Kunizo Kataoka

Cell-mediated cytotoxic islet cell surface antibodies to human pancreatic beta cells

SummarySera containing islet cell surface antibodies show a complement-dependent cytotoxic reaction against islet cells, but it has not yet been clarified whether islet cell surface antibodies exhibit cell-mediated cytotoxicity to these cells. By 51Cr release assay we investigated whether islet cell surface antibodies showed a cytotoxic reaction to human pancreatic B cells (JHPI-1 clone) in the presence of normal human lymphocytes. The sera from 14 islet cell surface antibody-positive, 16 islet cell surface antibody-negative Type 1 (insulin-dependent) diabetic patients and 18 islet cell surface antibody-negative healthy subjects were studied. Four sera containing islet cell surface antibodies showed specific cytotoxicity above the mean +3SD value of healthy subjects, and the mean specific cytotoxicity of islet cell surface antibody-positive sera differed significantly from that of both islet cell surface antibody-negative groups. These results suggest that this cell-mediated cytotoxic mechanism may play an important role in the pathogenesis of Type 1 diabetes.

Exogenous insulin dose-dependently suppresses glucopenia-induced glucagon secretion from perfused rat pancreas

To clarify the role of insulin in modulating the glucagon response to glucose concentration changes, we investigated the effects of exogenous insulin (10 mU/mL, 100 mU/mL, and 3.3 U/mL) on responses to high glucose (5.6-->16.7 mmol/L), low glucose (5.6-->1.4 mmol/L), and arginine (10 mmol/L) stimulation using the perfused rat pancreas. Although glucagon levels were slightly suppressed by all of the exogenous insulin concentrations tested for the initial few minutes at 5.6 mmol/L glucose, baseline levels were maintained thereafter. Glucagon responses to high or normal glucose concentrations were not altered, but glucopenia-induced glucagon secretion was significantly suppressed as compared with that of controls (0.77 +/- 0.14 ng/min [10 mU/mL, n = 5], 0.55 +/- 0.14 ng/min [100 mU/mL, n = 5], 0.27 +/- 0.13 ng/min [3.3 U/mL, n = 5] v 1.38 +/- 0.20 ng/min [controls, n = 9], P < 0.05, respectively). The first phase of the glucagon response to arginine was potentiated (2.03 +/- 0.24 v 1.17 +/- 0.22 ng/min, P < .05) by 10 mU/mL exogenous insulin. The second phase of the glucagon response to arginine was significantly suppressed in the presence of higher concentrations of exogenous insulin (1.16 +/- 0.23 ng/min [100 mU/mL], 0.96 +/- 0.08 ng/min [3.3 U/mL] v 1.57 +/- 0.17 ng/min, P < .05, respectively). These results suggest that glucagon secretion is modified by the combined suppressive effects of glucose and insulin, although it is mainly glucose that mediates glucagon secretion in the physiological glucose range. Glucopenia- or arginine-induced glucagon secretion is suppressed by insulin.

Immunological aspect of non-obese diabetic mice: immune islet cell-killing mechanism and cell-mediated immunity

SummaryThe non-obese diabetic mouse is thought to be one of the best available animal models for human Type 1 (insulin-dependent) diabetes. By 51Cr release assay we investigated cell-mediated cytotoxicity to the islet cells of Balb/C mice, natural killer activity, and antibody-dependent cell-mediated cytotoxicity activity of spleen lymphocytes from pre-diabetic non-obese diabetic mice. The cell-mediated cytotoxicity to islet cells of non-obese diabetic mice was significantly higher than that of control ICR mice. In contrast, natural killer and antibody-dependent cell-mediated cytotoxicity activities of the spleen cells from the non-obese diabetic mice were significantly lower than those of ICR mice spleen cells. These results suggest that lymphocytes from non-obese diabetic mice were sensitized to the antigen of islet cells and that the non-specific cellular immunity of non-obese mice was reduced. They suggest also that this immune islet cell-killing mechanism may play an important role in the pathogenesis of diabetes in non-obese diabetic mice.

