Biomedical subjects

L M Chuang

Publications and source records attributed to L M Chuang.

At least 73 records · Page 4Linked to original sources

PubMed1993

Insulin-stimulated oocyte maturation requires insulin receptor substrate 1 and interaction with the SH2 domains of phosphatidylinositol 3-kinase.

Xenopus oocytes from unprimed frogs possess insulin-like growth factor I (IGF-I) receptors but lack insulin and IGF-I receptor substrate 1 (IRS-1), the endogenous substrate of this kinase, and fail to show downstream responses to hormonal stimulation. Microinjection of recombinant IRS-1 protein enhances insulin-stimulated phosphatidylinositol (PtdIns) 3-kinase activity and restores the germinal vesicle breakdown response. Activation of PtdIns 3-kinase results from formation of a complex between phosphorylated IRS-1 and the p85 subunit of PtdIns 3-kinase. Microinjection of a phosphonopeptide containing a pYMXM motif with high affinity for the src homology 2 (SH2) domain of PtdIns 3-kinase p85 inhibits IRS-1 association with and activation of the PtdIns 3-kinase. Formation of the IRS-1-PtdIns 3-kinase complex and insulin-stimulated PtdIns 3-kinase activation are also inhibited by microinjection of a glutathione S-transferase fusion protein containing the SH2 domain of p85. This effect occurs in a concentration-dependent fashion and results in a parallel loss of hormone-stimulated oocyte maturation. These inhibitory effects are specific and are not mimicked by glutathione S-transferase fusion proteins expressing the SH2 domains of ras-GAP or phospholipase C gamma. Moreover, injection of the SH2 domains of p85, ras-GAP, and phospholipase C gamma do not interfere with progesterone-induced oocyte maturation. These data demonstrate that phosphorylation of IRS-1 plays an essential role in IGF-I and insulin signaling in oocyte maturation and that this effect occurs through interactions of the phosphorylated YMXM/YXXM motifs of IRS-1 with SH2 domains of PtdIns 3-kinase or some related molecules.

Amino Acid Sequence↗

PubMed1993

Human skeletal muscle insulin receptor substrate-1. Characterization of the cDNA, gene, and chromosomal localization.

Insulin receptor substrate-1 is a major substrate of insulin receptor Tyr kinase. We have now cloned the IRS-1 cDNA from human skeletal muscle, one of the most important target tissues of insulin action, localized and cloned the human IRS-1 gene, and studied the expression of the protein in Chinese hamster ovary cells. Human IRS-1 cDNA encodes a 1242 amino acid sequence that is 88% identical with rat liver IRS-1. The 14 potential Tyr phosphorylation sites include 6 Tyr-Met-X-Met motifs and 3 Tyr-X-X-Met motifs that are completely conserved in human IRS-1. Human IRS-1 has > 50 possible Ser/Thr phosphorylation sites and one potential ATP-binding site close to the NH2-terminal. The human IRS-1 gene contains the entire 5'-untranslated region and protein coding region in a single exon and was localized on chromosome 2 q36-37 by in situ hybridization. By Northern blot analysis, IRS-1 mRNA is rare and consists of two species of 6.9 and 6 kilobase. By using quantitative polymerase chain reaction after reverse transcription of total RNA from human fetal tissues, IRS-1 mRNA could be identified in all tissues. When human IRS-1 cDNA was expressed in Chinese hamster ovary cells, the protein migrated between 170,000-180,000 M(r) in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was rapidly Tyr phosphorylated upon insulin stimulation. Thus, IRS-1 is widely expressed and highly conserved across species and tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

Development of macrovascular diseases in NIDDM patients in northern Taiwan. A 4-yr follow-up study.

