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Y C Patel

Publications and source records attributed to Y C Patel.

At least 127 records · Page 7Linked to original sources

Somatostatin analogs. Dissociation of brain receptor binding affinities and pituitary actions in the rat.

We have recently demonstrated the presence of specific receptors for somatostatin (SRIF) in rat brain synaptosomal membranes which appear to mediate its action. Using this system as a radioreceptor assay, we have examined the ability of a wide range of SRIF analogs to interact with these receptors. Although structural modifications in the Trp8 moiety of SRIF resulted in significant enhancement of affinity for binding to the brain SRIF receptors, the different relative specificities of des AA1,2,4,5,12,13 D-Trp8 SRIF (oligo D-Trp8 SRIF), D-Trp8 SRIF and D-5-Br-Trp8 SRIF in the pituitary and the central nervous system (CNS) suggest that basic differences exist between SRIF receptors present in the brain and the pituitary.

Animals↗

Immunoreactive adrenocorticotropin in the gastrointestinal tract and pancreatic islets of the rat.

Radioimmunoassayable ACTH is detectable in the gastrointestinal tract and pancreatic islets of the rat by using a midportion ACTH antiserum. Portions of the gastrointestinal tract and isolated pancreatic islets were extracted with 0.1 N HCl. Serial dilutions of the extracts resulted in inhibition curves parallel with human alpha ACTH-(1-39). The highest concentrations were in the isolated pancreatic islets (20 pg/ml protein) and the gastric antrum-pylorus (17.9 +/- 1.2 pg/ml protein). Chromatographic characterization of the stomach extract showed a main peak, with an elution constant identical to that of [125I]iodo-ACTH-(1-39) and an elution pattern identical to that of rat pituitary extracts and medium from incubated rat pituitaries.

Adrenocorticotropic Hormone↗

Antibodies to insulin, pancreatic polypeptide, glucagon, and somatostatin in insulin-treated diabetics.

The hormonal content of the commercial insulins most commonly used in Canada (Connaught) and the USA (Lilly) was measured, and the prevalence of antibodies to these hormones was determined in the serum of diabetics treated with one of these preparations. Connaught insulins contained 62 +/- 10 ng pancreatic polypeptide (PP)/100 U insulin, 11 +/- 2 ng glucagon/100 U, and 56 +/- 16 pg somatostatin (SRIF)/100 U. Lilly single peak insulins contained 693 +/- 41 pg PP/100 U, 8 +/- 2 ng glucagon/100 U, and 323 +/- 174 pg SRIF/100 U, whereas the recently introduced Lilly improved single peak insulins contained 8 +/- 2 ng PP/100 U, 30 +/- 10 ng glucagon/100 U, and 43 +/- 1 pg SRIF/100 U. Lilly highly purified Iletin II pork insulin contained 1.0 ng PP/100 U, 0.4 ng glucagon/100 U, and 19 pg SRIF/100 U. Of 111 diabetics treated with Connaught insulin, 91% had antibodies to insulin, 51% had antibodies to PP, 14% had antibodies to glucagon, and 6% had antibodies to SRIF. Antibodies to PP were also found in 2 control subjects (n = 30). In patients who had taken Connaught insulin for 10 yr or more, 97% had insulin antibodies, 84% had PP antibodies, 14% had glucagon antibodies, and 11% had SRIF antibodies. Fasting serum GH levels were normal in all patients with SRIF antibodies. Cord blood from two pregnancies in insulin-treated diabetic mothers contained antibodies to the same hormones as maternal production of antibodies to insulin, PP, glucagon, and SRIF. The importance of these antibodies in the pathophysiology of diabetes is discussed.

Adult↗

Evidence for somatostatin precursors in human stomach, placenta, and amniotic fluid.

Human stomach, placenta, and amniotic fluid have previously been shown to contain immunoreactive somatostatin (IRS). The present studies were undertaken to further characterize this IRS. Gel chromatography of amniotic fluid revealed only one peak of somatostatin-like immunoreactivity (SLI; mol wt, 15,000) regardless of gestational age. Extracts of human fetal stomach contained three peaks of SLI: 87% of the total IRS coeluted with synthetic tetradecapeptide somatostatin (SRIF), 12% coeluted with synthetic somatostatin-28 (S-28), and 4% coeluted with amniotic fluid SLI. Extracts of 9- to 13-week-old placentas contained 38.9 +/- 5.3 pg IRS/mg protein (range, 21-62 pg IRS/mg protein). Chromatography revealed that 57% of the total IRS coeluted with SRIF, 19% coeluted with S-28, and 23% eluted in a position indicating a molecular weight of 12,000. Serial dilutions of amniotic fluid SLI and material from each peak of stomach and placental SLI showed parallelism with synthetic SRIF. Treatment with 8 M urea and dithiothreitol did not convert any of these SLIs to smaller immunoreactive forms. Incubation of purified amniotic fluid SLI with 1% (wt/wt) L-(tosylamido 2-phenyl)ethyl chloromethyl ketone-trypsin for 90 min resulted in partial conversion to immunoreactive material coeluting with SRIF. When synthetic S-28 was incubated in fresh amniotic fluid at 37 degrees C, it was rapidly degraded (t 1/2 approximately or equal to 25 min). These studies indicate that human amniotic fluid IRS is composed of 15K SLI only, whereas human stomach and placental IRS are heterogeneous, comprising SRIF as well as larger forms of SLI which probably represent SRIF precursors.

