Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastric inhibitory polypeptide (GIP) has insulinotropic actions in the presence of hyperglycemia. However, its extrapancreatic effects on glucose homeostasis are controversial. We have studied the relationships between GIP and immunoreactive insulin (IRI) and glucose turnover rates (D3H-3 glucose technique) in five poorly controlled type II diabetic patients and five normal subjects before and after a breakfast containing 500 kcal including 42 g sucrose. Mean fasting serum glucose levels and glucose responses were significantly (P less than 0.001) higher in the diabetic patients than in normal subjects. Mean basal serum IRI levels were similar in both groups [12.8 +/- 2.9 (SEM) vs. 11.8 +/- 2 microU/ml, P = NS]. After meal ingestion, mean IRI levels rose significantly to a peak at 20 min in the normal subjects but the responses were blunted in the diabetic patients (74 +/- 10 vs. 24 +/- 6 microU/ml, P less than 0.001). At all other times studied (60-180 min), mean serum IRI levels were similar in the diabetic patients and the normal subjects except at 180 min. Mean basal serum GIP levels were similar in the diabetic patients and the normal subjects (538 +/- 100 vs. 400 +/- 50 pg/ml, P = NS). After meal ingestion, mean GIP levels rose between 0-60 min but were significantly higher in the diabetic patients only at 20 min (1200 +/- 190 vs. 566 +/- 76 pg/ml, P less than 0.01). Mean basal hepatic glucose output was higher (P less than 0.01) in the diabetic patients. However, the mean basal MCR values were similar. After meal ingestion, total splanchnic glucose output and rates of glucose utilization (RU) were significantly higher in the diabetic patients compared with the normal subjects (P less than 0.001, and P less than 0.001, respectively). Postmeal MCR values were not statistically different in both groups. There were significant positive correlations between postmeal splanchnic glucose output and both IRI (r = 0.805, P less than 0.005) and GIP (r = 0.749, P less than 0.02) in the diabetic patients but not in the normal subjects (r = 0.10, P = NS for both). Whereas no relationships existed between RU and IRI in either group, RU correlated strongly with GIP (r = 0.810, P less than 0.005) only in the diabetic patients. We hypothesize that GIP may play a compensatory role to improve both impaired beta-cell insulin release and peripheral glucose utilization which are the recognized pathogenetic mechanisms underlying type II diabetes mellitus.
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PMID:Gastric inhibitory polypeptide responses and glucose turnover rates after natural meals in type II diabetic patients. 351 Feb 24

The effect of insulin on glucose uptake, transfer, and metabolism was investigated in the human placenta perfused in vitro. Insulin concentrations in maternal perfusion medium were varied from 0-1200 microU/ml, whereas the glucose concentration was kept constant in maternal and fetal perfusion media. Despite significant uptake of insulin by the perfused placenta, neither glucose uptake and transfer nor lactate release were significantly modified during a 1-h insulin perfusion. The MCR of insulin by the placenta was 0.29 +/- 0.03 (+/- SEM) ml/min X g at physiological insulin levels. These data suggest that placental glucose transport and metabolism are insensitive to maternal plasma insulin variations and that the low clearance rate of insulin by the placenta is not a major determinant of maternal insulin adjustments during pregnancy.
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PMID:Effect of insulin on glucose uptake and metabolism in the human placenta. 351 49

Previous estimates of PRL pharmacokinetics have been made using radioiodinated human PRL (hPRL) infusions or by measuring serum PRL disappearance following prolactinoma resection. The recent purification of hPRL in significant quantities made it possible to measure the clearance and volume of distribution directly. Studies were also carried out to determine absorption and clearance after im injection. In five normal men whose endogenous PRL secretion was suppressed by dopamine, a loading dose of hPRL (70-90 micrograms) followed by a constant infusion (1.39-2.9 ng/min) produced steady state serum PRL levels of 15.2-25.4 ng/mL by 30-60 min. The calculated mean volume of distribution was 7.3 +/- 2.9 (+/- SD) L. The calculated MCR was 71 +/- 19 mL/min X m2, and the calculated production rate was 802 +/- 377 micrograms/24 h X m2. The plasma disappearance half-life following discontinuation of the infusion was 37 +/- 10 min. The PRL infusate consisted primarily (75.6%) of a 22.5 K dalton species, probably PRL monomer, a component eluting at 45K daltons (16.1% of the total radioimmunoreactivity), probably dimer, and a small amount of a larger mol wt species. Serum obtained during dopamine infusion but before hPRL infusion contained 68.1% of the 22.5K, 7.2% of the 45K, and 24.7% of the larger mol wt moieties. During hPRL infusion in two men there was a relative decrease in the proportion of PRL monomer to 55% and 69% and a relative increase in the PRL dimer to 33% and 18%, respectively. hPRL was injected im in doses of 1, 2, 4, and 8 micrograms/kg without prior dopamine infusion. No significant changes in serum PRL levels occurred after the 1 and 2 micrograms/kg doses (n = 5). After the 4 micrograms/kg dose (n = 8), mean serum PRL levels rose from 10.0 +/- 1.8 (+/- SEM) ng/mL to peak levels of 13.1 +/- 1.8 ng/mL (P less than 0.01). After the 8 micrograms/kg dose (n = 7), PRL levels rose from 9.3 +/- 1.6 to 16.5 +/- 1.8 ng/mL (P less than 0.01). The PRL rise began between 60 and 80 min after injection; peak levels occurred at 160-180 min. In two men given 8 micrograms/kg who were sampled for an additional 3 h, PRL levels peaked at 200-220 min and began to fall by 220-240 min, but had not returned to baseline by 6 h. There were no side-effects of PRL administration, although the 8 micrograms/kg dose caused transient local discomfort.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacokinetic studies of highly purified human prolactin in normal human subjects. 359 9

