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Biomedical subjects

R H Rao

Publications and source records attributed to R H Rao.

At least 37 records · Page 2Linked to original sources
PubMed1991

Chronic undernutrition accentuates insulin deficiency in rats with mild streptozocin-induced diabetes.

The effect of chronic undernutrition on coexisting diabetes mellitus was studied in pair-fed littermate rats with mild streptozocin-induced diabetes. They were either fed ad libitum or 50% food restricted for 9 wk. Undernourished diabetic rats, in which weight gain was reduced by 40%, had significantly higher glucose intolerance (mean +/- SE, fractional rate of glucose disappearance during glucose tolerance test [Kgtt] 1.77 +/- 0.16) than diabetic littermates fed ad libitum (2.33 +/- 0.21, P less than 0.05) or nondiabetic controls (3.8 +/- 0.7, P less than 0.01). The total area under the insulin response curve was significantly reduced in both groups of diabetic rats, but the undernourished group showed a 45% greater reduction in overall secretion than normally nourished diabetic littermates (21.3 +/- 2.7 vs. 39.4 +/- 6.3 nM.min in the diabetic group, P less than 0.01, and 65.7 +/- 6.1 nM.min in controls). There was also a marked reduction in first-phase insulin secretion in the undernourished rats (4.75 +/- 0.24 vs. 9.84 +/- 1.36 nM, P less than 0.05, and 14.3 +/- 1.8 nM, P less than 0.01, respectively, in normally nourished diabetic littermates and controls). After refeeding, a significant improvement occurred in Kgtt (to 2.67 +/- 0.24, P less than 0.01) and first-phase insulin secretion (to 9.69 +/- 1.65 nM, P less than 0.05). The postrefeeding values were not different from those in the normally nourished diabetic littermates, indicating that the effect was fully reversible and solely attributable to undernutrition rather than to enhanced beta-cell cytotoxicity from streptozocin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Purification and partial characterization of intestinal acid lipase.

Intestinal acid lipase is an enzyme whose greatest specific activity is localized to the villus tips of the proximal intestine (Rao, R.H. and Mansbach, C.M. (1990) Biochim. Biophys. Acta 1043, 273-280). This suggests that it plays a role in the processing of dietary lipids. We purified the enzyme in order to better characterize it. Acid lipase was isolated from intestinal mucosa of rats by a combination of ammonium sulfate precipitation, butanol extraction and chromatography on DEAE Bio-Gel, CM Bio-Gel and Sephadex G-75. This resulted in a single protein of Mr 53,700 on SDS-polyacrylamide gel electrophoresis. The isolation scheme produced a 3344-fold purification resulting in an enzyme whose specific activity was 801 mumols/min per mg protein. The yield was 50%. The purified enzyme was stimulated (20-fold) by the addition of tauro- or glycocholate but no other conjugated bile acid. A sharp peak in activity occurred at pH 5.6. The pI of the enzyme was 6.2. The reaction products produced under prolonged incubation suggested that monoacylglycerol was not hydrolyzed since an overabundance of monoacylglycerol was found with respect to the amount of fatty acid produced. These results suggested that intestinal acid lipase is potentially important in the metabolism of dietary lipids. Its proportionate role awaits further documentation.

Animals↗
PubMed1990

Acid lipase in rat intestinal mucosa: physiological parameters.

Previous studies have shown that up to a half of infused triacylglycerol does not exit the intestine via lymphatics. This suggests the presence of a mucosal lipase which could provide fatty acids for potential transport via the portal vein. The present study describes an acid-active lipase in rat intestinal mucosa. Acid lipase was assayed using a glyceryl tri[14C]oleate emulsion (pH 5.8). Mucosal homogenates were differentially centrifuged to yield cellular organelles and cytosol. Cells were sequentially released from villi using citrate and EDTA. The enzyme was found to be most active in the proximal quarter intestine and in the upper third of villi. Its greatest activity was in the lysosomal fraction. Esophageal diversion demonstrated that lingual lipase was not the precursor of the mucosal acid lipase. Bile salts stimulated activity 3- to 5-fold, but other neutral or anionic detergents were inhibitory. Of the detergents tested, taurocholate at super critical micellar concentrations could restore activity only with SDS. Sepharose 6B chromatography suggested that the enzyme partitioned into an SDS and taurocholate mixed micelle. We conclude that mucosal acid lipase is a distinct, intrinsic enzyme of the intestinal mucosa. It is predominantly lysosomal in origin. The location of its greatest activity in the villus tips of the proximal intestine suggests that it is potentially involved in mucosal triacylglycerol disposal.

