As a member of the apolipoprotein C (ApoC) family with a relatively high content, ApoC3 plays a major role in the regulation of triglyceride metabolism, and plays an important role in the occurrence and development of cardiovascular diseases, glucose and lipid metabolism disorders. Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of a large amount of fat in the liver in the absence of a history of chronic alcohol consumption or other damage to the liver. A large number of previous studies have shown that there is a correlation between the gene polymorphism and high expression of ApoC3 and NAFLD. In the context of hypertriglyceridemia (HTG), this article reviews the relationship between ApoC3 and NAFLD, glucose and lipid metabolism, and islet β cell function, showing that ApoC3 can not only inhibit lipoprotein lipase (LPL) and hepatic lipase (HL) activity, delay the decomposition of triglyceride in plasma to maintain the body's energy metabolism during fasting, but also be significantly increased under insulin resistance, prompting the liver to secrete a large amount of very low-density lipoprotein (VLDL) to induce HTG. Therefore, targeting and inhibiting ApoC3 might become a new approach to treat HTG. Increasing evidence suggests that ApoC3 does not appear to be an independent "contributor" to NAFLD. Similarly, our previous studies have shown that ApoC3 is not an independent factor triggering islet β cell dysfunction in ApoC3 transgenic mice, but in a state of excess nutrition, HTG triggered by ApoC3 high expression may exacerbate the effects of hyperglycemia and insulin resistance on islet β cell function, and the underlying mechanism remains to be further discussed.
Apolipoprotein C-III/genetics* ; Non-alcoholic Fatty Liver Disease/pathology* ; Glucose/metabolism* ; Lipid Metabolism ; Humans ; Animals ; Hypertriglyceridemia/metabolism* ; Islets of Langerhans/metabolism*

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

Intraportal transplantation of islets is no longer considered to be an ideal procedure and finding the extrahepatic alternative site is becoming a subject of high priority. Herein, in this study, we would introduce our initial outcomes of using gastric submucosa (GS) and liver as sites of islet autotransplantation in pancreatectomized diabetic Beagles. Total pancreatectomy was performed in Beagles and then their own islets extracted from the excised pancreas were transplanted into GS (GS group, n=8) or intrahepatic via portal vein (PV group, n=5). Forty-eight hours post transplantation, graft containing tissue harvested from the recipients revealed the presence of insulin-positive cells. All recipients in GS group achieved euglycemia within 1 day, but returned to a diabetic state at 6 to 8 days post-transplantation (mean survival time, 7.16±0.69 days). However, all of the animals kept normoglycemic until 85 to 155 days post-transplantation in PV group (mean survival time, 120±28.58 days; P<0.01 vs. GS group). The results of intravenous glucose tolerance test (IVGTT) confirmed that the marked improvement in glycometabolism was obtained in intrahepatic islet autotransplantation. Thus, our findings indicate that the liver is still superior to the GS as the site of islet transplantation, at least in our islet autotransplant model in pancreatectomized diabetic Beagles.
Animals ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; therapy ; Dogs ; Gastric Mucosa ; metabolism ; transplantation ; Glucose ; metabolism ; Glucose Tolerance Test ; Graft Survival ; Humans ; Insulin ; metabolism ; Islets of Langerhans Transplantation ; Liver ; pathology ; Liver Transplantation ; Transplantation, Autologous

The Goto-Kakizaki (GK) rat is a spontaneous type 2 diabetic animal model, which is characterized by a progressive loss of beta islet cells with fibrosis. In the present study, the hypoglycemic effect of asiatic acid (AA) in GK rats was examined. GK rats receiving AA at a daily dose of 25 mg·kg(-1) for four weeks showed a significant reduction in blood glucose levels. Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose (CMC-Na) solution for the same periods and used as control. Compared to the normal Wistar rats, GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level (P < 0.01) and insulin level (P < 0.05). Furthermore, the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats. Fibronectin, a key protein related to islet fibrosis, was over-expressed in GK rats, which was reversed significantly by AA treatment (P < 0.05). These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes, which may play a role in the prevention of islets dysfunction.
Animals ; Blood Glucose ; metabolism ; Centella ; chemistry ; Diabetes Mellitus, Type 2 ; drug therapy ; pathology ; Disease Models, Animal ; Fibronectins ; metabolism ; Fibrosis ; Glucose Tolerance Test ; Hyperglycemia ; drug therapy ; pathology ; Insulin ; blood ; Insulin Resistance ; Islets of Langerhans ; drug effects ; pathology ; Male ; Pancreatic Diseases ; metabolism ; pathology ; prevention & control ; Pentacyclic Triterpenes ; pharmacology ; therapeutic use ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Inbred Strains

