Y Iwashima

Asahikawa Medical University, Asahikawa, Hokkaido, Japan

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Publications (25)77.25 Total impact

  • Article: Type III hyperlipoproteinema with apolipoprotein E2/2 genotype in Japan.
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    ABSTRACT: Limited information is available concerning type III hyperlipoproteinemia (HLP) in the Asian population. Therefore, clinical and biochemical characteristics of type III HLP were examined in 16 Japanese patients. Mean plasma triglyceride (TG) and total cholesterol (chol) levels were 381 mg/dl and 253 mg/dl, respectively, and the mean very low density lipoprotein (VLDL)-chol/plasma TG ratio was 0.27, which were lower than those reported in Western countries. Eighty percent of the patients had high plasma remnant-like particles (RLP)-chol levels above 50 mg/dl and a high RLP-chol/plasma TG ratio above 0.1. Twelve patients (75.0%) were obese. Seven patients (43.8%) had type 2 diabetes mellitus and four patients (25.0%) had impaired glucose tolerance. Six patients (37.5%) had coronary heart disease (CHD), but none had peripheral vascular disease or xanthomas. TG-rich lipoproteins from type III HLP patients with diabetes mellitus stimulated cholesteryl ester synthesis by human macrophages significantly (p < 0.001) more than those from type III HLP patients without diabetes mellitus. In conclusion, the Japanese type III HLP patients had lower plasma TG and total chol levels and a lower VLDL-chol/plasma TG ratio, but CHD was more common. The patients were characterized by a high frequency of obesity and/or glucose intolerance. The TG-rich lipoproteins from type III HLP patients with diabetes mellitus were more atherogenic.
    Clinical Genetics 07/2002; 61(6):416-22. · 3.13 Impact Factor
  • Article: Downregulation of the voltage-dependent calcium channel (VDCC) beta-subunit mRNAs in pancreatic islets of type 2 diabetic rats.
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    ABSTRACT: The present study was undertaken to determine whether altered expression of the VDCC beta-subunits in pancreatic beta-cells could play a role in the changes in beta-cell sensitivity to glucose that occur with diabetes. Application of competitive RT-PCR procedure revealed that in normal Wistar rats, LETO and prediabetic OLETF rats, the beta(2)-subunit mRNA levels were 60-200-fold greater than the levels for the beta(3)-subunit. These findings suggest that the beta(2)-subunit as well as the beta-cell type VDCC1 alpha(1)-subunit may be the predominant form of the VDCC expressed in pancreatic beta-cells. The levels of mRNA encoding the beta-subunits and the beta-cell type alpha(1)-subunit as well as insulin were significantly reduced in diabetic rats. Perfusion experiments revealed that diabetic rats showed the higher basal insulin secretion and profoundly impaired insulin secretory responses to glucose compared with non-diabetic rats. Alternatively, impaired insulin secretory responses to glucose in high dose glucose-infused rats were recovered partly with the elevation of mRNA levels of the VDCC beta(2)- and beta(3)-subunits as well as the alpha(1)-subunit by the treatment with diazoxide. Thus, considering the possibility that the most striking effect of the VDCC alpha(1) beta-subunit coexpression in pancreatic beta-cells might occur on activation kinetics like the skeletal muscle, the impairment of further activation of the VDCCs to acute glucose challenge caused by the reduced expressions of the alpha(1) beta-subunits mRNAs in type 2 diabetic animals might be at least partly associated with the alterations in beta-cell sensitivity to glucose.
    Biochemical and Biophysical Research Communications 02/2001; 280(3):923-32. · 2.48 Impact Factor
  • Article: Detection of the association between a deletion polymorphism in the gene encoding angiotensin I-converting enzyme and advanced diabetic retinopathy.