OBJECTIVE: To assess the development of macrovascular diseases and explore major associative factors in NIDDM. RESEARCH DESIGN AND METHODS: A total of 479 NIDDM patients > or = 40 yr of age were recruited from four community primary care health centers of northern Taiwan in July 1986 for a cohort study with a 4-yr follow-up. No patient required insulin therapy within 1 yr of diagnosis nor had a history of diabetic ketoacidosis. All were able to participate independently in the activities of daily living. BP and ECG were measured, and a structured questionnaire was asked of each patient. Venous blood after overnight fasting was collected every year to measure cholesterol, HDL cholesterol, plasma glucose, and HbA1c. RESULTS: The duration of diabetes was associated with the development of stroke with a relative risk of 1.063 for every 1-yr increment (P = 0.07). As for HVDs, the significant risk factors were serum cholesterol and HbA1c. For every 1-mg/dl increase in mean total cholesterol level, the relative risk of developing HVD increased 1.016-fold (P = 0.04). For every 1% increase in HbA1c, the relative risk of developing HVD increased 1.170-fold (P = 0.01). With regard to leg VDs, sex and cigarette smoking were significant risk factors. Women diabetic subjects had a higher relative risk than men. Cigarette smoking was significantly associated with leg VD with a relative risk of 6.9 for smokers compared with nonsmokers. The most significant risk factor for LVD was the total cholesterol level. For every 1-mg/dl increase in mean serum cholesterol level, the relative risk of LVD increased 1.013-fold. CONCLUSIONS: In the prevention of macrovascular diseases, effective intervention of the nondiabetic cardiovascular risk factors may be as important as or even more important than the good control of diabetes.

Adult↗

PubMed1992

The effect of oral buflomedil on microalbuminuria in non-insulin-dependent diabetic patients.

A total of 26 non-insulin-dependent diabetic patients were enrolled for a clinical study of the effect of buflomedil on microalbuminuria. None of the subjects had hypertension or macroproteinuria. Sixteen cases without previously known urinary albumin excretion rate (AER) were enrolled as experimental group. Buflomedil (Loftyl) was administered orally 600 mg daily in two divided doses in the experimental group while AER was determined 3 times with 3 weeks apart in all of the subjects. Ten cases with known microalbuminuria (greater than 8.55 micrograms/min) were enrolled as control group to check the extent of fluctuation in AER from collection to collection in the absence of urinary tract infection. Six of the experimental group showed AER of microalbuminuric level at the time before buflomedil administration and the remaining 10 patients were normoalbuminuric. The effects of buflomedil were compared between the microalbuminuric and normoalbuminuric subjects in the experimental group. The microalbuminuric group showed a significant decrease of AER from a baseline of 30.4 micrograms/min to 19.8 and 16.8 micrograms/min, respectively, after 3 and 6 weeks of treatment (P less than 0.05, Friedman two-way ANOVA). However, the respective values in the normoalbuminuric group were 5.3, 5.6 and 5.0 micrograms/min (P greater than 0.05, Friedman two-way ANOVA). The AER in the control group remained stationary during the study period (14.0, 12.1 and 11.4, respectively, Friedman two-way ANOVA, P greater than 0.05). These results suggest that buflomedil might be beneficial for the patients with microalbuminuria.

Adult↗

PubMed1992

Association of body build with non-insulin-dependent diabetes mellitus and hypertension among Chinese adults: a 4-year follow-up study.

Both cross-sectional and longitudinal studies on the association of body build with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension were conducted in Taiwan during the period 1986-1990. The cross-sectional study, was carried out in 1986 in Ta-An District of Taipei City and five rural areas evenly distributed in Taiwan Province. A total of 11,478 randomly selected subjects aged 40 years or over were surveyed. World Health Organization designations of diabetes and hypertension were followed. The longitudinal observation was made in 1990 for the cohort living in Taipei City who had neither diabetes nor hypertension in 1986. Of 2822 subjects, 1873 individuals participated in the follow-up study and 52 had died, giving a response rate of 67.6%. In comparison with Caucasian or Polynesian populations, Chinese adults have a much lower prevalence of obesity (body mass index [BMI] greater than 30 kg/m2). Univariate and multivariate analyses revealed both diabetes and hypertension increased as body build became heavier. The age-adjusted prevalence ratio and relative risk for the fourth quartile of BMI compared to the first quartile were 2.72 and 2.87, respectively, for diabetes as well as 2.96 and 2.24, respectively, for hypertension. Multiple logistic regression analyses revealed a slightly higher increase in prevalence of hypertension than that of diabetes for every 1 kg/m2 increase in BMI (1.16-fold and 1.12-fold, respectively), while a similar increase in BMI resulted in a slightly higher relative risk of diabetes than that of hypertension (1.14-fold and 1.11-fold, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Inhibitory effect of islet amyloid polypeptide of glucose-induced proinsulin biosynthesis in rat insulinoma cells.