Acid Phosphatase↗
PubMed1990

Chronic undernutrition may accentuate the beta cell dysfunction of type 2 diabetes.

Seven undernourished and seven obese, insulin-requiring type 2 diabetic subjects, who were matched for age, sex, and duration of diabetes, were subjected to oral glucose tolerance tests. Although fasting glucose and free insulin levels were similar in both groups, glucose tolerance was markedly worse in the undernourished subjects, with a mean incremental glucose area (+/- SE) of 22.8 +/- 2.3 mmol/l.h vs. 12.4 +/- 1.3 in the obese diabetic subjects (P less than 0.001). The incremental insulin response (area under the curve) to oral glucose in the undernourished group (39.3 +/- 7.9 mU/l.h) was 50% lower than the response in both the obese group (89.2 +/- 19.9, P less than 0.001) and a group of non-diabetic, normal weight-for-height subjects (77.1 +/- 5.7, P less than 0.01). Peak insulin levels were similarly reduced to approximately half the levels seen in the obese and control groups (P less than 0.01). Undernutrition is known to impair both glucose tolerance and insulin secretory reserve by reducing the beta cell number, size, and granulation. It is concluded that chronic undernutrition accentuates beta cell dysfunction in undernourished diabetics, leading to increased glucose intolerance.

Blood Glucose↗
PubMed1989

Bilateral massive adrenal hemorrhage: early recognition and treatment.

PURPOSE: To develop a clinical perspective on bilateral massive adrenal hemorrhage and an algorithm for its diagnosis and treatment. DATA IDENTIFICATION: Case reports were identified through a computer search using MEDLIN (1976 to 1987), and from bibliographies in review articles (up to 1978). STUDY SELECTION: Twelve reports published since 1978 were found. DATA EXTRACTION: Data from 20 recently reported cases and 5 cases from personal records were compared with data from 142 previously reported, autopsy-proven cases summarized in a 1978 review article. RESULTS OF DATA ANALYSIS: Thromboembolic disease, coagulopathy, and the postoperative state were the three major risk factors. Except for abdominal pain and remittent fever, clinical features were not helpful in diagnosis. A fall in hemoglobin, and progressive biochemical hypoadrenalism were important clues. Diagnosis was confirmed by computed tomography and an absent cortisol response to intravenous corticotropin. Long-term follow-up showed complete atrophy and functional failure of the adrenal gland. CONCLUSIONS: Death from bilateral massive adrenal hemorrhage can be prevented by pre-emptive steroid therapy in high-risk patients who have certain clinical and laboratory features.

Adolescent↗
PubMed1987

Thyrotropin hyperresponsiveness to TRH despite hyperthyroxinemia in amiodarone-treated subjects.

Pituitary responsiveness to TRH was assessed prospectively over 24 weeks, in 15 patients receiving 300 mg amiodarone a day. All developed significant hyperthyroxinemia (both total and free), and marked elevations in reverse T3 compared to pretreatment levels. Although basal TSH levels were unchanged in all of them, TSH increased by greater than 50% when compared to pretreatment responses, in eight patients, while they remained unchanged (+/- 15%) in the remaining seven. All eight with exaggerated responses also showed significant reductions (P less than .001) in plasma levels of total and free T3, whereas in the seven who did not show any increase in TSH responses, T3 levels were unchanged. The increase in TSH response to TRH was strongly correlated (r = -.82, P less than .001) with T3 levels. Total and free T4 levels were equally elevated in both groups. These observations indicate that amiodarone effectively blocks the suppressive effect of hyperthyroxinemia on TSH secretion, and that T3 is the mediator of thyroid feedback control in amiodarone treated patients.