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    ABSTRACT: We investigated the relationship between advanced diabetic retinopathy (ADR) and an angiotensin-converting enzyme (ACE) gene polymorphism in subjects with type 2 diabetes and ADR, pre-proliferative (PrePDR) or proliferative diabetic retinopathy (PDR) without overt nephropathy. Polymerase chain reactions were used to detect insertion/deletion (I/D) polymorphisms of the ACE gene. There was no difference in the frequency of II, ID, or DD genotypes, or of I and D alleles among subjects with type 2 diabetes without diabetic retinopathy (NDR) or with simple diabetic retinopathy (SDR) and non-diabetic controls. There was also no difference in the frequency of ACE genotypes among subjects with type 2 diabetes with NDR, or SDR and ADR. However, the frequency of the ACE DD genotype in ADR was significantly higher than that in controls (chi(2)=6.64, P=0.036). On the other hand, the frequency of the D allele in ADR was significantly higher than that in controls (chi(2)=6.33, P=0.012), NDR (chi(2)=4.18, P=0.041) and SDR (chi(2)=4. 89, P=0.027), respectively. These results indicate a significant relationship between the presence of the D allele polymorphism in the ACE gene and ADR in Japanese subjects with type 2 diabetes and no overt nephropathy.
    Diabetes Research and Clinical Practice 01/2001; 50(3):195-202. · 2.75 Impact Factor
  • Article: Advanced glycation end products-induced gene expression of scavenger receptors in cultured human monocyte-derived macrophages.
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    ABSTRACT: We investigated the effects of advanced glycation end products (AGEs) on the expression of oxidized low-density lipoprotein (OxLDL) receptors in human monocyte-derived macrophages and THP-1 cells treated with PMA. Both RT-PCR procedure and Northern blot analysis revealed that AGEs induced not only the gene expression of two major OxLDL receptors, macrophage scavenger receptor (MSR) class A and CD36, but also MSR-B I and lectin-like oxidized low-density lipoprotein receptor 1. Also, as a result of gel shift assay, AGEs increased transcriptional activities of AP-1, NF-kappaB, and peroxisome proliferator-activated receptor gamma. These findings indicate that AGEs-induced enhancement of these transcriptional activities might be involved in increased levels of mRNA for some of OxLDL receptors in THP-1-cells treated with PMA. The upregulated surface expression of these receptors on macrophage membranes was closely associated with increased uptake of modified LDL, and culminated in enhanced foam cell transformation. Thus, AGEs may be involved in the cause of variable levels of foam cell formation via the increased numbers of OxLDL receptors in accelerated atherosclerotic lesions of individuals with diabetes.
    Biochemical and Biophysical Research Communications 11/2000; 277(2):368-80. · 2.48 Impact Factor
  • Article: Advanced glycation end product-induced peroxisome proliferator-activated receptor gamma gene expression in the cultured mesangial cells.
    Y Iwashima, M Eto, S Horiuchi, H Sano
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    ABSTRACT: We identified the AGEs-induced expression of peroxisome proliferator-activated gamma (PPAR gamma) in the cultured mesangial cells using reverse transcription-polymerase chain reaction, electrophoretic mobility shift assay (EMSA), and Western immunoblotting. Administration of AGEs-BSA into the cultured mesangial cells resulted in an increase in the levels of mRNA and proteins for PPAR gamma in a dose-dependent manner. Specific bands which indicate the protein binding to PPAR gamma responsive element (PPRE) in the nuclear extracts were also detected in AGEs-BSA-treated mesangial cells, but not found in BSA-treated cells by EMSA. Antioxidants, NAC, PDTC, and aminoguanidine, attenuated the gene expression and activity of PPAR gamma induced by AGEs. These results indicate that PPAR gamma was induced and activated by the oxidative signal(s) evoked by AGEs-ligand-receptor interactions. AGEs-induced gene expression of PPAR gamma and the signal intensity of PPAR gamma and PPRE complex were attenuated furthermore by protein kinase C inhibitors, calphostin C and staurospolin, but not abolished completely, indicating that both signal transduction pathways through the induction of PKC activation and independent of PKC activation were involved in the AGEs-mediated expression and activation process of PPAR gamma. AGEs also increased the gene expression of smooth muscle alpha-actin, which is a marker for phenotypic change in mesangial cells. It is suggested therefore that AGEs-induced transcription factor as the oxidative stress may have a role in the differentiation of mesangial cells.
    Biochemical and Biophysical Research Communications 11/1999; 264(2):441-8. · 2.48 Impact Factor
  • Article: [RLP-C (remnant-like particle cholesterol)].
    Y Iwashima
    Nippon rinsho. Japanese journal of clinical medicine 01/1998; 56 Suppl 3:262-8.
  • Article: [Streptozocin-induced diabetes].
    Y Iwashima
    Nippon rinsho. Japanese journal of clinical medicine 01/1998; 56 Suppl 3:732-7.