Islet amyloid polypeptide (IAPP) has been recently identified as the principal constituent of amyloid deposits in pancreatic islets of patients with type 2 (non-insulin-dependent) diabetes mellitus and causes insulin resistance in some target cells. In addition, glucose-induced insulin secretion is inhibited by IAPP. We studied the effect of IAPP on proinsulin biosynthesis in rat insulinoma (RINr) cells. Glucose at concentrations of 0, 15, 30, 60, 100, and 300 mg/dl stimulated proinsulin biosynthesis in a dose-responsive and and actino-mycin D-inhibitable manner after 6 h of incubation. At a glucose concentration of 300 mg/dl, IAPP decreased the mean responses of proinsulin biosynthesis to 61.2 and 29% at concentrations of 0.1 and 1 microM, respectively, compared with the IAPP-free control. In conclusion, IAPP inhibits glucose-induced proinsulin biosynthesis in RINr cells. IAPP might play an important role in the pathogenesis of type 2 diabetes mellitus.

Amyloid↗

PubMed1992

Therapeutic effect of guar gum in patients with non-insulin-dependent diabetes mellitus.

Diets with a high-fiber content have been shown to produce some beneficial effects on metabolic factors in subjects with NIDDM. However, some controversies still exist. In this report, the long-term effect of guar gum (Guarina) on both glycemic and blood lipid profiles was assessed in a randomized, double-blind and cross-over study on 16 (seven male and nine female) subjects with NIDDM. Each subject received placebo (P) and Guarina (G) treatment for two eight-week periods separated by a four-week period to facilitate wash-out. Fasting plasma glucose levels showed significant improvement during G treatment but not during P treatment (151.7 +/- 7.9 vs 168.6 +/- 12.2 mg/dl, p less than 0.01 by paired Student's t test). Hemoglobin Alc levels decreased significantly during G treatment but not during P treatment (6.9 +/- 0.2 vs 7.2 +/- 0.8%, p less than 0.001). Fasting insulin concentrations also showed significant lowering during G treatment but not during P treatment (18.3 +/- 2.1 vs 23.1 +/- 2.9 U/ml, p less than 0.005). Other variables, including serum total cholesterol, triglyceride, HDLc, LDLc, sodium, potassium, chloride, magnesium and calcium levels showed no significant changes during G or P treatment. Ten out of the 16 patients (62.5%) suffered from side effects; these included abdominal cramps (one case), diarrhea (seven cases) and skin itching (one case). In conclusion, guar gum effectively lowers fasting plasma glucose and HbAlc levels in subjects with NIDDM. Hyperinsulinemia could also be ameliorated. The effectiveness and side effects of guar gum treatment should be cautiously evaluated in each NIDDM subject.

Adult↗

PubMed1992

Effect of tocopherol on platelet aggregation in non-insulin-dependent diabetes mellitus: ex vivo and in vitro studies.

Tocopherol has been shown to have antiplatelet effects in insulin-dependent diabetes mellitus. However, its antiplatelet effect in non-insulin-dependent diabetes mellitus (NIDDM) remains to be established. In this report, the antiplatelet effect of tocopherol was assessed in a randomized, double-blind and crossover study of 15 NIDDM subjects. Each subject received tocopherol (dl-alpha-tocopherol nicotinate, 200 mg, tid) and a placebo for two six-week treatment periods separated by a three-week period in between for wash-out. The mechanisms of the antiplatelet effect of tocopherol were also studied in vitro. A significant decrease in platelet reactivity was observed after tocopherol treatment as compared with the pretest, and the magnitude of the decrease during tocopherol treatment was significantly evident when compared with that of the placebo treatment, as assessed by collagen (5, 10 micrograms/mL)-induced platelet aggregation of whole blood. A dose-dependent reduction in both ADP-and collagen-induced platelet aggregation was observed with tocopherol from 0.1 to 3.0 mM in vitro. No corresponding changes in ATP secretion and thromboxane synthesis were observed. Tocopherol also significantly inhibited fibrinogen-induced aggregation of elastase-treated platelets at a concentration of 0.1 mM. We demonstrated that platelet aggregation of whole blood ex vivo, among 15 NIDDM subjects was suppressed in tocopherol treatment, so tocopherol may have an antiplatelet effect in NIDDM subjects. The inhibitory effect of the platelet aggregation of tocopherol may be partially accomplished through interference with fibrinogen binding towards its receptor.

