Biomedical subjects

C F Kwok

Publications and source records attributed to C F Kwok.

At least 37 records · Page 2Linked to original sources

PubMed1999

Octreotide effect on hypersecretion of growth hormone in a patient with fibrous dysplasia: a case report.

We report the case of a 17-year-old adolescent boy with polyostotic fibrous dysplasia and hypersecretion of growth hormone (GH). The fasting serum GH, insulin-like growth factor-I (IGF-I), alkaline phosphatase activity and osteocalcin levels were all elevated. The GH secretion was stimulated by thyrotropin-releasing hormone and was not suppressed by an oral glucose test. Magnetic resonance imaging of the sella turcica showed no abnormal findings. The patient was treated with octreotide, 100 micrograms subcutaneous injection three times a day for two weeks to observe the effects of octreotide on growth hormone secretion. GH and IGF-I secretions were suppressed by octreotide therapy, while alkaline phosphatase activity and osteocalcin secretion were partially suppressed. We suggest that the high bone turnover states in this patient may be attributed to both hypersecretion of growth hormone and the polyostotic fibrous dysplasia itself.

Adolescent↗

PubMed1998

4-Bromocrotonic acid enhances basal but inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes.

Inhibitors of fatty acid oxidation, 2-bromopalmitic acid (Br-C16) and 4-bromocrotonic acid (Br-C4) were examined for their effect on glucose transport in 3T3-L1 adipocytes. Whereas Br-C16 was without effect, Br-C4 augmented basal but inhibited insulin-stimulated 2-deoxyglucose uptake in a dose- and time-dependent manner. Immunoblot analysis indicated that following Br-C4 pretreatment, the content of GLUT1 in plasma membranes was increased whereas insulin-induced translocation of GLUT4 was greatly eliminated. The total cellular amount of GLUT1 or GLUT4, on the other hand, was not altered. Thus these results seem to suggest that Br-C4 has opposite effect on basal and insulin-stimulated glucose transport by a mechanism other than its inhibition of fatty acid oxidation. The translocation processes for both GLUT1 and GLUT4 transporters appears to be altered.

3T3 Cells↗

PubMed1998

Evidence that endothelin-1 (ET-1) inhibits insulin-stimulated glucose uptake in rat adipocytes mainly through ETA receptors.

The specificity of endothelin (ET) receptors involved in the inhibition of insulin-stimulated glucose uptake (ISGU) in rat adipocytes was investigated. Adipocytes were isolated from the epididymal fat pads of Sprague-Dawley rats. To determine receptor subtypes, we used three ET isopeptides, ET-1 and ET-2, both of which are nonselective agonists, and ET-3, a selective agonist for ETC receptors, to displace [125I]ET-1 binding from the fat cells. The efficiency of displacement was ET-1 > ET-2 >> ET-3, indicating that the primary receptors involved belonged to the ETA subtype. At an equal concentration of 1 micromol/L, BQ-610, a selective ETA antagonist, displaced [125I]ET-1 from binding to fat cells, whereas IRL-1038, a selective ETB antagonist, did not. Using [3H]2-deoxy-D-1-glucose ([3H]2-DG) as a tracer in studies of glucose uptake, we found that equimolar BQ-610 completely reversed the inhibitory effect of ET-1 on ISGU, whereas IRL-1038 was ineffective. Northern blot analysis of adipocyte receptors showed abundant mRNA for ETA, but no ETB subtype. These results clearly demonstrate that ETA is the predominant receptor in rat adipocytes.

Adipocytes↗

PubMed1998

Technical and clinical evaluation of an electrochemistry glucose meter: experience in a diabetes center.

The Sensorex (Metertech, Taipei, Taiwan), an electrochemical blood glucose meter, is designed for self-monitoring of blood glucose (BG) concentrations in capillary blood through the use of an electrochemical test strip. The intra-assay coefficients of variation of Sensorex were 5.2, 5.4, and 4.7% at BG levels of 46, 154 and 302 mg/dl respectively. The BG concentrations tested by Sensorex were correlated well with those by YSI method (r approximately/= 0.85, P < 0.0001). The intraclass correlation coefficients (rI) between the results obtained by Sensorex and YSI were 0.84 in capillary blood and 0.69 in venous whole blood, which indicated good agreement between both methods. The Sensorex was evaluated by error grid analysis and revealed 'acceptance' results. In field test, the Sensorex results obtained by lay users were in concordance with those by trained technicians (rI = 0.87). Our data show that the Sensorex glucometer is reliable and easy to use. We also demonstrate a practical clinical approach for the evaluation of a novel SMBG system.