  • Article: Remnant-like particles (RLP) from NIDDM patients with apolipoprotein E3/3 phenotype stimulate cholesteryl ester synthesis in human monocyte-derived macrophages.
    M Saito, M Eto, M Okada, Y Iwashima, I Makino
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    ABSTRACT: We tested the ability of remnant-like particles (RLP) from NIDDM patients to stimulate cholesteryl ester synthesis in human monocyte-derived macrophages. Six NIDDM patients were studied together with 7 non-diabetic subjects. All had apolipoprotein (apo) E3/3 phenotype. RLP were isolated using an immunoaffinity gel mixture of anti apo B-100 and anti apo A-1 monoclonal antibodies coupled to Sepharose 4B. Plasma levels of triglyceride, total cholesterol (chol) and high density lipoprotein-chol were not statistically different, but plasma levels of RLP-chol were significantly (p < 0.05) higher in NIDDM patients (10.5 +/- 2.2 mg/dl) than in non-diabetic controls (5.0 +/- 1.7 mg/dl). The effects of RLP from NIDDM patients on macrophage cholesteryl ester synthesis were estimated. 14C-oleate incorporation into cholesteryl esters in macrophages was significantly (p < 0.01) higher in NIDDM patients with apo E3/3 (0.326 +/- 0.037 nmole/mg cell protein) than in non-diabetic controls with apo E3/3 (0.181 +/- 0.011 nmole/ mg cell protein). It is suggested that RLP from NIDDM play a role in the accumulation of cholesteryl esters and are one of the risk factors for the acceleration of atherosclerosis in NIDDM.
    Artery 02/1996; 22(3):155-63.
  • Article: Increased frequency of apolipoprotein epsilon 2 allele in non-insulin dependent diabetic (NIDDM) patients with nephropathy.
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    ABSTRACT: The genetic polymorphism of apolipoprotein E (epsilon 2, epsilon 3 and epsilon 4) is associated with lipid abnormalities. It has been suggested that lipid abnormalities may contribute to the development and progression of kidney diseases, including diabetic nephropathy. Thus, in this study we compared the apo E allele frequencies among 146 non-insulin-dependent diabetic (NIDDM) patients with nephropathy, 135 NIDDM patients without nephropathy and 576 of the general Japanese population. The epsilon 2 allele frequency was significantly higher in diabetic patients with nephropathy (7.2%) and with renal failure (9.7%) than in diabetic patients without nephropathy (2.6%) and in the general Japanese population (3.7%). It is concluded that there is a possibility that the epsilon 2 allele is associated with nephropathy in NIDDM.
    Clinical Genetics 01/1996; 48(6):288-92. · 3.13 Impact Factor
  • Article: Increased frequency of apolipoprotein ε2 allele in non‐insulin dependent diabetic (NIDDM) patients with nephropathy
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    ABSTRACT: The genetic polymorphism of apolipoprotein E (ε2, ε3 and ε4) is associated with lipid abnormalities. It has been suggested that lipid abnormalities may contribute to the development and progression of kidney diseases, including diabetic nephropathy. Thus, in this study we compared the apo E allele frequencies among 146 non-insulin-dependent diabetic (NIDDM) patients with nephropathy, 135 NIDDM patients without nephropathy and 576 of the general Japanese population. The ε2 allele frequency was significantly higher in diabetic patients with nephropathy (7.2%) and with renal failure (9.7%) than in diabetic patients without nephropathy (2.6%) and in the general Japanese population (3.7%). It is concluded that there is a possibility that the ε2 allele is associated with nephropathy in NIDDM.
    Clinical Genetics 11/1995; 48(6):288 - 292. · 3.13 Impact Factor
  • Article: Reduced levels of messenger ribonucleic acid for calcium channel, glucose transporter-2, and glucokinase are associated with alterations in insulin secretion in fasted rats.
