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Biomedical subjects

W Y Fujimoto

Publications and source records attributed to W Y Fujimoto.

At least 55 records · Page 3Linked to original sources
PubMed1993

Evidence for selective release of rodent islet amyloid polypeptide through the constitutive secretory pathway.

To determine the potential for differential release of islet amyloid polypeptide and insulin, we performed studies in rat islet monolayer cultures under conditions known to impair regulated beta-cell secretion. In inhibiting concentrations of epinephrine or the absence of calcium, islet amyloid polypeptide was secreted through a constitutive pathway while insulin was not. These findings suggest a mechanism for persistent islet amyloid polypeptide secretion and amyloid accumulation when regulated insulin release is impaired as in Type 2 (non-insulin-dependent) diabetes mellitus and insulinomas.

Amyloid↗
PubMed1993

Effect of heparin on insulin-glucose interactions measured by the minimal model technique: implications for reproducibility using this method.

The minimal model technique permits investigation of glucose and insulin interactions during a frequently sampled intravenous glucose tolerance test (FSIGT). The model allows measurement of several important variables including insulin sensitivity (SI), glucose effectiveness at basal insulin (SG), and glucose effectiveness at zero insulin (GEZI). In addition, from the FSIGT, first-phase insulin secretion (AIRglucose) and the glucose disappearance constant (Kg) can be estimated. The estimates obtained using the minimal model technique could be of importance in understanding potential relationships between carbohydrate and lipid metabolism. In studying lipoprotein lipase (LPL) activity and mass as one of the elements of lipid metabolism, heparin administration is necessary. However, the effect of administration of this agent on factors important in carbohydrate metabolism has not been fully elucidated. Therefore, to assess the effect of heparin on insulin-glucose interactions, we performed paired studies in which subjects randomly underwent FSIGT studies 20 minutes following bolus injections of heparin or saline. None of the measured parameters was influenced by heparin administration just before the FSIGT. Since these estimates were not affected by heparin administration, these studies also permitted assessment of the coefficient of variation of replicate analysis for all values generated using the minimal model technique. The coefficients of variation of replicate analysis calculated from these two studies were 16.9% for SI, 16.6% for SG, 18.3% for GEZI, 20.6% for AIRglucose, and 14.5% for Kg. These results suggest that heparin can be administered as part of a procedure that would allow concurrent assessment of various aspects of both carbohydrate and lipid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Influences of height and gender on normal nerve conduction studies.

Our purpose was to examine the effects of gender on nerve conduction results in healthy subjects. Fifty-four men, mean age 60.2 years and mean height 167cm, were compared with 62 women, mean age 62.2 years and mean height 153cm. We studied median, ulnar, sural, peroneal, and tibial nerves. Analyzing the raw data, women had significantly faster conduction velocities than men for all nerves except median motor (p < 0.05) three of four sensory amplitudes were larger in women and two of four motor amplitudes were larger in men (p < 0.05). After adjustment of the data for height, most statistically significant differences in conduction velocity disappeared, although differences in amplitude persisted. We conclude that most gender differences in nerve conduction velocity can be largely explained by height, whereas amplitude differences persist despite correction for height, temperature, and age.

Aged↗
PubMed1992

The growing prevalence of non-insulin-dependent diabetes in migrant Asian populations and its implications for Asia.

Many of the prevalence studies of diabetes in Asian populations are reviewed. When compared to Whites, Asians have an even greater predominance of non-insulin-dependent (NIDDM) over insulin-dependent diabetes (IDDM). Diabetes prevalence is higher among migrant Asians than in their homelands, and is often higher than in the majority population of their new homes. It is hypothesized that when a vulnerable population experiences environmental influences accompanying 'westernization', insulin resistance and eventually glucose intolerance develop. Asians are postulated to be a vulnerable ethnic group. Since many portions of Asia are also becoming westernized, it is postulated that insulin resistance and glucose intolerance will become more common in Asia. If this prediction is correct, then NIDDM will be a major health problem in Asia in the near future.

Asia↗
PubMed1992

Height is an independent risk factor for neuropathy in diabetic men.