Amiodarone↗
PubMed1987

Intramuscular glucagon as a provocative stimulus for the assessment of pituitary function: growth hormone and cortisol responses.

The response of plasma growth hormone and cortisol to the intramuscular injection of 1 mg glucagon was used to assess anterior pituitary function in a group of 97 normal subjects (23 men, 74 women). Ninety-three subjects (96%) responded with a peak GH of at least 8 ng/mL, and 89 (92%) had either a peak cortisol of at least 500 nmol/L (18 micrograms/dL) or a maximal increment in plasma cortisol of at least 250 nmol/L (9 micrograms/dL) above the baseline. In 12 subjects, a second test showed that the responses were reproducible. A greater proportion of subjects over the age of 50 failed to achieve a peak GH of 10 ng/mL (7 of 20, 35%) compared to those who were either under 30 (1 of 37, 2.7%) or between 30 and 50 (4 of 40, 10%) (chi 2 = 12.85, P less than .005). GH responses were not affected by sex or elevation of the basal level of GH. In contrast, cortisol responses were smaller in men and in individuals with high basal cortisol levels but were not affected by age. Mild nausea in approximately 30% of subjects (29 of 97), and transient vomiting and retching in approximately 10% (10 of 97) were the only side effects that were noted. Glucagon is therefore a safe and reliable alternative to insulin-induced hypoglycemia for the assessment of both somatotrophic and corticotrophic function.

Adolescent↗
PubMed1987

Inhibitor of calmodulin and cAMP phosphodiesterase activity in BB rats.

Diabetes mellitus in humans is associated with increased plasma and tissue levels of cAMP and decreased cAMP phosphodiesterase (PDE) activity. Calmodulin (CM) is a low-molecular-weight protein essential for activation of cAMP PDE. The inhibitor (INH) is a low-molecular-weight substance that inhibits the activity of CM in multiple systems, including PDE. Spontaneously diabetic BB rats (SDR) and their nondiabetic littermates (NDR) were used in this study. Holtzman rats were rendered diabetic by streptozocin (STZ). STZ-induced diabetic rats (STZ-DR) and BB rats were studied with and without the benefit of insulin therapy. Calmodulin was assayed both by bioassay and by specific radioimmunoassay. The inhibitor was bioassayed by its ability to inhibit CM-activated PDE. Results showed that both spontaneous and STZ-induced diabetes are associated with a decrease in activity of the low-Michaelis constant (Km) cAMP PDE in the liver (39%, SDR; 70% STZ-DR). Calmodulin activity was also decreased in the livers of both animals (13%, SDR; 68%, STZ-DR). Similar data were obtained for NDRs. The inhibitor, on the other hand, was increased in the livers of untreated SDRs and STZ-DRs (155%, SDR; 125%, STZ-DR). No change was noted for NDRs. All these changes were restored toward normal after treatment with insulin. These data suggest that in diabetes the defect in the cAMP PDE-CM-INH system is demonstrated in both an environmental model, as illustrated by STZ-DRs, and a genetic model, as shown by SDRs and NDRs. The inhibitor activity, however, is not changed significantly in NDRs. We speculate that the inhibitor activity plays a role in dictating whether the genetic NDR will or will not become clinically diabetic.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Strict nocturnal diabetic control diminishes subsequent glycemic escape during acute insulin withdrawal.