Adolescent↗

PubMed1998

Steroid cell tumors of the ovary: clinical, ultrasonic, and MRI diagnosis--a case report.

Steroid cell tumors of the ovary are rare sex-cord neoplasms which account for less than 0.1% of all ovarian tumors. They have been divided into two subtypes according to their cell of origin as follows: stromal luteoma, and Leydig cell tumors, and a third subtype with lineage unknown is a steroid cell tumor, not otherwise specified (NOS). The clinical presentation may take many forms, including pain, abdominal distention and bloating, but perhaps the most interesting and noticeable presentations are those related to the hormonal activity and virilizing properties of the tumor. No radiological features of the steroid cell tumor, NOS have been presented in the literature. This report presents the MRI and ultrasonographic findings of a patient having steroid cell tumor, NOS, of the right ovary with metastasis to the uterus.

Female↗

PubMed1998

Overexpression of vascular endothelin-1 and endothelin-A receptors in a fructose-induced hypertensive rat model.

OBJECTIVE: To examine the temporal relationship between hyperinsulinemia and hypertension in the fructose-hypertensive rat model and to study the function of endothelin-1 (ET-1) in fructose-induced hypertension. DESIGN: Since ET-1 induces insulin resistance in conscious rats, we tested the hypothesis that both hyperinsulinemia and hypertension developed in the fructose-hypertensive rat model might be the sequelae of an elevated tissue content of ET-1 and ET(A) receptors. MATERIALS AND METHODS: Systolic hypertension was induced within 3 weeks in male Sprague-Dawley rats fed on a fructose-rich diet. After continual monitoring of blood pressure and plasma insulin concentrations, the animals were killed at the end of experiment to determine plasma levels of ET-1, the contractile response of aortic rings to ET-1, and ET-1 and ET(A) receptor gene expressions. In a separate experiment, BQ-610 was administered to lower the effect of ET-1 in rats with fructose-induced hypertension. RESULTS: Compared with control rats given normal chow, the fructose-fed rats developed systolic hypertension after 3 weeks of the diet (127+/-3.7 versus 110+/-5.5 mmHg, P < 0.01) and hyperinsulinemia both before (1 07.1+/-32.5 versus 48.5+/-14.3 pmol/l, P < 0.005) and after (96.6+/-63.7 versus 50.4+/-5.6 pmol/l, P< 0.05) they became hypertensive. Although plasma ET-1 levels did not differ between the rat groups, aortic ring contraction-concentration curves, indicating vessel contractility in response to ET-1, were significantly greater in these rats than in controls (F1,72 = 12.34, P< 0.00077). Messenger RNA extracted from the tail arteries and blotted with both ET-1 and ET(A) probes showed that fructose-fed rats had greater ET-1 and ET(A)-receptor gene expression than control rats. Concomitant administration of BQ-610 to rats fed on a fructose diet significantly reduced the hypertension. Conclusions These findings suggest that elevated vascular expression of ET-1 and ET(A) receptor genes may mediate the development of hypertension and hyperinsulinemia in rats fed a fructose-rich diet

Animals↗

PubMed1998

Trilinolein inhibits the adhesion of neutrophils to endothelial cells.

