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Biomedical subjects

M T Subbiah

Publications and source records attributed to M T Subbiah.

At least 73 records · Page 4Linked to original sources
PubMed1984

Abnormal bile acid pool and composition in neonates of spontaneously diabetic Wistar BB rats and its change during development.

Streptozotocin-induced diabetes during pregnancy in rats causes a decrease in primary bile acid pool in neonates. To rule out direct drug effect on the fetus as the basis for this change, studies of bile acid pool and composition at birth and during subsequent development was carried out in neonates of spontaneously diabetic Wistar BB rats and compared to control neonates. The cholic acid pool in neonates of diabetic rats was lower when compared to control neonates at birth. The pool of secondary bile acids was markedly increased in neonates of diabetic rats, with increases in lithocholic and 3 beta,12 alpha-dihydroxycholanoic acid. With age, the cholic acid pool of neonates from diabetic rats was increased and at 3 months of age it was actually higher than in control neonates. The pool of chenodeoxycholic at diabetes onset age was lower in neonates of diabetic rats. HDL-cholesterol was lower in neonates of diabetic rats at 1 week, but this reversed at 3 months of age. These studies firmly establish that neonates of diabetic rats have abnormal bile acid pool and composition at birth which changes to adult diabetic pattern with age.

Age Factors↗
PubMed1984

Evidence for the presence of non-lipoprotein factors in diabetic serum capable of stimulating rat hepatic cholesterol-7 alpha-hydroxylase in vitro.

Experimental diabetes in the rat has been shown to result in marked increases in bile acid pool and synthesis. In this study, mechanisms responsible for the increased bile acid synthesis was examined in rats made diabetic with streptozotocin. Our results indicate that a) in diabetic rats, hepatic cholesterol-7 alpha-hydroxylase activity is increased by 100%, b) this increased activity is not due to a higher stimulating activity of cell supernatant factors, but c) may be due to a non-lipoprotein factor(s) in diabetic serum capable of stimulating (by 100%) cholesterol-7 alpha-hydroxylase activity in control livers to the level noted in diabetic animals.

Animals↗
PubMed1984

Effect of streptozotocin-induced diabetes in neonatal rat on bile acid pool changes in adult life: selective sensitivity in females.

The effect of streptozotocin-induced diabetes in neonatal rat on the bile acid pool and composition during adult life was investigated. Unlike the effect of diabetes in adult rats (where bile acid pool increases markedly), neonatal diabetes caused a reduction in bile acid pool in adult life in females (but not in males) with significant reduction in both cholic and chenodeoxycholic acids. Upon challenge with dietary cholesterol, only the female diabetic rat responded with a further reduction in total bile acid pool. These studies demonstrate a selective sensitivity in the female diabetic rat with regard to diabetes-induced changes in bile acid pool.

Aging↗
PubMed1984

Streptozotocin-induced diabetes in the neonatal rat: effect on plasma lipids and aortic prostaglandin synthesis in adult life.

The effect of streptozotocin (STZ)-induced diabetes in neonatal male rats on plasma lipids and aortic 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) synthesis in adult life was investigated. A reduction (62% of control) in aortic 6-keto-PGF1 alpha was observed only after maturity, at 17, but not 8, weeks of age. In contrast to STZ-induced diabetes in adult rats, who experience marked elevations in both plasma triglyceride (TG) levels (up to 13-fold) and total cholesterol (CH) levels (2-fold), plasma TG levels were never elevated and plasma total CH levels were significantly elevated (37%) only at 17 weeks of age. Thus, the reduction in aortic 6-keto-PGF1 alpha synthesis was dissociated from alterations in plasma TG levels in adult male rats with diabetes of neonatal origin. A significant elevation (0.31 to 0.48) in the proportion of linoleate (a competitive inhibitor of prostacyclin synthesis) to arachidonate in aortic phospholipids was also found. The results suggest that the reduced aortic synthesis of 6-keto-PGF1 alpha occurring in diabetic rats was not related to hypertriglyceridemia, but may have been related to hypercholesterolemia or altered ratios of linoleate to arachidonate in aortic phospholipids.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Effect of chenodeoxycholic acid feeding during gestation in the rat on bile acid metabolism and liver morphology.

