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Biomedical subjects

M H Tan

Publications and source records attributed to M H Tan.

At least 109 records · Page 6Linked to original sources

Effects of exercise on insulin binding and glucose metabolism in muscle.

To elucidate the mechanism of enhanced insulin sensitivity by muscle after exercise, we studied insulin binding, 2-deoxy-D-[1-14C]glucose (2-DOG) uptake and [5-3H]glucose utilization in glycolysis and glycogenesis in soleus and extensor digitorum longus (EDL) muscles of mice after 60 min of treadmill exercise. In the soleus, glycogenesis was increased after exercise (P less than 0.05) and remained sensitive to the action of insulin. Postexercise insulin-stimulated glycolysis was also increased in the soleus (P less than 0.05). In the EDL, glycogenesis was increased after exercise (P less than 0.05). However, this was already maximal in the absence of insulin and was not further stimulated by insulin (0.1-4 nM). The disposal of glucose occurred primarily via the glycolytic pathway (greater than 60%) in the soleus and EDL at rest and after exercise. The uptake of 2-DOG uptake was not altered in the soleus after exercise (4 h incubation at 18 degrees C). However, with 1-h incubations at 37 degrees C, a marked increase in 2-DOG uptake after exercise was observed in the soleus (P less than 0.05) in the absence (0 nM) and presence of insulin (0.2-4 nM) (P less than 0.05). A similar postexercise increase in 2-DOG uptake occurred in EDL. Despite the marked increase in glucose uptake and metabolism, no changes in insulin binding were apparent in either EDL or soleus at 37 degrees C or 18 degrees C. This study shows that the postexercise increase of glucose disposal does not appear to be directly attributable to increments in insulin binding to slow-twitch and fast-twitch muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Muscle glycogen repletion after exercise in trained normal and diabetic rats.

We hypothesize that training results in a faster and greater repletion of glycogen in skeletal muscles of normal and diabetic rats. Normal male Sprague-Dawley rats (100-140 g) were divided into two groups--one to train by treadmill running for 10 wk and the other to remain sedentary. Forty-eight hours after the last training session the rats of both groups were exercised to exhaustion. One subgroup of each was fed oral glucose (3 g/kg) at exhaustion and killed 60 min later. The other was killed at exhaustion. The glycogen concentration of soleus, plantaris, and red and white gastrocnemius was determined in all rats. The trained group had higher glycogen levels after glucose feeding in all muscles (P less than 0.002) and repleted their muscle glycogen more rapidly (P less than 0.05). However, in diabetic rats (45 mg streptozotocin/kg body wt) the trained and sedentary rats have similar glycogen levels and glycogen repletion rates in all muscles. Compared with the normal trained rats, the diabetic trained rats had slower glycogen repletion rates (P less than 0.05).

Animals↗

Diabetic amputees in Singapore.

We studied the clinical features of 262 consecutive patients who had 289 limb amputations in the University Department of Orthopaedics, Singapore General Hospital from January, 1978 to June, 1980. Of these, 171 (59.2%) were done for diabetic complications, 43 (14.9%) for trauma and 27 (9.3%) for atherosclerosis. The mean age of the three groups were 65 +/- 10 (S.D.), 32 +/- 17, and 75 +/- 8 years respectively. The indications for amputation in diabetics were gangrene (36%), ulcer (25%), infection (14%), gangrene and ulcer (11%), gangrene and infection (8.2%), and ulcer and infection (6%). The majority of diabetics were treated with oral agents (80.2%) and diet (6.4%), with 13.4% on insulin. Most patients had their diabetes for less than ten years-38.6% less than five years and 30.7% six-ten years. The mean known duration of the lesion was 1.13 +/- 1.42 months, with 38.7% less than one week. To determine the prevalence of peripheral vascular disease in diabetics admitted for amputation, the ankle/arm systolic BP ratio at rest and post-exercise were determined. In the affected leg, 16/19 patients had decreased ankle/arm systolic BP ratio. In another study, 23/26 diabetic amputees had decreased ankle/arm systolic BP ratio in the remaining leg. These data suggest that diabetes is the most common indication for amputation in this study. Most of these patients are Type II diabetics and have peripheral vascular disease.