1. Trilinolein is a triacylglycerol with linoleic acid as the only type of fatty acid in all three esterified positions of glycerol. It was recently reported to have a myocardial protective effect in coronary ligated rats. We now study its effect on the adhesion of human neutrophils to cultured bovine endothelial cells. 2. Pretreatment of an endothelial monolayer with trilinolein at concentrations ranging from 10(-10) to 10(-6) mol/L significantly inhibited neutrophil adhesion to endothelial cells. Trilinolein was less potent than sodium nitroprusside in inhibiting neutrophil adhesion. 3. The inhibitory effect of trilinolein was antagonized by methylene blue and N(G)-nitro-L-arginine methyl ester. The inhibitory effect of trilinolein was not mediated through linoleic acid because linoleic acid did not inhibit neutrophil adhesion. 4. Pretreatment of neutrophils with trilinolein did not reduce neutrophil adhesion. However, in neutrophils activated with N-formyl-methionyl-leucyl-phenylalanine, trilinolein inhibited the neutrophil adhesion to endothelial cells. 5. We conclude that trilinolein inhibits neutrophil adhesion to the endothelial monolayer by stimulating the nitric oxide and cyclic GMP pathways in endothelial cells. It may also inhibit neutrophil adhesion by scavenging free radicals. The inhibitory effect of trilinolein on neutrophil adhesion may play a role in its myocardial protective activity.

Animals↗

PubMed1997

Amelioration of insulin resistance and hypertension in a fructose-fed rat model with fish oil supplementation.

In type II diabetic patients, one can detect several pathologic changes including insulin resistance and hypertension. Sprague-Dawley rats fed a fructose-rich diet (group F) exhibited these characteristic abnormalities within 2 weeks and were an excellent laboratory animal model for research on insulin action and development of hypertension. Since fish oils containing omega-3 fatty acids have a beneficial effect in preventing atherosclerotic diseases, we performed repeated experiments to test the effects of fish oil supplementation in group F rats. Compared with control rats on a normal diet (group C), group F consistently developed hypertriglyceridemia without elevated plasma free fatty acid (FFA), fasting hyperinsulinemia together with fasting hyperglycemia (insulin resistance syndrome), and systolic hypertension within 3 weeks. Insulin-stimulated glucose uptake and insulin binding of adipocytes were significantly reduced. Rats fed the same high-fructose diet but supplemented with fish oil (group O) had alleviation of all of these metabolic defects and a normalized insulin sensitivity and blood pressure. beta-Cell function as shown by plasma glucose and insulin responses to oral glucose remained intact in group F and group O. The plasma endothelin-1 (ET-1) level and ET-1 binding to adipocytes were not different among the three groups. Based on these results, we suggest that dietary high fructose induced hypertriglyceridemia and insulin resistance with normal islet function, and that the induced hypertension was not associated with plasma ET-1 abnormalities and was probably caused by other undefined pathologic changes that can be prevented by dietary omega-3 fatty acids.

Adipocytes↗

PubMed1997

Acipimox attenuates hypertriglyceridemia in dyslipidemic noninsulin dependent diabetes mellitus patients without perturbation of insulin sensitivity and glycemic control.

Hyperlipidemia, hypertriglyceridemia in particular, is a common feature in patients with noninsulin dependent diabetes mellitus (NIDDM) and may associate with insulin insensitivity. Acipimox, being widely prescribed for treating hypertriglyceridemia, is also used in NIDDM patients for their dyslipidemia. In the present study, we evaluated the effect of acipimox in Chinese NIDDM patients with hypertriglyceridemia. A total of 16 patients enrolled in a double-blind, randomized, placebo-controlled and two-period crossover study. After an 8 week run-in period, patients were randomly assigned into two groups receiving either acipimox (250 mg, twice daily) or placebo treatment. A total of 12 weeks later, these two groups switched their treatment for an additional 12 weeks. Blood samples were collected at the end of the run-in period and then at 4-week intervals in the whole study for lipid profile. A modified insulin suppression test was performed at the ends of the run-in period, 12-week and 24-week treatment to assess changes in insulin sensitivity. Our results showed that acipimox significantly lowered serum total triglyceride while compared to those by placebo. However, no difference was observed in serum non-esterified fatty acid, low-density lipoprotein cholesterol, total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C) and HDL-C/ TC ratio between the two groups. Furthermore, glycemic indices and insulin sensitivity were similar during the base-line, placebo or acipimox periods. Taken together, our data suggest that acipimox significantly lowered TG without perturbation of insulin sensitivity in hypertriglyceridemic NIDDM patients.

Adult↗

PubMed1997

Growth hormone (GH) replacement reduces total body fat and normalizes insulin sensitivity in GH-deficient adults: a report of one-year clinical experience.