Height may increase the risk of diabetic polyneuropathy, but previous studies are inconclusive. Our purposes were to further examine the hypothesis that height (HT) is an independent risk factor for diabetic polyneuropathy and to determine which electrophysiologic measures are influenced by HT in diabetic subjects. We studied 170 Japanese American men (ages 43-73 years, mean 61) including: 69 diabetic men (mean HT 166 cm), 54 normal men (mean HT 167 cm), and 47 men with impaired glucose tolerance (IGT) (mean HT 164 cm), measuring 28 nerve conduction study (NCS) parameters. We used data from normal men in developing regression models to adjust NCS parameters for HT, age, and temperature. Factor analysis was employed to reduce the 28 NCS parameters to five physiologically meaningful factors, one of which, a factor representing median and peroneal sensory amplitudes, was significantly correlated with HT (r = -0.38, P = 0.0011) in diabetic men; taller subjects having smaller sensory nerve amplitudes. No significant correlation was found between this factor and body mass index. This factor had no correlation with HT in normal or IGT men. Our data do not confirm previous reports of associations between HT and slowed motor conduction velocities in diabetic subjects. This study does, however, support the hypothesis that HT is an independent risk factor for sensory polyneuropathy in diabetic subjects.

Body Height↗
PubMed1992

Effect of glyburide and omega 3 fatty acid dietary supplements on glucose and lipid metabolism in patients with non-insulin-dependent diabetes mellitus.

Using a random crossover design, we examined the effects of glyburide for 4 wk on glucose, insulin, lipid, and lipoprotein metabolism in 10 men with non-insulin-dependent diabetes (NIDDM) receiving dietary fish-oil concentrates containing omega 3 (n-3) fatty acids (8 g/d). Compared with glyburide alone, fasting plasma glucose concentrations increased with fish oil. Although glyburide with fish oil decreased fasting glucose concentrations, they did not return to baseline. Basal insulin concentrations were unaltered by fish oil without or with glyburide; however, postprandial insulin concentrations were decreased by fish oil. Although total cholesterol and triglyceride concentrations were unchanged, very-low-density-lipoprotein cholesterol concentrations decreased and low-density-lipoprotein cholesterol rose and apolipoprotein B concentrations trended higher. Thus, glyburide only partially rectified the impaired fuel homeostasis associated with fish-oil supplements in patients with NIDDM. Therefore, we do not recommend intake of fish oil concentrates containing n-3 fatty acids in patients with NIDDM.

Aged↗
PubMed1992

Human lipoprotein lipase: relationship of activity, heparin affinity, and conformation as studied with monoclonal antibodies.

The objective of this study was to investigate how a conformational change in lipoprotein lipase (LPL) affects its molecular functions. Monoclonal antibodies (MAbs) were raised against purified bovine milk lipoprotein lipase. MAb 5D2 bound to human and bovine LPL both before and after denaturation of LPL. MAb 5F9 also recognized LPL from both species, but only after denaturation of the antigen, suggesting that a conformational change led to exposure of a previously hidden epitope. The MAbs were used in two sandwich enzyme-linked immunosorbent assays (ELISAs). One ELISA used the same MAb (5D2) to coat the plate and detect the bound antigen. This ELISA thus required the same epitope to be present in duplicate for detection (as would be the case with a dimeric antigen). The second ELISA used MAb 5F9 to coat the plate and MAb 5D2 to detect the antigen. This ELISA detected LPL only after it had been denatured. By measuring the same sample before and after denaturation with guanidine hydrochloride (GuHCl) in the 5F9 ELISA, and subtracting one from the other, a measure of native LPL was obtained. In inactivation experiments using human LPL, activity and the measure of LPL mass obtained in the 5D2 ELISA decreased and were related inversely to the measured mass obtained in the 5F9 ELISA which increased, indicating that loss of activity is closely linked to dimer dissociation and loss of native conformation. The effect of conformation and dimeric structure on LPL-heparin interaction was studied by heparin-Sepharose chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Educational attainment and the risk of non-insulin-dependent diabetes or coronary heart disease in Japanese-American men.

Japanese-American men have higher rates of non-insulin-dependent diabetes mellitus and coronary heart disease than same-aged men in Japan. Associations of educational attainment with either non-insulin-dependent diabetes mellitus or coronary heart disease were examined in a sample of 229 second-generation Japanese-American men (aged 45 to 74 years) living in King County, Washington (1984 through 1985). Men with a terminal school education showed higher frequencies of both disease compared to men with any college education and to men with high school educations. Occupation, income, diet, physical activity, weight, insulin, lipids, and lipoproteins were examined to determine whether they could account for the observed associations of educational attainment with disease. Logistic regression analysis indicates that the association of educational attainment with risk of coronary heart disease is explained, in part, by the larger average body mass index, higher total and VLDL triglyceride, and lower HDL and HDL-2 cholesterol observed in men with technical school educations compared to the other men. The association of educational attainment with risk of non-insulin-dependent diabetes is not explained by any of the factors examined. The findings suggest that attainment of a college education ameliorates some of the negative effects of westernization on the health of Japanese-American men.