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    ABSTRACT: Expression of the genes for voltage-dependent calcium channels (VDCCs), glucose transporter-2 (GLUT2), and glucokinase was studied in pancreatic islets obtained from normal rats after periods of fasting and refeeding using a competitive polymerase chain reaction procedure. A 72-h fast induced about a 3-fold decrease in the beta-cell/neuroendocrine type VDCC alpha 1-subunit and GLUT2 messenger RNA (mRNA) levels and about a 2-fold decrease in insulin and glucokinase mRNA levels compared to those in fed and refed rats. No significant differences were found in beta-actin and the cardiac-type VDCC alpha 1-subunit mRNA levels among fed, fasted, anf refed rats. We also studied insulin secretion from the isolated perfused pancreata obtained from these animals. We found an elevated threshold and decreased insulin release in response to a stepwise increase in glucose concentrations in the isolated perfused pancreata obtained from fasted rats. Fasting also resulted in a dramatic decrease in insulin secretory responses during the application of an L-type VDCC agonist, Bay K8644 (1 microM). Furthermore, fasting resulted in a significant decrease in both 45Ca2+ uptake by the isolated islets and insulin release from the islets. A strong positive correlation was observed between glucose-induced 45Ca2+ uptake and insulin output among the animals studied. On the other hand, after a 24-h refeeding, significant increases in the insulin secretory response to glucose and Bay K8644 were found, with a normalization in mRNA levels for these components. It, thus, appears that the alterations in beta-cell sensitivity to glucose that occur with fasting and refeeding are the result of complex metabolic alterations in the islet associated with reductions in expression of at least in part the beta-cell/neuroendocrine type VDCC in addition to two components of the glucose-sensing apparatus, including glucokinase and GLUT2, and the reduction in mRNA for insulin.
    Endocrinology 10/1994; 135(3):1010-7. · 4.46 Impact Factor
  • Article: Expression of calcium channel mRNAs in rat pancreatic islets and downregulation after glucose infusion.
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    ABSTRACT: Recent studies have shown that two different voltage-dependent Ca2+ channels are expressed in pancreatic islets, the beta-cell/neuroendocrine-brain and the cardiac subtypes. The effects of chronic hyperglycemia on the levels in pancreatic islets of the mRNAs encoding the alpha 1-subunits of the beta-cell and cardiac subtype Ca2+ channels were studied in rats made hyperglycemic by infusion of glucose for 48 h. A competitive reverse transcriptase-polymerase chain reaction procedure was used to obtain quantitative data on the levels of these two transcripts in islets obtained from individual rats. The quantitative polymerase chain reaction data indicate that the levels of mRNA encoding the alpha 1-subunit of the beta-cell Ca2+ channel are 2.5-fold greater than those for the cardiac subtype. The levels of beta-cell Ca2+ channel mRNA were 72.9% lower in the glucose-infused animals when compared with the saline-infused animals (P < 0.005) and those of the cardiac channel were 72.1% lower in the animals infused with glucose (P < 0.02). In contrast, glucose infusion resulted in a twofold increase in insulin mRNA levels and did not significantly alter levels of beta-actin mRNA. In situ hybridization studies revealed that the mRNAs for these two Ca2+ channels are expressed at higher levels in normal rat islets than in the surrounding acinar tissue, which suggests that the observed changes in mRNA levels occur within cells of the pancreatic islet. To assess the possible functional consequences of this reduction in expression of mRNA for the Ca2+ channels, the insulin secretory responses of perfused pancreases to the Ca2+ channel agonist Bay K8644 were studied.(ABSTRACT TRUNCATED AT 250 WORDS)
    Diabetes 07/1993; 42(7):948-55. · 8.29 Impact Factor
  • Article: Effects of apolipoprotein E polymorphism on plasma lipoprotein(a) levels.
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    ABSTRACT: Effects of apolipoprotein E (apo E) genetic polymorphism on plasma lipoprotein(a) (Lp(a)) levels were investigated in 305 civil service workers (158 men and 147 women). Plasma Lp(a) levels were measured by ELISA. Apo E phenotypes were determined from plasma by isoelectric focusing, Western blotting and immunostaining, as we previously reported. A total of 305 subjects were divided into the three apo E groups; apo E2 group (n = 19 for apo E3/2 and n = 4 for apo E4/2), Apo E3/3 group (n = 224) and apo E4/3 group (n = 58). Mean levels of plasma Lp(a) were 14.2 mg/dl. Plasma Lp(a) levels were significantly lower in the apo E2 group (6.6 mg/dl) than in the apo E3/3 (15.1 mg/dl) and E4/3 (13.7 mg/dl) groups. Plasma total cholesterol (T-chol) and low density lipoprotein (LDL)-chol levels were significantly lower in the apo E2 group than in the apo E4/3 group and tended to be highest in the apo E4/3 group. A significant positive correlation was noted between plasma Lp(a) levels and plasma LDL-chol levels, indicating that the effects of apo E polymorphism on plasma Lp(a) levels were parallel to its effects on plasma LDL-chol levels. In women plasma Lp(a) levels were significantly lower in the apo E2 group than in the apo E3/3 and E4/3 groups, whereas in men plasma Lp(a) levels tended to be lower in the apo E2 group but no significant difference was noted among the three apo E groups. It is concluded that plasma Lp(a) levels are, at least in part, modulated by apo E polymorphism (particularly apo E2) and that there is a gender difference in the effects of apo E polymorphism on plasma Lp(a) levels.