Amniotic Fluid↗

Obesity, smoking and atherosclerosis. A study of interassociations.

The data gathered from male autopsied cases (25-64 years of age) in Orleans Parish have been analysed for association between measurements of athetosclerosis and measurements of obesity. The confounding effects of diseases such as hypertension and diabetes have been controlled by excluding from analysis cases known to have such diseases. The confounding effect of age and a measurement of smoking habit on the association between atherosclerosis and obesity has been controlled by the technique of multivariate regression analysis. An inverse association between smoking habit and obesity and the direct associations between smoking habit and atherosclerosis as measured by MCWT (mean coronary wall thickness), CALC (coronary calcification), RLAA (raised lesion in abdominal aorta), and RLCA (raised lesion in coronary arteries) have been confirmed. Positive though weak associations for mesasures of atherosclerosis (MCWT and RLCA) with adipose thickness have been found among whites but not among blacks. Among black cases a weak association between fatty streaks in coronary arteries and adipose thickness was found. It is suggested that obesity itself is not an atherogenic agent but that it is related to one or more atherogenic agents that affect aortas and coronary arteries differentially and that are more intensive among whites than among blacks.

Adipose Tissue↗

Elevated portal and peripheral blood concentration of immunoreactive somatostatin in spontaneously diabetic (BBL) Wistar rats: suppression with insulin.

Immunoreactive somatostatin (IRS) was measured in extracted plasma obtained from the hepatic portal vein (PV) and inferior vena cava (IVC) of acute, untreated, spontaneously diabetic Wistar rats (BBL), insulin-treated diabetic rats, and nondiabetic controls. Acetic acid extracts of the pancreas and entire gastrointestinal tract were assayed for IRS, and the volume density of pancreatic D-, A-, and B-cells was determined by quantitative morphometry. The concentration of IRS in the PV and IVC of the untreated diabetic rats was significantly elevated compared with controls, with a much greater percent increase in the IVC compared with the PV. Insulin treatment for 4-6 wk restored the elevated PV and IVC levels to control values. The pancreatic content of IRS and the volume density of D-cells was severely reduced in the diabetic groups whereas gut IRS was unchanged. These data suggest that the elevated blood levels are secondary to insulin deficiency and result from altered peripheral metabolism and/or increased secretion of IRS most probably from the gut. The increased peripheral blood concentration of IRS raises the possibility of an endocrine role of circulating somatostatin in diabetes. The reduction in pancreatic IRS found in this model is probably secondary to insulitis and contrasts with the D-cell augmentation reported in streptozotocin-diabetic rats.

Animals↗

Measurement, characterization, and source of somatostatin-like immunoreactivity in human amniotic fluid.

Somatostatin-like immunoreactivity (SLI) is widely distributed in tissues and biological fluids. To determine whether SLI is also present in amniotic fluid, samples obtained by amniocentesis from 30 normal and 27 abnormal pregnancies were studied by radioimmunoassay. Direct incubation of [(125)I-Tyr(1)]tetradecapeptide somatostatin (SRIF) with amniotic fluid resulted in 89% tracer degradation. Damage was reduced to <5% when samples were acidified and boiled before the assay. With this technique, SLI was detectable in all normal amniotic fluid samples; the mean level at 15-20 wk of gestation (320+/-55 pg/ml, n = 15) being 4.5 times higher than the mean at 32-43 wk (70+/-12 pg/ml, n = 15) (P < 0.001). In cases of preeclampsia (n = 6), gestational diabetes (n = 5), anencephaly (n = 1), and meningomyelocele (n = 1), SLI values were in the normal range, but in one juvenile diabetic and one patient with chronic renal failure, SLI was undetectable (<10 pg/ml). In a pair of monochorionic diamniotic twins, SLI levels were very different (33 and 197 pg/ml), which suggests that fetal factors are more important than materno-placental ones in determining amniotic fluid SLI. Serial dilutions of amniotic fluid showed parallelism with standard SRIF. When concentrates of pooled amniotic fluid were chromatographed on Sephadex G-25 columns, all SLI eluted in the void volume ahead of SRIF even after treatment with 8 M urea and dithiothreitol. This "big" SLI incubated in amniotic fluid showed 100% stability over 24 h at 37 degrees C, whereas SRIF was rapidly inactivated (t((1/2)) congruent with 7 min). Extracts of placenta and fetal membranes contained no SLI, but small amounts (6-20% of total amniotic fluid SLI) were found in cells from fresh fluid. Radioimmunoassay of SLI in extracts of seven paired cord arterial and venous plasma samples showed no arteriovenous gradient consistent with fetal origin of cord blood SLI. It is concluded that (a) amniotic fluid contains SLI which is of fetal origin and (b) normal levels vary with gestational age. The SLI has a higher molecular weight (>/=5,000) and is more stable in amniotic fluid than SRIF.