Five Type 1 (insulin dependent) diabetic patients with no endogenous insulin secretion and very low antiinsulin antibody levels (IBC less than 4%) were studied twice. Nocturnal plasma glucose was maintained by intravenous insulin just beyond each extreme of the normal range, either "hypoglycemic," at 2.71 +/- 0.03 mmol/L, or "hyperglycemic," 8.59 +/- 0.13 mmol/L. Glucose turnover measurements were performed before and after insulin was discontinued the following morning. The steady state plasma glucose concentration achieved during subsequent glycemic escape was significantly lower following nocturnal hypoglycemia, (16.1 +/- 0.3 v 20.2 +/- 0.03 mmol/L; P less than 0.01). The initial rate of rise of plasma glucose was identical in both groups. Free insulin levels, although significantly higher in the hypoglycemic study, before withdrawal, 24.3 +/- 6.0 v 13.3 +/- 0.8 mU/L, (P less than 0.01), fell to similarly low levels 1 hour after insulin withdrawal. Free fatty acid and total ketone concentrations were normalized during hypoglycemia, but remained elevated in the hyperglycemic group. Lactate concentrations were not different in the two studies. During glycemic escape glucose appearance rate (Ra) rose faster following hypoglycemia, but similar final rates were achieved in each group. When related to plasma glucose concentration glucose uptake (Rd) was normal following hypoglycemia and remained persistently greater than the hyperglycemic group throughout the 5 hours following insulin withdrawal. Plasma cortisol, pancreatic glucagon, and growth hormone levels were not significantly different in the two groups following withdrawal. It is suggested that the persistent normal glucose uptake, following glycemic control that has been sufficient to normalize plasma metabolites, will limit glycemic excursions caused by acute reductions in plasma-free insulin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Iodine kinetic studies during amiodarone treatment.

Iodine kinetic studies were performed serially in 15 patients taking 300 mg amiodarone/day for 6 months to assess the biological significance of the high iodine content of the drug. Urinary inorganic iodide excretion increased from 0.25 +/- 0.03 (+/- SE) mumol/mmol creatinine before treatment to over 7 mumol/mmol during therapy. Thyroid iodide clearance fell from 5.93 +/- 0.82 ml/min to less than 0.5 ml/min, while plasma inorganic iodide rose from 0.05 +/- 0.01 mumol/liter to approximately 2.2 mumol/liter during treatment. Thyroid absolute iodide uptake rose from 16.3 +/- 2.7 to 54.6 +/- 5.7 nmol/h after 6 weeks of therapy (P less than 0.001). Thereafter, it progressively declined, but it was still significantly elevated (32.0 +/- 4.3 nmol/h) after 24 weeks (P less than 0.01). The calculated daily excretion of inorganic iodide rose to over 80 mumol during the study, accounting for about 10% of amiodarone iodine. During this time, the patients all had the characteristic plasma thyroid hormone changes associated with amiodarone therapy, i.e. increased T4, free T4, and rT3 and decreased T3, while remaining clinically euthyroid. The massive increase in available inorganic iodide during amiodarone treatment is probably responsible for the induction of both the hypothyroidism and the thyrotoxicosis that can occur in patients receiving the drug.

Adult↗
PubMed1985

Effects of phthalic acid esters on drug metabolizing enzymes of rat liver.

Di(2-ethylhexyl)phthalate (DEHP) inhibited UDP-glucuronyltransferase activity of rat liver in vitro and in vivo. Diethyl phthalate and dimethoxyethyl phthalate also inhibited this enzyme in vitro. On the other hand, DEHP did not inhibit the activity of the cytosolic enzyme N-acetyltransferase; it also did not alter the levels of rat liver microsomal cytochrome P-450 in vitro. It is suggested that DEHP may alter the composition of microsomal phospholipids.

Acetyltransferases↗
PubMed1985

Developmental changes in the conversion rates of di(2-ethylhexyl) phthalate to monoethylhexyl phthalate in rats.

The activities of liver, lung, and kidney of rats of various age groups and that of placenta in hydrolyzing di(2-ethylhexyl) phthalate to mono(2-ethylhexyl) phthalate have been measured. Male and female rats of 45 d of age, neonatal rats within 12 h of parturition, and fetuses and placenta on d 19 of gestation were used. The liver was most active in all age groups; however, the lung and the kidney also had considerable activity. The tissues of the fetuses and the neonate had significant activity. The Km values of the enzyme were 4 mM in the neonatal liver and 5.9 mM in the adult liver.

