To investigate whether BCG, lymphtoxin (LT) or bee venom (BV) can prevent insulitis and development of diabetes in non-obese diabetic (NOD) mice, we measured the degree of insulitis and incidence of diabetes in 24 ICR and 96 female NOD mice. NOD mice were randomly assigned to control, BCG-, LT-, and BV-treated groups. The BCG was given once at 6 weeks of age, and LT was given in 3 weekly doses from the age of 4 to 10 weeks. The BV was injected in 2 weekly doses from the age of 4 to 10 weeks. Diabetes started in control group at 18 weeks of age, in BCG group at 24 weeks of age, and in LT- or BV-treated group at 23 weeks of age. Cumulative incidences of diabetes at 25 weeks of age in control, BCG-, LT-, and BV-treated NOD mice are 58, 17, 25, and 21%, respectively. Incidence and severity of insulitis were reduced by BCG, LT and BV treatment. In conclusion, these results suggest that BCG, LT or BV treatment in NOD mice at early age inhibit insulitis, onset and cumulative incidence of diabetes.
Adjuvants, Immunologic/pharmacology* ; Age Factors ; Animal ; Bee Venoms/pharmacology* ; Cholesterol/blood ; Diabetes Mellitus/prevention & control* ; Diabetes Mellitus/immunology ; Diabetes Mellitus, Insulin-Dependent/prevention & control* ; Diabetes Mellitus, Insulin-Dependent/immunology ; Disease Models, Animal ; Female ; Islets of Langerhans/pathology* ; Islets of Langerhans/drug effects ; Lymphotoxin/pharmacology* ; Mice ; Mice, Inbred NOD ; Mycobacterium bovis/immunology* ; Triglycerides/blood

The occurrence of immunoglobulin A nephropathy (IgAN) in patients with noninsulin dependent diabetes mellitus (NIDDM) is a rare event and of pathogenetic interest. It is not clear whether this is merely coincidence. We report here five patients with IgAN in NIDDM associated with or without diabetic glomerulosclerosis. All of the patients were Korean males. In three patients, diabetes mellitus was diagnosed at the same time with diagnosis of IgAN, and the known duration of the diabetes in the other two patients were three and seven years, respectively. There was no evidence of diabetic retinopathy in four patients, but it was found in one patient. In all cases, the diagnosis of IgAN was made by immunohistology.
Adult ; Biopsy ; Case Report ; Complement 3/analysis ; Diabetes Mellitus, Non-Insulin-Dependent/complications* ; Diabetic Nephropathies/pathology* ; Glomerular Mesangium/pathology ; Glomerulonephritis, IGA/pathology* ; Glomerulonephritis, IGA/etiology ; Human ; IgG/analysis ; Kidney Glomerulus/pathology ; Male ; Microscopy, Fluorescence ; Middle Age

The diagnosis of diabetic nephropathy (DN) is almost always based on clinical grounds. The diagnosis is supported by a long history of diabetes, evidence of target organ damage and proteinuria preceding azotemia. The validity of this clinical approach is well established in insulin dependent diabetes mellitus but not in non-insulin dependent diabetes mellitus (NIDDM). It is thus important to determine which patients with NIDDM accompanied by non-diabetic renal disease (NDRD) should have a biopsy. However, factors clinically associated with NDRD in patients with NIDDM remain unclear. Therefore we reviewed clinical data, laboratory data and renal biopsies from 22 NIDDM patients who underwent renal biopsy between 1992 and 1998 in Wonju Christian Hospital. From this data, we identified important features that would discriminate between DN and NDRD. There were 8 women and 14 men. Age ranged from 33 to 68 (51.2 +/- 10.7) years. The duration of diabetes at biopsy ranged from 0 to 13 (4.2 +/- 4.2) years. Nephrotic syndrome was present in 13 patients. The patients with NDRD (n = 14) and DN (n = 8) had comparable 24-hour proteinuria, 24-hour albuminuria, creatinine clearance, serum creatinine, albumin, as well as incidences of neuropathy and hypertension. The significant factors that predict the NDRD included a short duration of the diabetes mellitus, the presence of dysmorphic red blood cells in urine, the absence of retinopathy and HbA1c below 9% (p < 0.05, respectively). NDRD included IgA nephropathy (n = 6), minimal change disease (n = 3), membranous nephropathy (n = 3), membranous lupus nephritis (n = 1) and acute interstitial nephritis (n = 1). Multiple logistic regression analysis revealed that the short duration of DM and the absence of retinopathy were factors significantly associated with NDRD. In summary, when there is a short duration of diabetes mellitus, or an absence of retinopathy seen in patients with NIDDM, then renal biopsy in diabetic patients aids in the detection of NDRD.
Adult ; Aged ; Biopsy ; Diabetes Mellitus, Non-Insulin-Dependent/complications* ; Diabetic Nephropathies/diagnosis ; Diagnosis, Differential ; Female ; Human ; Kidney/pathology ; Kidney Diseases/pathology ; Kidney Diseases/diagnosis ; Kidney Diseases/complications* ; Male ; Middle Age

Due to their high immunostimulatory ability as well as the critical role they play in the maintenance of self-tolerance, dendritic cells have been implicated in the pathogenesis of autoimmune diseases. The non-obese diabetic (NOD) mouse is an animal model of autoimmune type 1 diabetes, in which pancreatic beta cells are selectively destroyed mainly by T cell-mediated immune responses. To elucidate initiation mechanisms of beta cell-specific autoimmunity, we attempted to generate bone marrow-derived dendritic cells from NOD mice. However, our results showed low proliferative response of NOD bone marrow cells and some defects in the differentiation into the myeloid dendritic cells. NOD dendritic cells showed lower expressions of MHC class II, B7-1, B7-2 and CD40, compared with C57BL/6 dendritic cells. In mixed lymphocyte reactions, stimulatory activities of NOD dendritic cells were also weak. Treatment with LPS, INF-gamma and anti-CD40 stimulated NOD dendritic cells to produce IL-12p70. The amount of IL-12, however, appeared to be lower than that of C57BL/6. Results of the present study indicated that there may be some defects in the development of NOD dendritic cells in the bone marrow, which might have an impact on the breakdown of self tolerance.
Animal ; Autoimmune Diseases/pathology ; Autoimmune Diseases/immunology ; Bone Marrow Cells/pathology* ; Bone Marrow Cells/immunology* ; Bone Marrow Cells/chemistry ; Cell Differentiation/immunology ; Cell Differentiation/drug effects ; Dendritic Cells/pathology* ; Dendritic Cells/immunology* ; Dendritic Cells/chemistry ; Diabetes Mellitus, Insulin-Dependent/pathology* ; Diabetes Mellitus, Insulin-Dependent/immunology ; Enzyme-Linked Immunosorbent Assay ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Interleukin-12/analysis ; Interleukin-4/pharmacology ; Lipopolysaccharides/pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Obesity