Adult↗

PubMed1992

Bedtime intermediate-acting insulin in the treatment of secondary failure to oral hypoglycemic agents.

Low-dose bedtime insulin therapy in combination with oral hypoglycemic agents (OHAs) has become an alternative treatment for NIDDM subjects with secondary failure to OHA. To assess its clinical efficacy, patient compliance, and its possible side effects, 33 patients with secondary OHA failure were recruited in this study. All of the subjects had experienced poor glycemic control for at least six months on their maximal OHAs before the institution of the bedtime insulin injection. Monotard HM (human insulin zinc suspension) was given at an initial dose of 0.15-0.2 U/kg body weight and was adjusted thereafter. As a whole, low-dose bedtime insulin with OHAs improved glycemic control. According to the clinical response, 10 patients (30.3%) were graded as responders, 12 (36.4%) were partial responders, 10 (30.3%) were non-responders, and one (3%) discontinued insulin therapy. There was no difference in demographic features among these three groups of patients. During this period, eight (25%) cases experienced mild hypoglycemic symptoms. In conclusion, combination of OHAs with a low-dose bedtime insulin injection is an alternative therapy for NIDDM patients with OHA failure.

Diabetes Mellitus, Type 2↗

PubMed1992

Increase of blood glucose concentrations in diabetic patients with glucagon eyedrops.

Hypoglycemic crisis is a common occurrence in diabetic patients. In order to reverse the hypoglycemia, glucagon eyedrops at concentrations of 2.5%, 5.0%, and 7.5% were instilled to the eyes of diabetic patients who were fasted overnight. The glucagon eyedrops raised the blood glucose efficiently in a dose-dependent manner and peaked at 30 min after drug instillation. At 2.5%, glucagon raised the blood glucose 0.83 mmol.L-1 which exceeded the minimal requirement of 0.56 mmol.L-1 increase in blood glucose level at hypoglycemic crisis. At 5.0% and 7.5%, glucagon eyedrops increased the blood glucose level further to 1.76 and 1.91 mmol.L-1, respectively. These results indicate that glucagon can be delivered effectively through ocular route to raise the systemic blood glucose for the treatment of hypoglycemic crisis.

Adult↗

PubMed1991

Esterase D and retinoblastoma gene loci are tightly linked to Wilson's disease in Chinese pedigrees from Taiwan.

Wilson's disease (WD) is a rare autosomal recessive disorder and has been mapped to the long arm of chromosome 13 (q14.1). We have analyzed the segregation of esterase D (ESD) and retinoblastoma (RB) gene loci in ten families of Chinese WD subjects living in Taiwan. The polymorphic information content (PIC) for ESD and RB was 0.18 and 0.31, respectively. We confirmed a tight linkage between these loci and WD with a lod score of 3.33 by multipoint linkage analysis. The data from this limited number of pedigrees also suggested the following order: centromere-WD-RB-ESD or centromere-ESD-RB-WD. ESD in conjunction with RB polymorphism would be useful in prenatal and presymptomatic diagnosis, as well as in carrier detection in informative pedigrees.

Alleles↗

PubMed1991

Link between hypertension and diabetes mellitus epidemiological study of Chinese adults in Taiwan.