Adult↗

Increased lipoprotein-remnant formation in chronic renal failure.

Since accelerated atherosclerosis may be induced by excess circulating remnants of triglyceride-rich lipoprotein catabolism, we looked for evidence of remnant particle accumulation in the lipoproteins of 11 patients on long-term dialysis. We found several abnormalities in lipoprotein protein and lipids: enrichment of intermediate-density lipoproteins (ILD) and low-density lipoproteins (LDL) with triglyceride; the presence of apoprotein B48 (a "marker" for intestinal lipoproteins) in very-low-density lipoproteins (VLDL); an increased concentration of apoprotein AIV (a protein related to chylomicron transport); the presence of AIV in VLDL, IDL, and LDL; and the presence in LDL of apoproteins C and E (proteins not normally found in LDL). These findings strongly suggest accumulation of remnants of triglyceride-rich lipoproteins in patients with chronic renal failure who are undergoing peritoneal dialysis or hemodialysis, and may explain in part the increased incidence of coronary deaths among these patients.

Adult↗

Physical training in diabetic rats: effect on glucose tolerance and serum lipids.

The effect of 10 wk of treadmill training on glucose tolerance, serum lipids, tissue lipoprotein lipase (LPL) activities, and triglyceride secretion rates (TGSR) were studied in normal and diabetic rats. Training had little effect on the glucose tolerance of the normal rats but ameliorated the deterioration of glucose intolerance seen in the sedentary diabetic rats. Trained diabetic and normal rats had lower serum triglycerides than their sedentary counterparts [diabetic 34 +/- 5 vs. 61 +/- 4 (means +/- SE); normal 34 +/- 3 vs. 50 +/- 3 mg/dl]. This hypotriglyceridemic effect was associated with a reduction in the TGSR in the trained rats (diabetics 0.34 +/- 0.05 vs. 0.51 +/- 0.02; normal 0.48 +/- 0.05 vs. 0.53 +/- 0.04 mg/min). There were no differences in the tissue LPL activities (soleus, gastrocnemius, epididymal fat, and heart) between the trained and sedentary rats in both groups. Training also did not affect the serum cholesterol and the high-density lipoprotein cholesterol levels in both groups of rats.

Animals↗

Continuous-flow enzymatic determination of high-density lipoprotein cholesterol.

A simple, sensitive, and precise continuous-flow (Technicon Auto Analyser II) method using enzymic reagents to measure high-density lipoprotein (HDL) cholesterol in the supernatant of serum treated with heparin-manganese reagent is described. 1. The sensitivity of the system was improved by increasing the flow rates of both sample and re-sample manifold lines to 0.23 ml/min. This allowed a recorder full-scale deflection equivalent to 840 mg cholesterol per litre, and permitted a precise determination of cholesterol in the 200-600 mg/l range. 2. Interaction between Mn++ and the enyzmic reagents caused false elevations of the peak plateau on the chart readings, especially when 2M MnCl2 was used. Addition of disodium ethylene-diaminetetra acetate (8 mmol/L) to the enzyme reagent eliminated the spike-like interference in the recorder tracings, and permitted more accurate chart readings. 3. The heparin-Mn++ reagents contributed to the measured HDL-cholesterol. Use of a saline blank improved precision. 4. The inter-assay variation was determined by analysing (n = 26) 2 quality control serum pools: X1 = 362 +/- 11.5 mg/l (CV = 3.18%) and X2 = 252 +/- 14.4 mg/l (CV = 5.74%).

Autoanalysis↗

Insulin binding and glucose uptake differences in rodent skeletal muscles.