The effects of GH replacement on body fat composition and insulin sensitivity were assessed in GH-deficient adults. The patients were randomized into a double-blind, placebo-controlled study of human recombinant GH replacement therapy for 6 months (period 1), followed by an open phase of GH for another 6 months (period 2). Anthropometric variables, body fat composition (fat %), and biochemical parameters were measured during the trial. Measurements of in vivo insulin sensitivity were carried out at the commencement of the study and on completion of the trial by modified insulin suppression test. The modified insulin suppression test was performed both in the morning (AM) and in the afternoon (PM) to further evaluate the PM-AM steady-state plasma glucose (SSPG) pattern. We found that the GH-deficient adults had more body fat and were insulin resistant. Significant reduction in fat % and total body fat mass was found in the active arm of period 1 without alteration of body weight. Besides, we demonstrated, for the first time, the GH replacement for 6 months did not alter the insulin sensitivity, but replacement for a longer period (12 months) normalized not only the AM SSPG level but also the PM-AM SSPG pattern. We also found a positive correlation between SSPG (regardless of AM vs. PM) and fat % and total body fat mass. In conclusion, normalization of insulin sensitivity in GH-deficient adults after replacement of GH may be related to the reduction of total body fat.

Adipose Tissue↗

PubMed1996

Endothelin-1 induces insulin resistance in conscious rats.

Since endothelin-1 (ET-1) might regulate insulin secretion and glucose metabolism, we carried out experiments to study the effect of ET-1 in conscious rats by injecting ET-1 (0.5 or 1.0 microgram/100 g body weight, i.p.) and examining the plasma glucose (PG) and insulin (PI) concentrations and PG/PI ratios continuously for 3 hours after the injection. Compared to the saline controls, ET-1 increased PG and PG/ P1 ratios in a dose-dependent manner. Oral glucose tolerance test (OGTT) performed at 30 min after the injection showed that PG levels stayed significantly higher in rats preinjected with ET-1 than rats with saline injection, although the change in PI levels was not different. Simultaneous infusion of glucose and insulin to somatostatin-primed rats with ET-1 or saline injection resulted in significantly higher steady state plasma glucose (SSPG) levels and SSPG/PI ratios in rats injected with ET-1 than control rats with saline. These results unequivocally indicated that intraperitoneally administered ET-1 induces insulin resistance in conscious rats.

Animals↗

PubMed1996

Heterogeneous responses to the long-term treatment of active acromegaly with octreotide.

To study GH response to the long-acting somatostatin analogue, we treated 11 actively acromegalic patients with octreotide (Sandostatin), 100 micrograms, sc, tid, for six months. Their endocrinological outcomes and clinical improvements varied. The 11-h GH secretory profiles on pretreatment day confirmed the hypersecretion of GH in all patients. Three hours after the first dose of octreotide, serum GH declined rapidly to levels below 5 ng/ml in all but two patients who failed to normalize their serum GH. In spite of the subsequent doses, there was no further suppression in serum GH. Drug resistance with GH rebound developed in some patients after three months of continued treatment. The paradoxical serum GH rises in response to oral glucose or iv TRH detected before the treatment in all patients attenuated or disappeared after the 6-month octreotide therapy; an exceptional case was one of the above-mentioned two patients, whose serum GH was stimulated more than before by glucose and TRH at the end of therapy. Serum insulin-like growth factor I (IGF-I) levels of all patients showed a significant reduction after 6-month treatment, but their mean values remained abnormally high. There were no intolerable adverse side effects; some patients, however, experienced pain at the injection site, passage of loose stool, and incidence of new gall stone or intrahepatic lesions on octreotide therapy. We concluded that octreotide was a useful long-term adjunctive therapeutic agent for patients with active acromegaly, but that a high degree of response heterogeneity including total refractoriness would be expected.

Acromegaly↗

PubMed1996

Lovastatin lowers serum cholesterol levels in non-insulin-dependent diabetes mellitus patients without altering their insulin sensitivity.