OBJECTIVE: To elucidate the relationship between hypertension and non-insulin-dependent diabetes. RESEARCH DESIGN AND METHODS: The study consisted of a random sample of adults aged greater than or equal to 40 yr from the Ta-An district of Taipei City and 5 of 12 villages of Taiwan province, which had established primary health-care centers since 1984. A total of 11,478 subjects were recruited into the survey with a response rate of 65.3 and 72%, respectively. Blood glucose and blood pressure levels were measured, and a structured questionnaire was given to each participant. Those identified as having diabetes received further blood tests for lipids and creatinine and were evaluated for vascular complications. RESULTS: The age- and sex-adjusted prevalence of hypertension among diabetic subjects was twice that of nondiabetic subjects (30.6 vs. 16.4%, P less than 0.0005). Hypertensive subjects had a higher prevalence of diabetes than normotensive subjects (10.2 vs. 4.9%, P less than 0.0005). Among hypertensive subjects, the prevalence of diabetes was 12.7% for those taking antihypertensive drugs and 9.1% for those not taking any drug (P less than 0.05). The prevalence of diabetes significantly increased as mean arterial pressure rose, whether the subjects were stratified by various factors. Multiple regression analysis, including sex, age, body mass index, and other risk factors as independent variables, also showed a significant association between diabetes and hypertension. CONCLUSIONS: The univariate and multivariate analyses revealed that there seemed to be a tight link between hypertension and non-insulin-dependent diabetes. Family history of diabetes, diabetes duration, diabetes regimen, control of blood glucose, and the presence of nephropathy, as attested by proteinuria, did not contribute to the risk of hypertension. Further studies are necessary to determine whether these two conditions are causally related.

Adult↗

PubMed1991

Lack of binding effect of insulin on RNA synthesis to isolated nuclei.

Insulin stimulates RNA synthesis in the human hepatoma cell line J5. The mechanisms of insulin action on nuclear functions are not fully understood. To assess the possible action of nuclear insulin binding on RNA synthesis, we studied the insulin action by an in vitro transcription system using the nuclei isolated from control cells and insulin-stimulated J5 cells. Insulin binding was done by ligand binding assay. RNA synthesis was also studied in the nuclei treated with insulin in vitro. We found that a large pool of low-affinity binding sites existed in the isolated nuclei preparation without site-to-site interactions. These data suggest that the majority of nuclear insulin binding sites are located inside the nuclear envelope. Nuclear RNA synthesis was stimulated by the insulin (about a 4-fold increase when compared to the control) added to intact cells but not to isolated nuclei. We conclude that insulin stimulates nuclear RNA synthesis via interaction with plasma membrane receptors.

Binding Sites↗

PubMed1991

Effect of treatment of borderline hypertension on microalbuminuria in non-insulin-dependent diabetes mellitus.

The advantage of treatment for borderline hypertension has been a debate. We studied two of the commonly used antihypertensive drugs, i.e., trichlormethiazide (Fluitran 2 mg/tab) and enalapril (Renitec 5 mg/tab) on urinary albumin excretion in seven NIDDM subjects with borderline hypertension, who had never been treated with antihypertensive drugs before entry into this study. The observation period was 2 months, and the treatment period was 6 months. Trichlormethiazide (1 tab qd) or enalapril (1 tab qd) were randomly assigned for the first 3 months and then patients were switched to the other drug for the following 3 months. During the treatment period, blood pressure, body weight, blood chemistry including renal function tests, and urinary albumin excretion rate were regularly followed up every 1 to 3 months. The results showed that both of the regimens significantly lowered blood pressure and the urinary albumin excretion rate [12.72 (2.56-25.95) micrograms/min at baseline, to 5.11 (3.0-13.73) micrograms/min during trichlormethiazide treatment and 4.96 (1.38-11.14) micrograms/min during enalapril treatment, p less than 0.008]. However, no significant difference was noted between the two drugs. The magnitude of change in the urinary albumin excretion rate did not correlate with the changes in blood pressure. Renal function, glycemic control, and lipid profiles did not change significantly during the treatment period. In conclusion, both trichlormethiazide and enalapril are effective in lowering the urinary albumin excretion rate in NIDDM subjects with borderline hypertension.