    Artery 02/1993; 20(6):324-36.
  • Article: Polyol pathway in tissues of spontaneously diabetic Chinese hamsters (Cricetulus griseus) and the effect of an aldose reductase inhibitor, ONO-2235.
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    ABSTRACT: 1. Sorbitol and fructose levels were significantly elevated in the lens, the sciatic nerve, the retina and the kidney of diabetic Chinese hamsters and inositol level was significantly decreased in the lens and sciatic nerve of diabetics. 2. The activity of an aldose reductase in the kidney was not different between normal and diabetic Chinese hamsters. 3. An aldose reductase inhibitor (ONO-2235) had no effect in sorbitol, fructose and inositol contents of all these tissues from diabetic Chinese hamsters. 4. These results suggest that diabetic Chinese hamsters produce polyol accumulation in tissues but that there is a clear species-specific difference to inhibition of aldose reductase.
    Comparative biochemistry and physiology. B, Comparative biochemistry 02/1991; 98(4):637-40.
  • Article: Effects of probucol on plasma lipids and lipoproteins in familial hypercholesterolemic patients with and without apolipoprotein E4.
    M Eto, T Sato, K Watanabe, Y Iwashima, I Makino
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    ABSTRACT: It has been reported that total cholesterol (Chol) response to probucol is greater in familial hypercholesterolemic (FH) patients with apo E4 than in those without apo E4. We further examined the effect of probucol on plasma triglyceride (TG) and lipoprotein-Chol levels as well as total Chol levels in heterozygous FH patients with apo E4 (n = 14 for apo E4/3, n = 1 for apo E4/4) and without apo E4 (n = 31 for apo E3/3). Probucol was administered in a dosage of 500 mg twice daily for 3 months. The reduction in total Chol levels was significantly greater in FH patients with apo E4 (-90 mg/dl, -27.5%) than in those without apo E4 (-41 mg/dl, -13.7%). The reduction in low density lipoprotein (LDL)-Chol levels was also significantly greater in FH patients with apo E4 (-73 mg/dl vs. -34 mg/dl). There was a significant difference in the change in TG and very low density lipoprotein (VLDL)-Chol levels with treatment between the FH patients with apo E4 (-37 and -8 mg/dl, respectively) and without apo E4 (+8 and +2 mg/dl, respectively). However, there was no significant difference in the reduction in HDL-Chol levels between the 2 groups (-9 mg/dl vs. -9 mg/dl). It is concluded that FH patients with apo E4 showed the greater reduction in plasma TG levels as well as total Chol levels with probucol treatment than those without apo E4, and that the greater reduction in total Chol levels in them, as reported previously, was mainly due to the greater reduction in LDL-Chol levels and slightly due to that in VLDL-Chol levels.
    Atherosclerosis 10/1990; 84(1):49-53. · 3.79 Impact Factor
  • Article: Elevation of plasma thrombomodulin level in diabetic patients with early diabetic nephropathy.