BACKGROUND: Lovastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in the treatment of hypercholesterolemia. It is also applied to dyslipidemia in patients with diabetes mellitus. The influence of lovastatin on insulin sensitivity was evaluated in twelve Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients with hypercholesterolemia. METHODS: This double-blind, randomized, placebo-controlled, and two-period cross-over experiment enrolled 12 patients. After a run-in period of two months, the patients were randomized into 2 groups to receive either lovastatin (20 mg once daily) or placebo treatment. Eight weeks later, two groups of patients exchanged their treatment for another 8 weeks. Blood samples were collected at the end of the run-in period and at 4-week intervals during the study to observe serum lipid profiles. A modified insulin suppression test was made to assess insulin sensitivity three times: at the end of run-in period, in week 8 and week 16, respectively. Wilcoxon signed rank test was used for analysis of statistical significance of the difference between lovastatin and placebo treatments. RESULTS: As compared with the placebo, lovastatin reduced serum total cholesterol (TC) levels significantly. Serum total triglyceride (TG) concentrations decreased slightly by lovastatin. The ratio of TC to high density lipoprotein-cholesterol (HDL-C) also decreased significantly in lovastatin period. No difference was found in serum apolipoprotein A1 levels. A significant reduction of serum apolipoprotein B concentrations was also noted in lovastatin period. No difference in glycemic indices and insulin sensitivity was observed in the base-line, placebo or lovastatin periods. CONCLUSIONS: The results demonstrated that lovastatin significantly lowered the serum TC levels without perturbation of insulin sensitivity in hypercholesterolemic NIDDM patients.

Aged↗

PubMed1994

Endothelin-1 inhibits insulin-stimulated glucose uptake in isolated rat adipocytes.

A single class of high affinity endothelin-1 (ET-1) binding sites with an apparent Kd of 350 pM and a binding capacity of 69,000 sites/cell was found in isolated rat adipocytes. Whereas ET-1 had no effect on basal glucose uptake, it inhibited insulin-stimulated glucose uptake in both a dose- and time-dependent manner. Insulin binding, however, was not altered. Thus, the present study demonstrates the presence of ET-1 receptor in isolated rat adipocytes and the inhibition of insulin-stimulated glucose uptake by ET-1 via a post-receptor mechanism.

Adipocytes↗

PubMed1994

The effects of in vitro and in vivo exposure to insulin upon prostaglandin E1 stimulation of platelet adenylate cyclase activity in healthy subjects.

Insulin treatment of platelets is associated with increased prostaglandin E1-stimulated adenylyl cyclase activity and decreased platelet aggregation. Because non-insulin dependent (Type II) diabetes mellitus is associated with hyperinsulinemia, we sought to determine the effect of insulin treatment in vivo and in vitro upon stimulation of platelet adenylyl cyclase by prostaglandin E1. Incubation of platelet-rich plasma obtained from normal subjects with 2 microM prostaglandin E1 resulted in a 16-fold increase in cAMP accumulation. Pre-incubation of platelet-rich plasma with 0.7 nM insulin resulted in a 62% increase in prostaglandin E1 (2 microM)-stimulated cAMP accumulation (p < 0.005). Pretreatment of platelets with cholera toxin prior to incubation with insulin had no effect on subsequent prostaglandin E1-stimulated cAMP accumulation. By contrast, pretreatment of platelets with pertussis toxin prior to incubation with insulin resulted in a nearly 2-fold increase in prostaglandin E1-stimulated cAMP accumulation (p < 0.005). To determine whether platelets exposed in vivo to elevated concentrations of insulin would show similar responses, we isolated platelet-rich plasma from subjects before and after a 120 minute euglycemic clamp study in which insulin was infused (40 mU m-2min-1) intravenously. Patients who underwent the euglycemic clamp study achieved steady state serum levels on insulin of 0.70 +/- 0.19 pmol/ml. Platelets obtained after insulin infusion had a 65% increase in prostaglandin E1-stimulated cAMP. Our results indicate that serum levels of insulin that are common in patients with type II diabetes mellitus can increase the sensitivity of platelet adenylyl cyclase to stimulation by prostaglandin E1.

Adenylate Cyclase Toxin↗

PubMed1993

Insulin-like growth factor-I receptor increases in aortic endothelial cells from diabetic rats.