Insulin binding and 2-deoxy-d-glucose uptake were compared in the soleus, plantaris, and extensor digitorum longus (EDL) muscles, in vitro, since the known biochemical profile of the soleus differs markedly from the other two. The present study showed that insulin binding increased in all three muscles with increasing concentrations of insulin in the range of 0.2-30 nM. However, the increase in binding of insulin to soleus at each insulin concentration exceeded that observed in the other two muscles (P less than 0.05). Differences between the plantaris and EDL were not significant. The quantity of insulin bound at each concentration also increased more rapidly in the soleus than in either the plantaris (P less than 0.05) or EDL (P less than 0.05). Basal and insulin-stimulated uptake of 2-deoxy-d-glucose was also greater in the soleus than in the other muscles (P less than 0.05). Maximal 2-deoxy-d-glucose uptake occurred at 1 nM insulin in each of the three muscles. These results indicate that in metabolically distinct types of skeletal muscles glucose uptake can differ markedly, and this is related to differences in the insulin binding capacities of these muscles.

Animals↗

Dietary therapy of hyperlipoproteinemias: new understandings.

Diet is the common denominator in the treatment of hyperlipidemia. Calorie and alcohol restriction are often prescribed for hypertriglyceridemic subjects. When these subjects lose weight their serum triglycerides often decrease, secondary to a diminution in hepatic triglyceride secretion. There is also a reduction in insulin resistance leading to an improvement in carbohydrate tolerance. Because some hypertriglyceridemic subjects over-synthesize triglycerides after alcohol ingestion, alcohol restriction is important in the dietary therapy of these patients. Although controversial, the restriction of cholesterol and saturated fat intake is often prescribed for hypercholesterolemic subjects. Recent evidence show (a) As the daily absolute cholesterol intake increases, the % absorbed is decreased but the amount absorbed per kg body weight is increased. (b) Hypercholesterolemic subjects differ from normal subjects in their response to cholesterol and fat intake. (c) A high cholesterol and high saturated fat diet increases the cholesterol concentration in all lipoprotein fractions. A low cholesterol and high polyunsaturated fat diet has the opposite effect. (d) These diets also affect serum apoprotein levels (apo B and apo A-I). It is becoming evident that hyperlipidemic subjects respond differently from normal subjects to dietary changes. For these subjects, at greater risk of developing atherosclerosis, dietary therapy is important.

Alcohol Drinking↗

Differential localization of human pancreas cancer-associated antigen and carcinoembryonic antigen in homologous pancreatic tumoral xenograft.

Tissue localization of a human pancreas cancer-associated antigen (PCAA) and carcinoembryonic antigen (CEA) was studied in a homologous pancreatic tumoral xenograft, a human pancreatic cancer line established from ascites (AsPC-1), with the use of the indirect immunofluorescence technique with specific anti-PCAA and anti-CEA antisera. Histologically, AsPC-1 xenograft was composed of mucinous adenocarcinoma of variable size and degree of glandular differentiation. PCAA was selectively associated with the columnar cytoplasm, was involved primarily in the epithelial proliferation, and originated at the basal aspect of the glands. In contrast, CEA appeared diffuse and was found predominantly in the cuboidal cells, with higher intensity at the luminal border and in mucin. Furthermore, growth comparison of the AsPC-1 adenocarcinoma revealed that, except in the juvenile gland that was morphologically consistent with grade 1 (G1) carcinoma in situ, the number of PCAA-positively stained cells decreased from G1 to grade 4 epithelial differentiation. In well-differentiated adenocarcinoma and degenerating adenocarcinoma, cells positive for PCAA were released into the lumen of the glands, whereas in poorly differentiated adenocarcinoma these cells were often scattered singly and/or in focal clusters and disappeared in very poorly differentiated adenocarcinoma. This study showed that the PCAA was different from CEA in its immunologic reactivity and distribution in its homologous tumoral tissues, in which PCAA was predominantly associated with the proliferative phase of the malignant epithelium. These results also indicated the potential applicability of this antigenic expression in the etiology, disease grading, and staging of human pancreatic cancer.

Adenocarcinoma↗

Serum high density lipoprotein cholesterol in patients with abnormal coronary arteries.