Chenodeoxycholic acid (CDCA) was fed to pregnant rats at the 0.25% level in the diet from Day 11 of gestation to delivery in order to evaluate the effects on (1) maternal tissue bile acid composition, (2) neonatal tissue bile acid composition and cholesterol-7 alpha-hydroxylase activity, and (3) maternal, neonatal, and postnatal liver morphology. Feeding CDCA increased maternal lithocholic acid while significantly decreasing deoxycholic acid, cholic acid, and total bile acids. Feeding CDCA resulted in a significantly higher chenodeoxycholic acid pool in the neonates while neonatal plasma cholesterol and the 7 alpha-hydroxylation of cholesterol was not significantly affected. Morphological examination of maternal, neonatal, and postnatal rat liver revealed no significant hepatotoxicity. This investigation has shown that (a) neonates of CDCA fed dams have a significantly greater pool of CDCA, suggesting maternal-to-fetal transfer of dihydroxy bile acids, (b) neonatal cholesterol-7 alpha-hydroxylase activity and total tissue bile acid pools are not significantly altered by increased pool of CDCA, and (c) no hepatotoxic effects on maternal, neonatal, and postnatal livers were evident with gestational feeding of CDCA at the 0.25% level in the rat.

Animals↗
PubMed1984

Altered aortic prostaglandin synthesis in a mild form of diabetes and the influence of dietary cholesterol.

Extreme hyperglycemia (350 mg/dl) in rats results from streptozocin injection (50 mg/kg) and leads to a reduced aortic capacity for prostacyclin synthesis. Other complications such as hyperlipemia and alterations in body weight gain (loss or no gain) that might be responsible for the altered aortic prostacyclin synthesis occur concurrently. We injected neonatal rats (2 days of age) with intraperitoneal streptozocin to induce chronic mild diabetes (mean plasma glucose, 241 mg/dl) characterized in adult rats by normal body weight gain, normolipemia, and a physical appearance virtually indistinguishable from controls. Plasma insulin levels were reduced in rats with mild diabetes rats to 66% of control levels. A group of control and diabetic rats were given a 0.5% cholesterol diet for 7 weeks to induce hyperlipemia. Rats with diabetes and control rats given the cholesterol diet had elevated plasma insulin levels of 32% and 51%, respectively, and no alteration in plasma glucose levels (compared with respective controls), suggesting a state of insulin resistance. Aortic synthesis of 6-keto-PGF1 alpha from endogenous arachidonic acid was reduced in rats with mild diabetes and normolipemia or hyperlipemia. In contrast, the aortic conversion of exogenous arachidonic acid to 6-keto-PGF1 alpha was reduced only in rats with mild diabetes and hyperlipemia. Our results demonstrate that: (1) aortic prostacyclin synthesis is reduced in mild diabetes in the absence of alteration in plasma lipid levels and body weight gain; (2) aortic prostacyclin synthesis from endogenous arachidonic acid is more sensitive to diabetes than synthesis from exogenous arachidonic acid; (3) dietary cholesterol induces a state similar to insulin resistance and interacts with mild diabetes, resulting in reduced aortic prostacyclin synthesis from exogenous arachidonic acid.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Effect of ethinylestradiol on arachidonic acid incorporation, release, and conversion to prostaglandins in rabbit platelets.

Intramuscular administration to female rabbits of 2 mg/kg ethinylestradiol every other day for 10 days increased the uptake and incorporation of [14C]arachidonic acid into platelet lipids, and increased the proportion of [14C]arachidonic acid released from platelets after stimulation by thrombin. The conversion of [14C]arachidonic acid to thromboxane B2 did not differ between the control and ethinylestradiol-treated groups. Thus, the results of this study indicate that the major site in the prostaglandin metabolic pathway influenced by estrogen is the incorporation and release of arachidonic acid in platelet phospholipids.

Animals↗
PubMed1983

Specific effect of dietary saturated fat on rat aortic 6-keto-PGF1 alpha synthesis.

The effect of dietary lard and corn oil-supplementation on rat aortic 6-keto-PGF1 alpha synthesis from both exogenous and endogenous arachidonic acid was investigated. Only lard-supplementation resulted in any change when compared to rats fed normal chow. Lard-supplementation resulted in both a significant increase in the conversion of exogenous arachidonic acid to 6-keto-PGF1 alpha and a significant decrease in the ratio of linoleate to arachidonate in aortic phospholipids. Basal aortic synthesis of 6-keto-PGF1 alpha from endogenous arachidonic acid was not different for any group. We conclude that at least for the aortic conversion of exogenous arachidonic acid to 6-keto-PGF1 alpha the level of inhibitor linoleic acid in tissue phospholipids may be important.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Chronic suppression of cholesterol 7 alpha-hydroxylase by dietary chenodeoxycholic acid in neonatal guinea pigs: its effect on subsequent bile acid metabolism in the adult.