Nesidioblastosis is a term used to describe pathologic overgrowth of pancreatic islet cells. It also means maldistribution of islet cells within the ductules of exocrine pancreas. Generally, nesidioblastosis occurs in beta-cell and causes neonatal hyperinsulinemic hypoglycemia or adult noninsulinoma pancreatogenous hypoglycemia syndrome. Alpha-cell nesidioblastosis and hyperplasia is an extremely rare disorder. It often accompanies glucagon-producing marco- and mircoadenoma without typical glucagonoma syndrome. A 35-year-old female was referred to our hospital with recurrent acute pancreatitis. On radiologic studies, 1.5 cm sized mass was noted in pancreas tail. Cytological evaluation with EUS-fine-needle aspiration suggested serous cystadenoma. She received distal pancreatectomy. The histologic examination revealed a 1.7 cm sized neuroendocrine tumor positive for immunohistochemical staining with glucagon antibody. Multiple glucagon-producing micro endocrine cell tumors were scattered next to the main tumor. Additionally, diffuse hyperplasia of pancreatic islets and ectopic proliferation of islet cells in centroacinar area, findings compatible to nesidioblastosis, were seen. These hyperplasia and almost all nesidioblastic cells were positive for glucagon immunochemistry. Even though serum glucagon level still remained higher than the reference value, she has been followed-up without any evidence of recurrence or hormone related symptoms. Herein, we report a case of alpha-cell nesidioblastosis and hyperplasia combined with glucagon-producing neuroendocrine tumor with literature review.
Adult ; Chromogranin A/blood ; Female ; Glucagon/*metabolism ; Glucagon-Secreting Cells/metabolism ; Humans ; Hyperplasia/complications/*diagnosis ; Islets of Langerhans/metabolism/ultrasonography ; Nesidioblastosis/complications/*diagnosis ; Neuroendocrine Tumors/complications/*diagnosis/pathology ; Pancreas/*pathology ; Tomography, X-Ray Computed

OBJECTIVETo analyze the biochemical and pathological changes in mice with type 2 diabetes mellitus (T2DM) induced by high-fat diet combined with low-dose streptozotocin (STZ) injections.

METHODSC57BL/6J mice were divided randomly into normal control group (NC group), high-fat diet group (HC group) and high-fat diet plus STZ group (HC+STZ group). The mice were fed on normal chow or a high-fat diet for 1 month before two introperitoneal injections of STZ (40 mg/kg) or citrate buffer with an interval of 24 h as appropriate. Fasting blood glucose (FBG) was detected every week for 4 weeks, and oral glucose tolerance test (OGTT) was performed one month after the injections, after which the biochemical profiles, islet and liver were evaluated by immunohistochemical and pathological analysis.

RESULTSIn HC+STZ group, FBG was above the cutoff value (13.89 mmol/L) in 75% of the mice at 1 week after STZ injections and in all the mice at two weeks except for the death of 1 mouse, with a success rate of modeling of 91.3%. FBG in HC group, though slightly higher than that in NC group, remained normal (6.8 mmol/L). The body weight in HC+STZ and HC groups was significantly higher than that in NC group after feeding but without obvious increases after the injections (P<0.01). Blood glucose in HC+STZ group at 0.5 to 2 h after OGTT and the area under curve (AUC) were higher than those in NC and HC groups (P<0.01); the AUC in HC group was a also higher than that in NC group (P<0.05). Plasma creatinine was significantly higher in HC+STZ group than in NC (P<0.01) and HC (P<0.05) groups. Insulin secretion by the islets decreased obviously in HC+STZ and HC group. The mice in HC+STZ group showed atrophy, fibrosis, and vacuolization in the islets with mild fatty liver but no visible renal pathologies.

CONCLUSIONHigh-fat diet and low-dose STZ injections can induce T2DM in mice with very similar biochemical and pathological changes to human T2DM and with such complications as fatty liver.

Animals ; Blood Glucose ; Body Weight ; Diabetes Mellitus, Type 2 ; physiopathology ; Diet, High-Fat ; Fatty Liver ; physiopathology ; Glucose Tolerance Test ; Insulin ; Insulin Resistance ; Islets of Langerhans ; pathology ; Kidney ; pathology ; Mice ; Mice, Inbred C57BL ; Streptozocin

OBJECTIVETo study the effect of pretreatment with apoptotic donor spleen cells on spleen lymphocyte function of recipient rats undergoing islet transplantation to explore new approaches to prolong islet graft survival.