Previous studies showing the inverse relationship between high density lipoprotein cholesterol (HDL-C) and coronary artery disease were based on myocardial infarction survivors and presumably normal subjects. To determine whether a similar relationship exists between patients with abnormal coronary arteries (ACA) and those with normal coronary arteries (NCA), the serum HDL-C and other lipoproteins of these patients and those of a group of presumably healthy control subjects (CTL) were determined. The ACA males had lower HDL-C and % HDL-C but higher TG, VLDL-TG, LDL-C/HDL-C and VLDL-C/HDL-C than the NCA and CTL males. They also had higher VLDL-C and % VLDL-C than the CTL males. Adjustment of HDL-C for serum TG eliminated the difference in HDL-C between the ACA and NCA groups but that between ACA and CTL groups remained. The ACA females had lower % HDL-C than the NCA and CTL females. They also had lower HDL-C but higher LDL-C/HDL-C and VLDL-C/HDL-C than the CTL females. The NCA and CTL groups did not differ in any of the lipid variables, although the NCA group values were intermediate to those of the ACA and CTL groups. Using various lipoprotein profiles, it was possible to classify the patients into the 3 groups.

Adult↗

Pancreatic alpha and beta cell function in familial dysbetalipoproteinemia.

Resistance to both insulin and glucagon have been considered as possible causes of primary hypertriglyceridemia. In the present research, we have compared insulin and glucagon secretion in five hyperlipidemic patients with familial dysbetalipoproteinemia with five normolipidemic control subjects matched for age, sex and adiposioty. Plasma insulin and glucagon concentrations mesaured during standard oral glucose tolerance and arginine infusion tests were similar in the two groups. Blood glucose fell transiently in the controls, but not in the patients, during the Himsworth test (100 g glucose orally plus 0.05 U insulin per kg body weight intravenously). There were no significant differences in plasma FFA concentrations and responses during all tests between the groups. The percentage reduction in plasma triglyceride concentration during infusion of arginine was similar in the two groups. These results suggest that the patients with familial dysbetalipoproteinemia were slightly less insulin sensitive than the controls. However, primary insensitivity to glucagon or insulin does not appear to be fundamental to the pathogenesis of hyperlipidemia in familial dysbetalipoproteinemia.

Adult↗

The effect of a high cholesterol and saturated fat diet on serum high-density lipoprotein-cholesterol, apoprotein A-I, and apoprotein E levels in normolipidemic humans.

The effects of a high cholesterol, high saturated fat diet on serum high density lipoprotein cholesterol, apo A-I, and apo E levels were studied in six normolipidemic subjects. The study was done on an outpatient basis and mixed natural foods normally consumed by humans were used. When compared with a low cholesterol (98 mg/day) high polyunsaturated fat (P/S ratio 1.6) diet, the high cholesterol (1021 mg/day), high saturated fat (P/S ratio 0.4) diet increased serum cholesterol (23%) by raising the cholesterol concentration in very low-density lipoproteins (59%), low-density lipoproteins (15%), and high-density lipoproteins (30%). The low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol ratio fell significantly from 1.78 to 1.58. The increased high-density lipoprotein-cholesterol was associated with an elevation of serum apo A-I but not apo E. Serum triglycerides did not change significantly.

Adult↗

HDL-cholesterol: the negative risk factor for coronary heart disease.

High density lipoprotein cholesterol (HDL-cholesterol) has emerged as a negative risk factor for coronary heart disease. Humans with low levels of HDL-cholesterol are at greater risk of developing coronary heart disease whereas those with high levels are less prone. The epidemiological and biological evidence of this association are strong. As a predictor of coronary heart disease risk, HDL-cholesterol is independent of the other risk factors and is the most powerful lipid predictor. Both genetic and environmental factors influence the serum HDL-cholesterol level. Two physiological mechanisms may explain the presumed protective effect of HDL-cholesterol. However, controlled trials of intervention on the effect of rising HDL-cholesterol on coronary heart disease risk are not yet available. The physician is recommended to include HDL-cholesterol determination as part of his approach to the management of hyperlipoproteinemia. But he is cautioned against the pitfalls of methodology and data interpretation.

Adult↗