Treatment of neonatal guinea pigs with cholestyramine persistently increases the activity of hepatic cholesterol 7 alpha-hydroxylase (CH-7 alpha), the rate-limiting enzyme of bile acid biosynthesis. In this study, we examined whether CH-7 alpha activity could be persistently inhibited by manipulations (chenodeoxycholic acid feeding) during neonatal life. Male Hartley guinea pigs (2-3 days old) were fed 0.25% chenodeoxycholic acid (CDCA)-supplemented diet for 10 days or 6 weeks. Feeding CDCA for 10 days increased plasma cholesterol [controls (C), 25 +/- 3 vs. CDCA, 34 +/- 2 mg/dl]. Bile acid pool in animals fed CDCA for 10 days was nearly fivefold greater than controls (C, 5.8 +/- 0.3 vs. CDCA, 29.1 +/- 0.9 mg/100 g body weight), whereas CH-7 alpha activity was almost completely inhibited [C, 1.83 +/- 0.4 vs. CDCA, 0.02 +/- 0.02 pmol/(mg . minute)]. Four weeks after stopping CDCA feeding, CH-7 alpha was greater in the CDCA-fed animals (C, 0.47 +/- 0.03 vs. CDCA, 0.67 +/- 0.05). This was associated with a greater bile acid pool in these animals (C, 3.0 +/- 0.2 vs. CDCA, 5.8 +/- 0.4). We conclude that CDCA fed to neonatal guinea pigs inhibits CH-7 alpha activity. This inhibition is not permanent, however, since CH-7 alpha activity increases following withdrawal from chronic CDCA feeding.

Age Factors↗
PubMed1983

Decreased atherogenic response to dietary cholesterol in pigeons after stimulation of cholesterol catabolism in early life.

Cholesterol catabolism was stimulated in 6-wk-old White Carneau pigeons using a laboratory stock diet containing 1.3% cholestyramine resin. After 8 wk on this diet the animals were returned to control stock diet (no resin) for another 8-wk period. When subsequently challenged with a diet containing 0.5% cholesterol, cholestyramine-pretreated pigeons exhibited significantly lower serum cholesterol level when compared with controls and this "hyporesponder" behavior persisted throughout the study period. Furthermore, the aorta of cholestyramine-treated animals exhibited significantly (a) lower prevalence and severity of atherosclerosis and (b) lower cholesterol content. These studies demonstrate for the first time that enhancement of cholesterol catabolism in early life improves resistance to diet-induced atherosclerosis in later life in this avian model.

Aging↗
PubMed1983

The role of human growth hormone in the regulation of cholesterol and bile acid metabolism.

Cholesterol and bile acid metabolism was studied in 16 children with human GH (hGH) deficiency (11 with isolated hGH deficiency and 5 with multiple trophic hormone deficiency) before and after 6 months of hGH therapy. We measured plasma lipid concentrations, biliary lipid composition, and cholesterol saturation indices; calculated the bile acid pool size measured by the isotopic dilution technique using the stable isotope chenodeoxycholic-[11,12-d2] acid; and measured cholesterol and bile acid synthetic rates by sterol balance techniques. In all 16 patients, plasmas lipid concentrations were unchanged after hGH therapy; total plasma cholesterol was 182 +/- 10 (+/-SEM) mg/dl before and 179 +/- 9 mg/dl after treatment, high density lipoprotein-cholesterol was 47 +/- 2 mg/dl before and 49 +/- 3 mg/dl after treatment, low density lipoprotein-cholesterol was 112 +/- 10 mg/dl before and 111 +/- 8 mg/dl after therapy, and triglyceride was 113 +/- 13 mg/dl before and 107 +/- 10 mg/dl after hGH therapy. Biliary lipid composition and cholesterol saturation in 10 patients were similar to those in controls and unchanged with hGH therapy. Cholesterol synthesis (n = 14) was unchanged (7.6 +/- 1.4 vs. 9.6 +/- 1.2 mg/kg X day); however, bile acid synthesis (n = 15) increased from 3.1 +/- 0.4 to 4.3 +/- 0.6 mg/kg X day (P less than 0.025) after therapy. The chenodeoxycholate pool size (n = 8) was significantly reduced (P less than 0.025) before hGH treatment (416 +/- 64 mg/m2) compared to that in controls (617 +/- 45 mg/m2) and increased to 620 +/- 72 mg/m2 after hGH therapy (P less than 0.05). Chenodeoxycholate pool size expansion during hGH therapy was, at least in part, caused by an increase in hepatic bile acid synthesis. These findings suggest that hGH may indirectly modulate cholesterol metabolism through regulation of hepatic cholesterol 7 alpha-hydroxylase activity, the rate-limiting enzyme of bile acid synthesis.