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    ABSTRACT: Thrombomodulin (TM) is a membrane protein in the vascular endothelium, and it plays an important role as a cofactor in the thrombin-catalyzed activation of protein C. It has also been found in human plasma; however, its clinical significance is not known. In this study, fasting plasma TM concentrations in 67 diabetic patients with different degrees of albuminuria (39 men aged 57 +/- 8 yr, 28 women aged 57 +/- 11 yr; means +/- SD) and 34 age- and sex-matched healthy subjects were investigated by use of a one-step sandwich enzyme immunoassay, a new method developed by H.I. and others. As a screening, the patients were divided into three groups according to the first morning urinary concentrations of albumin: group 1, less than 30 micrograms/ml (normoalbuminuria); group 2, 30-140 micrograms/ml (microalbuminuria); group 3, greater than 140 micrograms/ml (clinical nephropathy). There was no significant difference in plasma TM level between the control group (17.7 +/- 3.7 ng/ml, n = 34) and group 1 (16.9 +/- 3.4 ng/ml, n = 30); however, plasma TM concentrations in group 2 (22.8 +/- 3.4 ng/ml, n = 22) and group 3 (29.6 +/- 6.1 ng/ml, n = 15) increased significantly compared with those in the control group and group 1, respectively. As a further investigation, three timed overnight urine collections were made. The patients were allocated to three groups according to their rates of albumin excretion: group I, less than 20 micrograms/min (normoalbuminuria); group II, 20-200 micrograms/min (microalbuminuria); group III greater than 200 micrograms/min (clinical nephropathy).(ABSTRACT TRUNCATED AT 250 WORDS)
    Diabetes 09/1990; 39(8):983-8. · 8.29 Impact Factor
  • Article: Changes in the pancreatic A-, B- and D-cell populations during development of diabetes in spontaneously diabetic Chinese hamsters of the Asahikawa colony (CHAD).
    Y Iwashima, K Watanabe, I Makino
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    ABSTRACT: We investigated the pathological changes in pancreatic islets during the development of diabetes in spontaneously diabetic Chinese hamsters of the Asahikawa colony (CHAD), using morphometric analysis and specific immunocytochemical methods. We also investigated the relationships between changes in islet cell composition and the hormonal changes in the plasma and pancreas. Plasma and pancreatic insulin levels were significantly lower in diabetic hamsters than in pre-diabetic hamsters. However, plasma insulin levels in the pre-diabetic hamsters were significantly higher than those in the hamsters from the non-diabetic control strain, although the pancreatic insulin content in the pre-diabetics was significantly lower than that in the non-diabetics. Since even a severely diabetic CHAD is alive for many months after the onset of the disease without injections of insulin, its clinical course seems to be close to that of type 2 human diabetes. In contrast, plasma and pancreatic glucagon levels were significantly higher in diabetic hamsters than in non-diabetics and pre-diabetics. There were significantly positive correlations between plasma and pancreatic insulin, and plasma and pancreatic glucagon levels in CHAD (P less than 0.01). On the other hand, no significant differences in the pancreatic somatostatin content were found among the non-diabetics, pre-diabetics, and severe diabetics. Significant correlations were found between plasma and pancreatic hormone levels (except for somatostatin) and the advance of diabetes in CHAD (P less than 0.01). Morphometric analysis by planimeter revealed that islets in the severe diabetics were 25% smaller than in the pre-diabetics. Significantly less B-cell area within the diabetic islets was found when compared with the non-diabetic and pre-diabetic islets. Significantly larger A- and D-cell areas within the diabetic islets were found compared with the non-diabetic and pre-diabetic islets. There was a significant correlation between the areas of the three types of cell within the islets and the severity of diabetes (P less than 0.01). It is suggested, therefore, that the pancreatic islet function in CHAD is closely associated with the morphologic changes in islet endocrine cells. The elevation of plasma and pancreatic glucagon levels and the marked increase of the A-cell area within the islets from severely diabetic CHAD may reveal an absolute increase of A-cell numbers.
    Diabetes Research and Clinical Practice 04/1990; 8(3):201-14. · 2.75 Impact Factor
  • Article: Increased frequency of apolipoprotein epsilon 4 allele in type II diabetes with hypercholesterolemia.