METHODSApoptotic spleen cells from donor rats were obtained by exposure to γ-ray irradiation from (60)Co. Diabetic SD rat models were randomly divided into 4 groups to receive tail vein injections with saline (group A), normal cells (group B), apoptotic donor cells (group C), or necrotic donor cells (group D). One week later, orthotopic transplantation of islets under the renal capsule was performed. Before and at 1 and 2 weeks after islet transplantation, the recipient rats were examined for proliferative activity of spleen lymphocytes with CFSE cell staining and for IL-2 and IL-10 expressions in the cells using ELISA.

RESULTSPretreatment with donor apoptotic cells significantly suppressed the proliferative activity of recipient spleen lymphocytes before and at 1 and 2 weeks after islet transplantation as compared with the other three groups (P<0.05). The level of IL-2 was significantly decreased while IL-10 increased in apoptotic donor cell pretreatment group compared with those in the other 3 groups at each time point of observation.

CONCLUSIONThe effect of pretreatment with apoptotic donor cells on recipient spleen lymphocytes suggest an important role of apoptotic donor spleen cells in immune tolerance of grafts.

Animals ; Apoptosis ; immunology ; Cell Proliferation ; Cobalt Radioisotopes ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; surgery ; Gamma Rays ; Graft Survival ; Immune Tolerance ; Interleukin-10 ; metabolism ; Interleukin-2 ; metabolism ; Islets of Langerhans Transplantation ; Lymphocyte Transfusion ; Lymphocytes ; metabolism ; pathology ; radiation effects ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Spleen ; cytology ; metabolism ; radiation effects

Transplantation of islet cells into diabetic patients is a promising therapy, provided that the islet cells are able to evade host immune rejection. With improved islet viability, this strategy may effectively reverse diabetes. We applied 2% calcium alginate to generate small and large capsules to encapsulate porcine neonatal pancreatic cell clusters (NPCCs) using an air-driven encapsulator. After encapsulation, the viability was assessed at 1, 4, 7, 14 and 28 days and secretion of functional insulin in response to glucose stimulation were tested at days 14 and 28. Selective permeability of the small alginate capsules was confirmed using various sizes of isothiocyanate-labeled dextran (FITC-dextran). Encapsulation of NPCCs was performed without islet protrusion in the small and large capsules. The viability of NPCCs in all experimental groups was greater than 90% at day 1 and then gradually decreased after day 7. The NPCCs encapsulated in large capsules showed significantly lower viability (79.50 +/- 2.88%) than that of naive NPCCs and NPCCs in small capsule (86.83 +/- 2.32%, 87.67 +/- 2.07%, respectively) at day 7. The viability of naive NPCCs decreased rapidly at day 14 (75.67 +/- 1.75%), whereas the NPCCs encapsulated in small capsules maintained (82.0 +/- 2.19%). After 14 and 28 days NPCCs' function in small capsules (2.67 +/- 0.09 and 2.13 +/- 0.09) was conserved better compared to that of naive NPCCs (2.04 +/- 0.25 and 1.53 +/- 0.32, respectively) and NPCCs in large capsules (2.04 +/- 0.34 and 1.13 +/- 0.10, respectively), as assessed by a stimulation index. The small capsules also demonstrated selective permeability. With this encapsulation technique, small capsules improved the viability and insulin secretion of NPCCs without islet protrusion.
Alginates/chemistry/metabolism ; Animals ; Animals, Newborn ; Capsules/chemistry ; Cell Survival ; Diabetes Mellitus/pathology/*therapy ; Disease Models, Animal ; Glucuronic Acid/chemistry/metabolism ; Graft Rejection/etiology/*prevention & control ; Hexuronic Acids/chemistry/metabolism ; Humans ; Insulin/secretion ; Islets of Langerhans/*metabolism/pathology ; Islets of Langerhans Transplantation/*methods ; Postoperative Complications/etiology/*prevention & control ; *Swine

A 39-year-old female patient presented to our hospital with epigastric pain lasting for two months. Laboratory results showed impaired glucose tolerance. Ultrasonography of the patient showed a hypoechoic, diffusely enlarged pancreas. CT revealed a large pancreas, with multiple calcifications. On MRI, a diffusely enlarged pancreas was seen hypointense on both T1- and T2-weighted images with heterogeneous enhancement after gadolinium administration. A biopsy of the pancreas revealed primary amyloidosis of islet cells. Decreased signal on T1-weighted images without inflammation findings on CT and MRI were clues for the diagnosis.
Adult ; Amyloidosis/*diagnosis ; Contrast Media/diagnostic use ; Diagnosis, Differential ; *Diagnostic Imaging ; Female ; Glucose Tolerance Test ; Humans ; Islets of Langerhans/*pathology ; Pancreatic Diseases/*diagnosis