Aged↗
PubMed1992

Ophthalmoscopy versus fundus photographs for detecting and grading diabetic retinopathy.

Reported here is the agreement between three examination methods chosen to detect and grade diabetic retinopathy in 124 subjects with type II (noninsulin-dependent) diabetes mellitus. These three examination methods include ophthalmoscopy (indirect and direct) by a retina specialist, seven standard field fundus photographs read by the same retina specialist, and the same photographs read by a trained photographic grader at the Fundus Photograph Reading Center. For the 59 subjects examined with all three methods, these results indicated fair to good (kappas, 0.69-0.84) agreement between the retina specialist's and trained grader's reading of photographs, fair to good (kappas, 0.58-0.79) agreement between the retina specialist's ophthalmoscopic findings and the specialist's reading of photographs, and fair (kappas, 0.49-0.62) agreement between the retina specialist's ophthalmoscopic findings and the trained grader's reading of fundus photographs. Analysis of the disagreements confirmed earlier reports that ophthalmoscopy misses approximately 50% of eyes with microaneurysms only. Other disagreements resulted from the trained grader's overreading photographs of eyes with lesions simulating diabetic retinopathy. Of the 393 total subjects (diabetic and nondiabetic) in this study, such lesions were seen with ophthalmoscopy in six eyes of six subjects (2.4% of diabetic patients and 1.1% of nondiabetic subjects). The authors believe at least one definite retinal microaneurysm should be present in one eye before establishing the diagnosis of diabetic retinopathy in diabetic patients.

Aged↗
PubMed1992

Factor analysis. A methodology for data reduction in nerve conduction studies.

Analyzing multiple nerve conduction study parameters individually is statistically problematic. The goal of this study was to develop a useful factor analysis scheme for assessment of nerve conduction study abnormalities in diabetic neuropathy. Hypotheses were: (1) factor analysis produces a few physiologically meaningful factors, (2) there are associations between factors and markers of diabetic severity and (3) clinical impressions are related to factor scores. We studied 165 Japanese-American men: 52 nondiabetic, 66 diabetic and 47 with impaired glucose tolerance. One author (W.C.S.) obtained 28 nerve conduction study parameters in all subjects and factor analysis extracted five factors from these parameters. These factors were related to conduction velocities (factor 1), distal ulnar function (factor 2), sensory amplitudes (factor 3), distal median function (factor 4) and distal peroneal function (factor 5); together, they explain 57% of the variability in the total data. Diabetic factor scores were significantly (P less than 0.05) below that of the controls and correlations with fasting blood sugar were significant at the P less than or equal to 0.001 level. Use of this technique promises to permit sensible analysis of large amounts of data in clinical studies of diabetic and other types of polyneuropathy.

Age Factors↗
PubMed1991

Effects of sodium butyrate on proliferation-dependent insulin gene expression and insulin release in glucose-sensitive RIN-5AH cells.

A rat islet tumor subclone, RIN-5AH-T2-B, was cultured with 2 mmol/liter of the proliferation-arresting compound sodium butyrate (NaB). Insulin gene expression and glucose-stimulated insulin release were analyzed and compared with logarithmically proliferating and confluent control cells cultured without NaB. Logarithmically proliferating control cells revealed high insulin gene expression. In the presence of amino acids, these cells showed a dose-dependent insulin response to glucose with a half-maximal and maximal 6.5-fold stimulation by 0.8 and 5.6 mmol/liter D-glucose, respectively. However, as the control cells approached growth arrest, insulin gene expression subsided to below detectability, an occurrence that is associated with decreased insulin release and accumulation of cells in the G1 phase of the cell cycle. In contrast, NaB-arrested cells showed continuous insulin gene expression throughout the experiment. Despite this, insulin release in response to glucose was lost. NaB revealed a biphasic effect on the cell-cycle: after an initial leaky G1 arrest during the first 24 h, the 5AH-B cells were arrested in G2 during the following 3 days. These data suggest that insulin gene expression and glucose-stimulated insulin release are affected by the cell cycle. These glucose-sensitive RIN-5AH-T2-B cells may be useful in studies of insulin secretion and gene regulation.

Animals↗
PubMed1991

Effect of statistical methodology on normal limits in nerve conduction studies.