Influence of glycemic control and hypertension on urinary microprotein excretion in non-insulin-dependent diabetes mellitus

In order to evaluate the influence of glycemic control and hypertension on the development of diabetic nephropathy, we measured urinary excretion of albumin (AER) and other microproteins in non-insulin-dependent diabetes mellitus (NIDDM), and reexamined the 103 patients who had had AER less than 300 micrograms/min at the initial study 12-18 months later. AER in the patients with HbA1c greater than or equal to 7.5% increased significantly in both the normoalbuminuric (AER less than 30 micrograms/min) and microalbuminuric (30-300 micrograms/min) groups, whereas no significant change in AER was observed in the patients with HbA1c less than 7.5%. In the microalbuminuric group, AER in both hypertensive and normotensive patients increased significantly. In this group, the change in AER correlated positively with the change in alpha 1-microglobulin (alpha 1M). These results indicate that glycemic control has a greater influence on the development of nephropathy in its early stage than hypertension and that alpha 1M is as a good predictor of nephropathy as albumin.

Effect of α-adrenergic blockade on blood pressure, glucose, and lipid metabolism in hypertensive patients with non-insulin-dependent diabetes mellitus

Abstract To clarify the long-term effects of α-adrenergic blockade on blood pressure, glucose, and lipid metabolism, a slective α 1 -adrenergic inhibitor (prazosin, 1.0 to 2.0 mg/day in divided doses) was administered as a single antihypertensive agent to 10 (four men and six women, aged 52 to 76 years) hypertensive patients (systolic blood pressure [SBP] ≥ 150 mm Hg or diastolic blood pressure [DBP] ≥ 90 mm Hg) with non-insulin-dependent diabetes mellitus (NIDDM) for up to 20 weeks. Blood pressure, glucose tolerance and immunoreactive insulin (IRI) response to 75 gm oral glucose load, hemoglobin A 1 (Hb A 1 ), serum lipid profile, and serum apolipoprotein were examined before and after treatment. SBP and DBP were significantly reduced at 20 weeks after treatment with the selective α 1 -adrenergic inhibitor (SBP 167 ± 6 mm Hg versus 152 ± 7 mm Hg; DBP 81 ± 3 mm Hg versus 76 ± 3 mm Hg, ( p p α 1 -inhibitor treatment compared with the baseline data before treatment; the level of Hb A 1 was not significantly changed at 4 and 20 weeks after treatment. Total cholesterol and free fatty acid (FFA) concentrations were significantly reduced at 20 weeks (total cholesterol 213 ± 13 mg/dl versus 196 ± 10 mg/dl [5.52 ± 0.34 mmol/L versus 5.08 ± 0.26 mmol/L], FFA 0.67 ± 0.11 mEq/L versus 0.48 ± 0.11 mEq/L; p p p 1 , B, C 2 , C 3 , and E was observed during treatment. These data suggest that treatment with a selective α 1 -adrenergic inhibitor elicits a favorable effect on blood pressure and lipid metabolism without causing a deterioration in blood glucose control in hypertensive NIDDM patients.

Erythrocyte Aging Changes Evaluated by the Deoxyuridine Suppression Test

Many hematologic studies have shown that the erythrocyte count decreases while the size of the individual cell increases in the aged. This study was performed in order to (1) evaluate changes in the blood erythrocyte level and mean erythrocyte size in the elderly and (2) evaluate use of the deoxyuridine (dU) supression test to determine whether deficiency of vitamin B12or folate plays any role in age‐related changes of hematopoiesis. Selected for study were 102 healthy men whose ages ranged from 20 to 79 years. The erythrocyte count and hemoglobin level decreased significantly, whereas the mean corpuscular volume and mean corpuscular hemoglobin increased after 70 years of age. Fresh bone‐marrow cells were obtained from 10 young (20–38 yr) and 10 aged (70–82 yr) men. Wickramasinghes dU suppression test was modified by application of an automatic cell harvester. The results were normal in both groups. Thus, the route of dU to dTMP in a DNA synthetic pathway appeared intact, and there was no evidence of B142or folate deficiency in the aged to explain the observed macrocytosis. However, 3H‐thymidine uptake by nucleated bone‐marrow cells was significantly decreased, and the ratio of 3H‐uridine to 3H‐thymidine uptake was greater in the old group than in the young group. These results could be explained by altered nucleic acid metabolism (unbalanced cell growth) or by a change in the proportion of the different fractions of nucleated cells.

Elevated Serum Creatine Kinase Level in Diabetic Patients with Nephrotic Syndrome: A Role of Fluid Retention

Excerpt Elevation of serum levels of the MM isoenzyme of creatine kinase usually reflects the destruction of skeletal muscles. However, creatine kinase levels can increase without muscle destructio...