Amniotic Fluid↗

Somatostatin secretion from monolayer cultures of neonatal rat pancreas.

Monolayer cultures of neonatal rat pancreas have been characterized as an in vitro system for studying SRIF secretion. Marked 12- and 6-fold potentiation of SRIF release occurred with N-2-O-dibutyryl cAMP monosodium salt and theophylline, respectively. High glucose (300 mg/dl) stimulated SRIF release, whereas galactose was without effect. Exogenous insulin did not alter SRIF release, and the SRIF responses to theophylline and glucose were unaffected by the addition of antiinsulin serum to neutralize the insulin released by these agents. Arginine evoked a significant 2-fold increase in SRIF release. Exogenous glucagon produced slight but not significant stimulation of SRIF release. However, after exposure of the cultures to antiglucagon serum to diminish the concentration of glucagon in contact with the SRIF cells, exogenous glucagon produced a marked enhancement of SRIF secretion. These data suggest that glucose, arginine, glucagon, N-2-O-dibutyryl cAMP monosodium salt, and theophylline stimulate SRIF secretion, probably by direct effects on D cells or through mechanisms other than increased insulin secretion. Monolayer cultures of rat pancreas should provide a powerful in vitro system for studying pancreatic SRIF physiology.

Animals↗

Effect of anterior hypothalamic lesions on neurohypophysial and peripheral tissue concentrations of somatostatin in the rat.

Somatostatin (SRIF) is present in nerve endings in the median eminence (ME) and posterior pituitary. Hypothalamic SRIF containing neuronal perikarya are predominantly located in the anterior hypothalamic area (AHA), a region implicated in the inhibitory control of GH secretion. The effect of AHA lesions on SRIF in the ME, posterior pituitary, pancreas, stomach, and small intestine was studied in the rat in order to elucidate the source of ME and posterior pituitary SRIF and to determine if depletion of hypothalamic SRIF affects peripheral organ concentrations of the peptide. Lesioned animals showed a highly significant (P less than 0.01) 83% and 82% reduction in ME and posterior pituitary SRIF and to determine if depletion of hypothalamic SRIF affects peripheral organ concentrations of the peptide. Lesioned animals showed a highly significant (P less than SRIF concentrations in the pancreas, stomach, and small intestine of the lesioned animals. Plasma and pancreatic insulin and pancreatic glucagon were likewise unchanged. These data suggest that the hypothalamic SRIF pathway begins in the AHA, from where axons of somatostatinergic neurosecretory neurons project to both ME and posterior pituitary. AHA lesions have no effect on gut and pancreatic SRIF or pancreatic insulin and glucagon.

Animals↗

Somatostatin and pancreatic polypeptide secretion: effects of glucagon, insulin, and arginine.

The isolated perfused canine pancreas with duodenal exclusion was used to examine islet hormone output in response to arginine and exogenous glucagon and insulin. Exogenous glucagon (100 ng/ml) stimulated insulin and somatostatin secretion, which occurred in a biphasic pattern. The insulin response to glucagon was markedly enhanced by increased perfusate glucose, unlike the somatostatin response, which was little affected. The insulin and somatostatin responses were seen between 15 and 45 s after the glucagon stimulus. Pancreatic polypeptide secretion was uninfluenced by exogenous glucagon. Biphasic release of glucagon, somatostatin, and pancreatic polypeptide was evoked by 10 mM arginine, the responses first being apparent within less than 30 s. Exogenous insulin (50 mU/ml) infused for 10 min had no statistically significant effect on glucagon, somatostatin, or pancreatic polypeptide secretion. This study suggests that these four islet hormones may all be involved in the dynamic mechanisms of nutrient metabolism. In addition, potential intra-islet paracrine effects are identified.

Animals↗