Mean +/- 2 standard deviations (SD), which relies on a Gaussian distribution, has traditionally been used to derive normal limits for nerve conduction studies. Our purpose was to examine skew in nerve conduction study (NCS) parameters, and to compare normal limits derived by several alternative methods. We examined 22 NCS parameters from 75 asymptomatic, nondiabetic men (controls). The coefficient of skewness (g1) was significantly positive (P less than 0.10, two-tailed test) in 5 of 8 amplitude and 6 of 8 latency measurements. Transformation reduced g1 in 19 of 22 parameters, and was optimal when g1 was closest to zero. For each measurement, ideal normal limits were defined as mean +/- 2 SD of the optimally transformed data of the control subjects. The percentage of 66 diabetic subjects classified as abnormal by the raw data, but normal by the ideal normal limits, was the positive misclassification rate; while the percentage considered normal by the raw data, but abnormal by the ideal normal limits, was the negative misclassification rate. Mean +/- 2 SD of the raw data produced up to 11% positive misclassifications and 12% negative misclassifications. When the range of observed values was used, up to 6% positive misclassifications and 13% negative misclassifications were found, while the 2.5 or 97.5 percentile values produced up to 10% positive misclassifications and 13% negative misclassifications. We conclude that analyses using the raw data to derive normal limits result in an unacceptable rate of misclassification. Normal limits should be derived from the mean +/- 2 SD of the optimally transformed data.

Aged↗
PubMed1991

Glucose intolerance and diabetic complications among Japanese-American women.

The prevalence of glucose intolerance and diabetic complications was determined in second-generation Japanese-American (Nisei) women and compared to previously obtained results in Nisei men. A volunteer study sample of 191 Nisei women 45-74 years old was enrolled from a study population of 1489 Nisei women born 1913-1942, raised and educated in the U.S., and residing in King County, Washington. The enrolled sample included 72 with normal glucose tolerance, 67 with impaired glucose tolerance (IGT), and 52 with non-insulin-dependent diabetes. A random sample was also drawn from the study population to form a reference sample of 157 women. Based upon observations in the reference and enrolled samples, an estimated 16% of Nisei women in the study population have diabetes and 40% IGT. These rates compare to 20% diabetes and 36% IGT previously estimated for Nisei men 45-74 years old. The prevalence of cardiovascular disease (hypertension, peripheral vascular disease, and/or coronary heart disease) was highest among diabetic women, lowest in those with normal glucose tolerance, and intermediate in women with IGT. In comparison to diabetic men, there was a significantly lower frequency of neuropathy, peripheral vascular disease, and coronary heart disease in diabetic women. However, hypertension occurred equally often in both. Thus Japanese-American men and women 45-74 yr old have a similar prevalence of glucose intolerance, although less severe in women, and complications, except for hypertension, are reduced in women.

Adult↗
PubMed1991

Glucose stimulates and potentiates islet amyloid polypeptide secretion by the B-cell.

Islet amyloid polypeptide (IAPP) has been shown to be actively secreted by the pancreatic B-cell along with insulin. To determine whether the modulation of B-cell IAPP secretion is similar to that of insulin, we assessed IAPP release in response to glucose at 4 different concentrations (1.67, 5.5, 8.8 and 16.7 mM) and to non-glucose secretagogues at different glucose concentrations in a neonatal rat islet monolayer culture preparation. Glucose alone stimulated IAPP and insulin secretion in a dose dependent fashion with maximal release for both peptides occurring at 8.8 mM. B-cell secretion of IAPP in response to arginine, isobutylmethylxanthine or both together was potentiated by increasing glucose concentrations from 1.67 to 16.7 mM. This same pattern of glucose potentiation was observed for insulin secretion. The data indicate that the pattern of peptide responses of cultured neonatal B-cells to glucose is similar for both IAPP and insulin release. Furthermore, the data suggest that glucose is capable of potentiating B-cell secretion of both IAPP and insulin.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Urinary catecholamines, plasma insulin and environmental factors in relation to body fat distribution.