Adolescent↗
PubMed1982

Prostaglandin synthesis in aorta and platelets of fawn-hooded rats with platelet storage pool disease and its response to cholesterol feeding.

Fawn-hooded (FH) rats possess a hereditary bleeding diathesis and platelet function defect, which is presumably the result of a storage pool deficiency. In this study, we have investigated the prostaglandin synthesis capacity of platelets and aorta from FH rats as compared to Sprague Dawley (SD) rats, after 2 months on a normal or 1% cholesterol diet. No difference was found in thromboxane B2 (TXB2) production by platelets of FH as compared to SD rats. Cholesterol-feeding resulted in an increased TXB2 production by SD platelets, but not FH platelets. FH rat aorta was found to convert significantly less arachidonic acid (AA) to 6-keto-prostaglandin-F1 alpha (PGF1 alpha) and cholesterol-feeding stimulated this reduced capacity. In contrast, cholesterol-feeding in the SD rat reduced aortic 6-keto-PGF1a production. Aggregation of platelet-rich plasma by AA was enhanced in the cholesterol-fed FH rat. This result suggests the possibility of an influence of platelet aggregability on aortic prostacyclin production.

Alprostadil↗
PubMed1982

Effect of feeding beta-sitosterol alone or in combination with cholestyramine during early life on subsequent response to cholesterol challenge in adult life in guinea-pigs.

The effect of feeding 20 g beta-sitosterol/kg alone or in combination with cholestyramine (20 g/kg) during neonatal life of guinea-pigs on their subsequent response to a dietary cholesterol challenge in adult life was examined. 2. beta-Sitosterol pretreated animals showed higher plasma cholesterol values following 2 weeks on a cholesterol challenge (2-5 g/kg) diet, but did not differ significantly from control values for the remainder of the cholesterol challenge period. 3. Guinea-pigs pretreated with beta-sitosterol plus cholestyramine, on the other hand, showed a marked increase in plasma cholesterol levels over those of controls during the cholesterol challenge period, and this "hyper-responder" behaviour was maintained throughout the study period. 4. Despite the increase in plasma cholesterol, beta-sitosterol plus cholestyramine pretreated animals excreted significantly (P less than 0.05) greater amounts of bile acids and total sterols. 5. These findings demonstrate that neonatal pretreatment with beta-sitosterol plus cholestyramine has detrimental effects on the handling of a cholesterol challenge in adult life, and does not achieve the beneficial effect previously noted with pretreatment with cholestyramine alone.

Animals↗
PubMed1982

Effect of enhancement of cholesterol catabolism in guinea pigs after weaning on subsequent response to dietary cholesterol.

Cholesterol catabolism was stimulated (by cholestyramine) in post-weaned guinea pigs for a 4-wk period. The animals were then switched to regular Chow diet for another 4 wk. When subsequently challenged with 0.25% cholesterol-containing Chow, plasma cholesterol level was significantly (p less than 0.05) lower in cholestyramine pretreated guinea pigs when compared to control guinea pigs and this "hyporesponder" pattern was maintained throughout the study period. Cholestyramine pretreated animals continued to excrete significantly (p less than 0.05) higher bile acids even at 4 wk after switching to regular Chow diet. This study demonstrates that stimulation of cholesterol catabolism even at postweaning stages can still be as effective in improving subsequent cholesterol handling capacity as noted previously after manipulation at the neonatal stage.

Age Factors↗
PubMed1982

Development of bile acid biogenesis in the rat: effect of neonatal thyroidectomy, adrenalectomy, and streptozotocin-induced diabetes.

Effect of neonatal thyroidectomy, adrenalectomy and streptozotocin-induced diabetes in rats on the bile acid pool size and composition at weaning was examined. Adrenalectomy caused a significant (p less than 0.05) decrease in the total bile acid pool with significant reductions (p less than 0.05) in both cholic and chenodeoxycholic acids. Thyroidectomy on the other hand caused a specific decrease (p less than 0.05) in chenodeoxycholic acid pool. Streptozotocin-induced diabetes caused (a) a decrease (p less than 0.05) in total bile acid pool with a significant (p less than 0.05) reduction in chenodeoxycholic acid, and (b) an increase in plasma cholesterol levels.

Adrenalectomy↗