Endothelial cells are likely to play an important role in the development of diabetic vascular diseases, since they are exposed directly to the abnormal circulating metabolites of diabetes and may be easily damaged early in the natural course of vascular complications. In this study, aortic endothelial cells were cultured from diabetic BB rats. Their binding and internalization of insulin-like growth factor-I (IGF-I) were measured. IGF-I binding was higher in cells of diabetic rats than of control rats at both 37 degrees C (4.5% +/- 1.6% v 2.74% +/- 0.9% per mg protein, P < .05) and 4 degrees C (20.6% +/- 5.6% v 13.7% +/- 4.6% per mg protein, P < .01). Internalization of IGF-I also increased (1.62% +/- 0.2% v 0.74% +/- 0.15% of total count at 37 degrees C after 60 minutes, P < .05). Cross-linking studies showed that in cells from diabetic rats, the major band of 140 kd corresponding to the alpha-subunit of the IGF-I receptor increased in density by 50% compared with those from control rats. The IGF-I-stimulated tyrosine kinase activity (TKA) of partially purified receptor from cells of diabetic rats, measured using poly-glu-tyr as substrate, was normal. Since the biological effects of IGF-I are initiated by its binding to the IGF-I receptor, which is able to transduce mitogenic and metabolic signals, our results support the hypothesis that the IGF-I receptor is involved in the development of diabetic vascular complications.

Affinity Labels↗

PubMed1992

Insulin-pen: preliminary report on its use for multiple injection regiment in insulin-dependent diabetic patients.

Insulin pens are pen-like devices for multiple injection of insulin. They can cut down the equipment necessary for a multidose regimen and thus make the therapy more convenient and flexible to help improve daily-life quality. It is of interest for us to known whether the average diabetic patients are motivated to achieve better metabolic control by means of insulin-pens. Seven insulin-dependent diabetic patients (male: 3, female: 4, age: 21-34 years) from the Veterans General Hospital participated in the study. None of them had diabetic proliferative retinopathy or proteinuria. They are initially treated with twice daily injection of mixtures of short- and intermediate-acting insulin (run-in period, 8 weeks). A multi-dose regimen with three premeal injections of short-acting insulin with insulin-pen plus one injection of long-acting insulin at bedtime was then used during the study period (12 weeks). Improved in metabolic control as assessed by HbAlc (7.6 +/- 0.9 vs 6.9 +/- 0.8%) and mean blood glucose (175.2 +/- 34 vs 152.3 +/- 28.1 mg/dl) in all patients was found. The frequency and severity of hypoglycemic episodes were not changed. In addition, all patients chose to continue multiple injection using insulin-pen, indicating a high acceptability of such device.

Adult↗

PubMed1992

Metabolic control and B cell function in patients with diabetes mellitus secondary to chronic pancreatitis.

To investigate the relationship between metabolic control and beta cell functions in chronic pancreatitis, 30 patients were selected for study, including 10 with diabetes mellitus in insulin-dependent state (group 1, Mean age 37.6), 10 with diabetes mellitus in non-insulin-dependent state (group 2, Mean age 47.8), and 10 with normal fasting glucose levels (group 3, Mean age 42.1). Each patient received urine routine, stool fat, renal function, biochemical study such as: serum lipid and glycosylated hemoglobin, eye fundi and X-ray examinations. Beta cell function was measured by C-peptide concentration six minutes after intravenous infusion of 1 mg glucagon. The results showed that the glycosylated hemoglobin concentrations were higher in group 1 than in group 2 or 3 patients (P less than 0.05), and were higher in group 2 than in group 3 patients (P less than 0.001) as well. The cholesterol and triglyceride levels were not significantly different among three groups. Furthermore, eight and two of group 1 and 2 patients manifested pancreatic calcification on abdomen X-ray examination (P less than 0.05). All and eight of group 1 and 2 patients received insulin injection respectively. In addition, group 1 patients were more likely to develop steatorrhea, other associated diseases and uncontrolled plasma glucose levels as compared with group 2 patients. In conclusion, insulin-dependent pancreatic diabetics had more advanced disease process and were therefore more likely to get other associated diseases than noninsulin-dependent pancreatic diabetics.

Adult↗