) in superior vena cava blood from 1 and 3 h post-transplantation were detected in the 2 groups, and the levels of anti-Xa and anti-IIa in the portal vein and superior vena cava blood from 1 and 3 h post-transplantation in the experimental group were detected. Twenty four hours after the transplantation, the liver tissues in the 2 groups were collected for pathological examination to observe the inflammatory cell infiltration and peripheral thrombosis around the islets graft in liver. RESULTS: Before transplantation, there was no statistically significant difference in C3a, C5a, TAT, β-TG, D-dimer levels and APTT between the 2 groups (all P>0.05). At 1 and 3 h after transplantation, the C3a, TAT, and D-dimer levels in the experimental group were significant decreased than those in the control groups (all P<0.05), and at 3 h after transplantation the C5a was significant decreased than that in the control group (P<0.05). At 1 and 3 h after transplantation, the anti-Xa and anti-IIa levels in the portal vein blood were significantly increased than those in the superior vena cava blood in the experimental group (all P<0.05). Pathological results showed the presence of islet cell clusters in the liver blood vessels. The thrombus formation and neutrophil infiltration around islet graft was not obvious in the experimental group, while massive thrombus formation and neutrophil infiltration in the control group. CONCLUSIONS Compared with marginal ear vein infusion of heparin, the direct infusion of heparin in the portal vein has a certain inhibitory effect on complement system, coagulation system activation and inflammatory cell infiltration in portal vein islet transplantation, which may attenuate the occurrence of IBMIR.
Animals ; Anticoagulants/therapeutic use* ; Heparin/therapeutic use* ; Humans ; Islets of Langerhans/pathology* ; Islets of Langerhans Transplantation/physiology* ; Portal Vein ; Swine ; Vena Cava, Superior

A case of nonfunctioning pancreatic islet cell tumor is described. A 34 years old female patient had intermittent epigastric pain and nausea for 6 months and she had nothing suggestive of neuroendocrine symtoms. Physcial examination showed an epigastric mass which wae deepseated, nontender, and well-demarcated. The routine upper endoscopic evatuation was negative. Abdominal ultrasonography and computed tomography showed a well-defined round solid mass with multifocal necrosis but did not revealed the origin of the lesion. Endoscopic retrograde pancreatography showed upward and rightward displacement of the proximal body portion of main pancreatic duct with nonvisualization of the secondary branches of pancreatic duct, suggesting that the mass originated from the pancreas. Resection of the mass with partial pancreatectomy and Roux-en-Y pancreaticojejunostomy was perfomed and the pathology was coafirmed as nonfunctioning pancreatic islet cell tumor containing somatostatin by immunohistochemical technique.
Adenoma, Islet Cell ; Adult ; Female ; Humans ; Immunohistochemistry ; Islets of Langerhans* ; Nausea ; Necrosis ; Pancreas ; Pancreatectomy ; Pancreatic Ducts ; Pancreaticojejunostomy ; Pathology ; Somatostatin ; Ultrasonography

BACKGROUND: Minor histocompatibility HY antigen, as a transplantation antigen, has been known to cause graft rejection in MHC (major histocompatibility complex) matched donor-recipient. The aim of our study is to investigate the role of male antigen (HY) disparity on MHC matched pancreatic islet transplantation and to examine the mechanism of the immune reaction. METHODS: Pancreatic islets were isolated and purified by collagen digestion followed by Ficoll gradient. The isolated islets of male C57BL6/J were transplanted underneath the kidney capsule of syngeneic female mice rendered diabetic with streptozotocine. Blood glucose was monitored for the rejection of engrafted islets. After certain period of time, tail to flank skin transplantation was performed either on mouse transplanted with HY mismatched islets or on sham treated mouse. The rejection was monitored by scoring gross pathology of the engrafted skin. RESULTS: HY mismatched islets survived more than 300 days in 14 out of 15 mice. The acceptance of second party graft (male B6 islets) and the rejection of third party graft (male BALB/c islets) in these mice suggested the tolerance to islets with HY disparity. B6 Skin with HY disparity was rejected on day 25 +/- 7. However, HY mismatched skin transplanted on the mice tolerated to HY mismatched islets survived more than 240 days. Tetramer staining in these mice indicated the CTL recognizing MHC Db/Uty was not deleted or anergized. CONCLUSION: The islet transplantation across HY disparity induced tolerance to HY antigen in C57BL6 mouse, which in turn induced tolerance to HY mismatched skin, which otherwise would be rejected within 25 days. The MHC tetramer staining suggested the underlying mechanisms would not be clonal deletion or anergy.
Animals ; Blood Glucose ; Clonal Deletion ; Collagen ; Digestion ; Female ; Ficoll ; Graft Rejection ; H-Y Antigen ; Histocompatibility ; Humans ; Immune Tolerance* ; Islets of Langerhans ; Islets of Langerhans Transplantation* ; Kidney ; Male ; Mice ; Pathology ; Skin ; Skin Transplantation ; Streptozocin ; Tail ; Transplants

OBJECTIVETo explore the synergistic protective effect of co-transplanted testicular cells expressing FasL and CsA on survival of islet allografts.