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    ABSTRACT: The apolipoprotein E (apoE) phenotype and allele frequencies were examined in type II (non-insulin-dependent) diabetic patients with normolipidemia (n = 134) and hypercholesterolemia (type IIa hyperlipoproteinemia, n = 35; type IIb hyperlipoproteinemia, n = 42). The frequencies of apoE4-present phenotypes (apoE4/3, apoE4/4, and apoE4/2) were highest in the type IIa group (51.4%), followed by the type IIb group (38.1%) and the normolipidemic group (16.4%), respectively, whereas the frequency of the most common phenotype, apoE3/3, was lowest in the type IIa group (48.6%), followed by the type IIb group (61.9%) and the normolipidemic group (79.9%), respectively. There were significant differences in the apoE phenotype frequencies between the normolipidemic group and the type IIa and IIb groups. The frequency of the epsilon 4 allele was significantly higher in the type IIa (28.6%) and IIb (20.2%) groups than in the normolipidemic group (8.9%), whereas the frequency of the epsilon 3 allele was significantly lower in the type IIa (71.4%) and IIb (78.6%) groups than in the normolipidemic group (89.2%). The frequency of the epsilon 2 allele tended to be lower in diabetic patients with hypercholesterolemia. In addition, these frequencies were also examined in nondiabetic subjects (n = 59). The frequency of the epsilon 4 allele tended to be higher in hypercholesterolemic diabetic subjects (24.1%) than in hypercholesterolemic nondiabetic subjects (15.3%). These data suggest that diabetic patients with the epsilon 4 allele may be more susceptible to hypercholesterolemia than diabetic patients without the epsilon 4 allele and possibly nondiabetic subjects with the epsilon 4 allele, although the underlying mechanism is unknown.
    Diabetes 12/1987; 36(11):1301-6. · 8.29 Impact Factor
  • Article: Apolipoprotein E polymorphism and hyperlipemia in type II diabetics.
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    ABSTRACT: The relationship between apolipoprotein E (apoE) polymorphism and plasma lipids and hyperlipemia was investigated in 105 male type II diabetics and 111 male nondiabetics. ApoE phenotypes were determined by a one-dimensional rapid flat gel isoelectric focusing method as described previously. The apoE phenotype frequency in diabetics was similar to that in nondiabetics. The frequency of hyperlipemia was higher in diabetics (56.2%) than in nondiabetics (32.4%). It was highest in the apoE3/2 group of diabetics and nondiabetics, followed by the apoE4/3 and apoE3/3 groups in the order described, indicating that the susceptibility to hyperlipemia differs among the apoE phenotype groups. ApoE3/2 diabetics had significantly higher levels of apoE and very-low-density lipoprotein (VLDL) cholesterol (chol)/VLDL triglyceride (TG) ratios than apoE3/3 diabetics. The effects of diabetes mellitus on plasma lipid levels differed among the various apoE phenotype groups: i.e., plasma total chol and low-density lipoprotein (LDL) chol increased only in apoE3/2 and apoE4/3 diabetics and plasma high-density lipoprotein chol decreased only in apoE3/3 diabetics, as compared with the corresponding apoE phenotype groups of nondiabetics, whereas plasma TG, VLDL TG, and VLDL chol increased in the three apoE phenotype diabetics. Furthermore, an increase of apoEII:apoEIII ratio was observed in apoE3/3 diabetics, particularly in those with hypertriglyceridemia. This study has also shown that the increased apoEII:apoEIII ratio is due to increased sialation of apoE based on the study of sialidase digestion of apo VLDL.(ABSTRACT TRUNCATED AT 250 WORDS)
    Diabetes 01/1987; 35(12):1374-82. · 8.29 Impact Factor
  • Article: Apolipoprotein E phenotypes and plasma lipids in young and middle-aged subjects.
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    ABSTRACT: The relationship between apolipoprotein (apo) E phenotypes and the levels of plasma lipid, lipoprotein and apo E in young (mean, 21 years of age) and middle-aged (mean, 49 years of age) subjects was investigated. Apo E phenotypes were determined by a rapid flat gel isoelectric focusing method that we had developed previously. Young subjects with apo E3/2 and E4/3 had significantly higher levels of plasma triglyceride (TG), very low density lipoprotein (VLDL)-TG and VLDL-cholesterol than those with apo E3/3. Middle-aged subjects with apo E3/2 (54.5%) and E4/3 (39.1%) had higher frequency of hyperlipoproteinemia (mainly type IV) than those with apo E3/3 (25.8%). Furthermore, the middle-aged subjects with apo E3/2 had significantly higher levels of plasma TG, VLDL-TG and apo E, and significantly lower levels of plasma high density lipoprotein-cholesterol than those with apo E3/3. These results indicate that apo E phenotype E3/2 and E4/3 are associated with lipid abnormalities even in young subjects, which may be caused by impaired functions of apo E2 and E4.
    The Tohoku Journal of Experimental Medicine 02/1986; 148(1):25-34. · 1.24 Impact Factor