Animals↗
PubMed1984

Properties and characterization of low molecular weight inhibitor of calmodulin-dependent cAMP phosphodiesterase from rat liver.

We have identified two different species of inhibitors of calmodulin-dependent cAMP phosphodiesterase: 1) a low molecular weight (LMW) and 2) a high molecular weight (HMW) form. These inhibitors are extracted from rat liver. Both LMW and HMW inhibitors are heat-stable, acidic in nature and lose activity with prolonged storage and/or repeated freezing and thawing. The low molecular weight inhibitor has been purified to about 7,000-fold with 300% recovery. LMW inhibits calmodulin-dependent cAMP phosphodiesterase regardless of the source of calmodulin (e.g. fat, brain, heart, erythrocytes). LMW appears to be lipid in nature with a molecular weight of 1,500-5,000. The role of these inhibitors in diabetes and mechanism of action of insulin is presented.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Glucose tolerance in subclinical pyridoxine deficiency in man.

Oral glucose tolerance tests were carried out in 16 clinically normal subjects with pyridoxine deficiency (as adjusted by red cell transaminase activity and the 6h tryptophan load test), and in 16 nondeficient controls. The deficient subjects had fasting normoglycemia with hypoinsulinemia (p less than 0.01), and a normal postglucose increment in insulin, but peak blood glucose and incremental glucose area were both significantly lower than in the controls (p less than 0.01). Suppression of growth hormone during the glucose tolerance test was similar in both groups. These data are interpreted as indicating an enhanced sensitivity to the hypoglycemic action of insulin in pyridoxine-deficient individuals. Supplementation with pyridoxine in these subjects resulted in a tendency for insulin levels to rise (NS), and a significant increase in growth hormone levels. Impairment of growth hormone reserve may be the basis for the increased insulin sensitivity. Subclinical pyridoxine deficiency of the degree seen in this study is apparently associated with improved, rather than impaired, glucose tolerance.

Adult↗
PubMed1983

Suppressible glucagon secretion in young, ketosis-resistant, type "J" diabetic patients in India.

Plasma glucagon levels were measured in young individuals with severe, insulin-dependent, juvenile-onset diabetes mellitus to study whether differences in glucagon secretion were related to ketosis proneness and resistance. Fasting glucagon levels were similarly elevated in both classical, ketosis-prone, type I diabetic subjects and ketosis-resistant, type "J" subjects [70 +/- 7 pmol/L (mean +/- SEM) and 81 +/- 10 pmol/L, respectively] compared with nonobese, nondiabetic controls (36 +/- 3 pmol/L, P less than 0.01). After oral glucose administration, however, glucagon responses were strikingly dissimilar in the two groups. In type I diabetic individuals, glucagon rose paradoxically during OGTT, by 21 +/- 4 pmol/L, an increase of 33 +/- 10%; on the other hand, glucagon levels in type "J" diabetic individuals fell by 28 +/- 7 pmol/L, a decrease of 33 +/- 5%. There was no measurable increase in plasma free insulin during OGTT in either group. Postprandial glucagon suppressibility may be relevant to the ketosis resistance that is characteristic of type "J" diabetes.

Adolescent↗
PubMed1981

Deacylation of dipalmitoyllecithin by phospholipases A in alveolar macrophages.

Optimal conditions in vitro were established for the assay of phospholipases A of Bacillus Calmette Guerin-induced alveolar macrophages that deacylated dipalmitoyllecithin in the alkaline pH range. Sodium deoxycholate and Ca++ were found to stimulate both phospholipases A1 and A2, whereas sodium dodecylsulfate strongly inhibited both enzyme activities. Other detergents like Triton X-100, Triton WR-1339, and Tween-20 activated phospholipase A1, whereas they had no effect on or slightly inhibited the phospholipase A2 enzyme. These phospholipases preferentially removed palmitic acid regardless of the position of palmitic acid on the phospholipid molecule and were more active on phosphatidylcholines than phosphatidylethanolamines. This suggests a role for macrophage phospholipases A in the clearance of saturated lecithins in the pulmonary surfactant complex.

Animals↗