METHODSThe allogeneic islets and testicular cells were co-transplanted into the renal subcapsular space of the diabetic recipients with or without CsA after operation. Allografts survival period and the testicular cells or islets function were analyzed.

RESULTSThe mean survival period of control group was 4.6 +/- 1.1 days. When CsA was administered after transplantation, the mean survival period of islet allografts, (21.8 +/- 4.7) days, was significantly longer than that of control group (P < 0.01). When islets were co-transplanted together with 1 x 10(7) testicular cells (group A), a significant prolongation of graft survival was found (more than 57.5 +/- 4.0 days; P < 0.01 vs. control). But if 1 x 10(7) testicular cells expressing FasL were cultured with FasL-mAb for 30 minutes before co-transplantation (group B), the mean survival period of islet allografts (5.8 +/- 2.6 days), was similar to that in control group, but significantly shorter than that in group A (P < 0.01). When islets and 1 x 10(5) testicular cells were co-transplanted separately into the bilateral renal subcapsular space with CsA (group C), the survival of islet allografts was significantly prolonged in comparison with control group (more than 55.0 +/- 6.5 days; P < 0.01 vs. control), and similar to islets co-transplanted together with 1 x 10(7) testicular cells (group A). When islets were co-transplanted separately with 1 x 10(6) testicular cells without CsA (group D), the mean survival period (11.5 +/- 3.1 days) was shorter than that in group C, but prolonged in comparison to control group (P < 0.05).

CONCLUSIONThe co-transplanted testicular cells expressing FasL with administering CsA post-transplantation can jointly inhibit immune rejection of islet allografts by different mechanism and play a systemic and synergistic protective role to islet allografts.

Animals ; Cyclosporine ; therapeutic use ; Fas Ligand Protein ; Graft Survival ; Immunohistochemistry ; Insulin ; blood ; Islets of Langerhans ; pathology ; ultrastructure ; Islets of Langerhans Transplantation ; Male ; Membrane Glycoproteins ; analysis ; genetics ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Sertoli Cells ; metabolism ; transplantation ; Transplantation, Homologous

OBJECTIVETo explore the effect of Jiangtang Xiaozhi capsule (JXC) on morphological changes of islets and liver at rat model of type 2 diabetic mellitus and provide the experimental basis for the clinical therapy of type 2 diabetic mellitus.

METHODWister rats were fed on a diet enriched in fat and glucose to induce insulin resistan, the rats were injected intrapertoneally with a low-dose streptozotocin (STZ) twice (25 mg x kg(-1)) to induce hyperglycemia, so the successful rat model of type 2 diabetes were established. The experimental rats were divided into model group, high dose JXC group, middle dose JXC group, low dose JXC group, Erjiashuanggua group, Jinqijiangtang group and normal control group. After all the treatment groups received their own medicine for two months, all the rats were sacrificed and morphological examination on their islets and livers were performed.

RESULTFatty liver in various degrees was seen in the model group and all the treatment groups, but the liver steatosis in middle and low dose JXC groups was significantly milder than that in model group (P < 0.05). Islets in the high dose JXC group were significantly more than that in the model group (P < 0.05).

CONCLUSIONJXC can improve significantly the pathological change in islets and liver steatosis at rat model of type 2 diabetic mellitus.