The relationship of body fat distribution to insulin and the catecholamines, hormones that affect lipolysis differentially by fat site, was examined within an environmental context, including factors of medication use, physical activity, dietary intake, educational attainment, and age. Four cross-sectional body fat areas (cm2) were determined by three computed tomography (CT) scans (subcutaneous chest fat at the level of the nipples, subcutaneous and intra-abdominal fat at the level of the umbilicus, and subcutaneous left mid-thigh fat) in 191 second-generation Japanese-American men aged 45-74 years. The site-specific fat measurements were first examined in relation to use of beta-adrenergic antagonists, then to fasting plasma insulin and C-peptide levels and to urinary epinephrine and norepinephrine levels from a 24-h urine collection made during usual daily activities. Greater fat stores in the intra-abdominal area, even after adjustment for body mass index (BMI, weight/height2) and presence of coronary heart disease, were found to be related to use of beta-adrenergic antagonists. In men taking no adrenergic antagonists (n = 157), after adjustment for BMI, truncal fat measurements of the chest (partial r = -0.16, P less than 0.05) and intra-abdominal area (partial r = -0.21, P less than 0.05) were found to be inversely related to epinephrine, and intra-abdominal fat (partial r = 0.25, P less than 0.01) alone was directly related to fasting plasma insulin. With respect to other environmental variables, the significant inverse relationship of intra-abdominal fat (adjusted for BMI) with physical activity (partial r = -0.17, P less than 0.05) and the significant difference in intra-abdominal fat by educational attainment (college 102.3 +/- 5.7 vs no college 115.7 +/- 6.1 cm2, P = 0.03) became non-significant with adjustment, using multiple regression analysis, for insulin in the case of physical activity and epinephrine in the case of educational attainment. Thus, intra-abdominal fat showed a unique set of relationships to metabolic parameters which could be further related to certain environmental variables.

Adipose Tissue↗
PubMed1991

Relationship of absence or presence of a family history of diabetes to body weight and body fat distribution in type 2 diabetes.

In a study sample of second generation Japanese American men (age range 45-74 years), family history of diabetes in a sibling or parent was present in 69 men (24 of 79 normal men and 45 of 78 type 2 diabetic men, P less than 0.001). Both general adiposity and body fat distribution have been associated with type 2 diabetes. Our hypothesis was that the association of both overall adiposity and of larger specific regional fat deposits with type 2 diabetes would differ depending upon family history. The relationships between diabetes and differences in general adiposity (whether current or maximum lifetime body mass index or BMI, sum of skinfolds, or sum of computed tomography or CT fat areas) and between diabetes and body fat distribution (measured as abdominal and thigh circumferences, cross-sectional body fat areas by CT of thorax, abdomen, and thigh, and skinfold thicknesses of triceps, biceps, forearm, chest, subscapula, abdomen, and thigh) were more apparent in those men without a family history of diabetes than in those with a family history. In men without a family history, diabetic men had significantly higher values for several variables which assessed overall adiposity: current BMI (P less than 0.001), maximum lifetime BMI (P less than 0.001), sum of skinfolds (P less than 0.006), and sum of CT fat areas (P less than 0.015). In addition several measurements of upper truncal adiposity were significantly increased in diabetic men: abdominal circumference (P less than 0.004), thoracic (P less than 0.015) and abdominal (P less than 0.03) subcutaneous CT fat areas, intra-abdominal CT fat areas (P less than 0.001), and chest (P less than 0.03) and subscapular (P less than 0.0002) skinfold thicknesses. The results pertaining to those without a family history appear to be due to increased adiposity and associated larger specific regional fat depots leading to diabetes and lesser adiposity and smaller amounts of fat in the same regional depots protecting against diabetes.

Adipose Tissue↗
PubMed1990

Association of plasma triglyceride and C-peptide with coronary heart disease in Japanese-American men with a high prevalence of glucose intolerance.

In a community-based study of second-generation Japanese-American men known to have a high prevalence of both Type 2 (non-insulin-dependent) diabetes and impaired glucose tolerance, there was a highly significant association of coronary heart disease with glucose intolerance in a study sample of 219 men. Intra-abdominal cross sectional fat area determined by computed tomography was significantly elevated in men with coronary heart disease even after adjustment for glucose intolerance and body mass index (p = 0.026). Other differences that were significantly related to coronary heart disease after adjustment for glucose intolerance were lower high density lipoprotein cholesterol levels (p = 0.001), elevated total triglyceride and very low density lipoprotein triglyceride (p less than 0.001), and elevated fasting insulin and C-peptide levels p = 0.001. When these variables were tested in a stepwise multiple logistic regression model, significant independent associations with coronary heart disease were found only for total triglyceride and fasting C-peptide after adjustment for glucose tolerance status. Variables identified to be associated with coronary heart disease were interpreted as representing or manifesting an insulin resistant state. Thus, insulin resistance may be the underlying risk factor aetiologically linking glucose intolerance with coronary heart disease.

Alcohol Drinking↗