Aged↗

PubMed1990

Microalbuminuria and diabetic complications in Chinese non-insulin-dependent diabetic patients: a prospective study.

Urinary albumin excretion rate (AER) was monitored for periods of up to 3 years and 8 months with an ELISA method in 63 non-insulin-dependent diabetic Chinese subjects and was compared with 50 normal subjects. AER was 3.15 +/- 0.25 micrograms/min (M +/- SE) with a range of 0.27-8.40 micrograms/min for the normal subjects and 7.11 +/- 0.50 (2.11-19.45) micrograms/min for the diabetic subjects. The latter had significantly higher AER (P less than 0.0005). Age, sex, duration of diabetes, HbA1c and BMI did not correlate with AER in the diabetics. The presence of hypertension was found to be accompanied by an accelerated elevation of AER (5.96 +/- 1.58 vs 10.16 +/- 2.17 micrograms/min, at the beginning and at the end of the observation, respectively). Once hypertension became evident, control of blood pressure to a level comparable to that of the non-hypertensive group was not sufficient to halt the deterioration of urinary albumin excretion.

Age Factors↗

PubMed1990

Complete agenesis of the dorsal pancreas--a case report and review of the literature.

A case of agenesis of the dorsal pancreas associated with diabetes mellitus and dilated biliary trees was reported. Preoperative diagnosis was made by endoscopic retrograde cholangiopancreatography and computed tomography. Laparotomy revealed a normal head of the pancreas but complete agenesis of the body and tail. Biopsy specimens removed from the head showed normal pancreatic tissue but only fat tissue from the presumed body and tail. This anomaly has rarely been reported in the literature. A thorough review of the literature was made and consideration of differential diagnosis was discussed.

Cholangiopancreatography, Endoscopic Retrograde↗

PubMed1990

A comparison of newly and previously diagnosed diabetics in Taiwan.

Between 1985 and 1986, during a population survey of diabetes in 1 urban and 5 rural areas of Taiwan, a total of 11,478 adults aged 40 or older were screened. Capillary whole blood glucose was determined with a glucometer (Ames Co.) The diabetic criteria followed the WHO designations. From this survey, a comparison of 225 newly diagnosed and 383 previously diagnosed diabetics was conducted. Multiple regression analysis revealed a highly significant correlation for all diabetics with regard to age, body mass index, family history and hypertension, but no specific correlation to habitat. Mean fasting glucose levels in previously and newly diagnosed diabetics were 172 and 158 (males 158 vs 147 and females 184 vs 165) mg/dl, respectively, which suggest that treatment is apparently inadequate in this population. The prevalent rate (%) of retinopathy for previously and newly diagnosed diabetics was 45.2 and 28.3 (males 42.8 vs 33.3 and females 47.5 vs 24.8), respectively. The prevalence is as common as those reported in western countries. In conclusion, previously diagnosed diabetics had higher fasting glucose concentrations and prevalent rates of retinopathy than newly diagnosed diabetics, and these findings were particularly prominent in females.

Adult↗

PubMed1990

Continuous blood glucose monitoring with feedback-controlled glucose infusion during surgical management of insulinoma: report of a case.

Perioperative management of insulinoma may be facilitated by the use of a glucose-controlled insulin infusion system (GCIIS; Biostator System, Miles Laboratories Inc., Elkhart, Ind.). We monitored the blood glucose levels and glucose infusion rates before, during and after surgery in a 35-year-old woman with insulinoma. After an overnight fast, glucose was infused according to a preset program and maintained the blood glucose level at around 50 mg/dl. Depression of the blood glucose level and simultaneous elevation of the glucose infusion rate were noted when the tumor was massaged. A sharp decrease in the glucose infusion rate occurred almost immediately after removal of the tumor. It took about 4 minutes for the blood glucose to go up to a level of 90 mg/dl. These results demonstrate the usefulness of GCIIS not only in maintaining stationary blood glucose, but also in localizing the tumor and in providing evidence of complete removal of the tumor. When the infusion system is programmed appropriately, the glucose infusion rate, as compared to the blood glucose level, reacts more quickly and sensitively to sudden changes in insulin levels.

Adult↗