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Islets of Langerhans ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Male ; Microscopy ; Rats ; Rats, Wistar

This study was performed to observe the changes of glucose-related hormones and the morphological change including ultrastructure of the pancreatic islets in the male Otsuka Long-Evans Tokushima Fatty rat. Area under the curve (AUC) of glucose at the 30th (709 +/- 73 mg.h/dL) and at the 40th week (746 +/- 87 mg.h/ dL) of age were significantly higher than that at the 10th week (360 +/- 25 mg.h/ dL). AUC of insulin of the 10th week was 2.4 +/- 0.9 ng.h/mL, increased gradually to 10.8 +/- 8.3 ng.h/mL at the 30th week, and decreased to 1.8 +/- 1.2 ng.h/mL at the 40th week. The size of islet was increased at 20th week of age and the distribution of peripheral alpha cells and central beta cells at the 10th and 20th weeks was changed to a mixed pattern at the 40th week. On electron microscopic examination, beta cells at the 20th week showed many immature secretory granules, increased mitochondria, and hypertrophied Golgi complex and endoplasmic reticulum. At the 40th week, beta cell contained scanty intracellular organelles and secretory granules and apoptosis of acinar cell was observed. In conclusion, as diabetes progressed, increased secretion of insulin was accompanied by increases in size of islets and number of beta-cells in male OLETF rats showing obese type 2 diabetes. However, these compensatory changes could not overcome the requirement of insulin according to the continuous hyperglycemia after development of diabetes.
Animals ; Body Weight ; Diabetes Mellitus, Type 2/*metabolism/pathology ; Disease Models, Animal ; Glucagon/*metabolism ; Insulin/*metabolism ; Islets of Langerhans/*metabolism/pathology/ultrastructure ; Male ; Rats ; Rats, Inbred OLETF

OBJECTIVETo investigate the effects of various HIV protease inhibitors on the function of pancreatic beta-cells.

METHODSRat insulinoma INS-1 cells were incubated with different concentrations of ritonavir or amprenavir for 48 h and stimulated with 20 mmol/L D-glucose for 30 min. The rate of insulin release was measured in the supernatant by ELISA, normalized to cellular DNA contents. Cells were counted with trypan blue and MTT test were determined to evaluate the effect of protease inhibitors on cell viability.

RESULTRitonavir treatment significantly decreased baseline insulin release and glucose-stimulated insulin release in a dose-dependent manner (r=-0.861, -0.839, both P<0.01). For 10 micromol/L of ritonavir, the decrease rate of baseline insulin secretion and glucose-stimulated insulin secretion was 46% and 47%, respectively. Amprenavir had no effect on the rate of insulin release.

CONCLUSIONVarious HIV protease inhibitors present different effect on the insulin release of pancreatic beta-cells.

Animals ; Carbamates ; pharmacology ; HIV Protease Inhibitors ; pharmacology ; Insulin ; secretion ; Insulinoma ; metabolism ; pathology ; Islets of Langerhans ; metabolism ; Pancreatic Neoplasms ; metabolism ; pathology ; Rats ; Ritonavir ; pharmacology ; Sulfonamides ; pharmacology

OBJECTIVETo investigate the effect of Cordyceps sinensis (CS) on pancreatic islet B cells of experimental hepatic fibrogenesis rats.

METHODSRats were randomly allocated into three groups: normal group, model group and CS group. The rats in the latter two groups were administered with CCl(4) solution to induce liver fibrosis, the CS group was also treated with CS 10 days after the beginning of CCl(4) administration. Rats in normal group were sacrificed at the beginning of the experiment, while the rats in the other two groups were sacrificed randomly at the end of the third and sixth weeks. The rats' islets were isolated and cultured in vitro, then the basal insulin level of the islets and the serum level of insulin were determined by radioimmunological assay.

RESULTSIt seemed no change that the levels of serum insulin and basal insulin between the model group and the normal group at the third week. But at the sixth week, both insulin levels in the model group were higher than those in the normal group (52.6 mU/L2.5 mU/L vs 23.7 mU/L 2.3 mU/L, q=13.01, p<0.05; 52.94muU/ml 13.12muU/ml vs 35.16muU/ml 5.64muU/ml, q=10.06, p<0.01). No significant change could be seen in the serum levels of insulin between the CS group and the model group at the third and sixth weeks. But the basal insulin levels in the CS group were apparently higher than those in the model group at the third and sixth weeks (156.63muU/ml 6.57muU/ml vs 39.64muU/ml 3.95muU/ml, q=66.94, p<0.001; 140.44muU/ml 38.53muU/ml vs 52.94muU/ml 13.12muU/ml, q=12.98, p<0.01).

CONCLUSIONCordyceps sinensis can increase the basal insulin level of the islets in CCl(4)-induced liver fibrosis rats.

Animals ; Carbon Tetrachloride ; toxicity ; Cordyceps ; Female ; Insulin ; blood ; secretion ; Islets of Langerhans ; physiopathology ; Liver ; pathology ; Liver Cirrhosis, Experimental ; pathology ; physiopathology ; therapy ; Male ; Rats ; Rats, Wistar