The validity of C-peptide as a peripheral marker of insulin secretion during different physiological conditions depends on the demonstration that C-peptide clearance is constant under these circumstances. Recently biosynthetic human C-peptide, identical in structure to pancreatic human C-peptide, became available for use in human subjects. The present study was undertaken to determine if the metabolic clearance of C-peptide was altered by ingestion of a mixed meal. Eight insulin-dependent diabetic patients received constant iv infusions of biosynthetic human C-peptide which raised the plasma C-peptide concentration to a level of 3.8 +/- 0.2 (+/- SEM) pmol/ml. The MCR of C-peptide was 4.5 +/- 0.3 ml/kg X min. After steady state levels of C-peptide had been reached, each patient consumed a 530 calorie mixed meal. The plasma glucose concentration increased from a baseline value of 104.5 +/- 4.8 mg/dl to a 336 +/- 10 mg/dl 150 min later. This change in plasma glucose was not associated with a significant alteration in the plasma C-peptide concentration and the MCR of the infused C-peptide was not affected by meal ingestion (4.5 +/- 0.3 vs. 4.3 +/- 0.3 ml/kg X min). These results therefore support the validity of using C-peptide as a marker for changes in insulin secretion after mixed meals.
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PMID:Ingestion of a mixed meal does not affect the metabolic clearance rate of biosynthetic human C-peptide. 372 29

Peptide YY (PYY) is a 36 amino acid peptide produced by mucosal endocrine cells of the ileum and colon which inhibits acid secretion and intestinal transit in man. To assess its effects on metabolites and digestive hormones PYY was infused into 18 fasting normal subjects at three dose levels (0.06, 0.19, and 0.57 pmol kg-1 min-1), each for a period of 1 h. During the infusions mean plasma PYY levels increased by 8, 25, and 73 pmol/liter, respectively. The mean disappearance half-time on stopping the infusions was 9.2 +/- 0.4 (SEM) min. The mean MCR was 7.3 +/- 0.7 ml kg-1 min-1 and the apparent volume of distribution was calculated to be 94 +/- 9 ml kg-1. During the highest dose infusion there was a significant increase in both systolic and diastolic blood pressure, of 8.6 +/- 3.7 mmHg (P less than 0.05) and 10.9 +/- 3.0 mmHg (P less than 0.01), respectively. PYY caused a significant 50% reduction in plasma pancreatic polypeptide concentrations (P less than 0.05) and a 55% reduction in circulating motilin levels (P less than 0.05). PYY had no significant effect on circulating concentrations of insulin, glucagon, gastrin, gastric inhibitory peptide, neurotensin, enteroglucagon, or vasoactive intestinal peptide. PYY also had no significant effect on circulating concentrations of glucose, lactate, glycerol, or nonesterified fatty acids. This recently discovered human intestinal hormonal peptide thus has significant effects both on gastrointestinal hormones (motilin and pancreatic polypeptide) and blood pressure in man, but appears not to influence glucose or lipid metabolism.
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PMID:Peptide YY kinetics and effects on blood pressure and circulating pancreatic and gastrointestinal hormones and metabolites in man. 375 28

Synthetic oxytocin (OT) was infused iv in four men at 3 mU/min, and the rate was doubled every 90 min for a total of three infusion periods. The mean (+/- SEM) OT MCR was 16.4 +/- 1.7 ml/kg X min and was independent of the rate of infusion. A method for measuring OT in urine was developed using an octadecasilyl-silica column for extraction of the hormone. The extracted residue was reconstituted in potassium phosphate buffer, pH 7.4, for RIA. The minimum detectable level of OT in urine was 0.2 microU/ml (defined as a bound to free ratio of approximately 90%). The mean recovery of OT was 77 +/- 2%. The mean (+/- SEM) concentration of endogenous OT in urine was 10.2 +/- 1.4 microU/ml. Endogenous OT in urine eluted from a reverse phase high pressure liquid chromatography column as a single peak of OT immunoreactivity in the position of synthetic OT. Urinary OT excretion during infusion of synthetic OT was linearly correlated with plasma OT concentration whether calculated as microunits of urinary OT per mg creatinine (r = 0.89) or urinary OT per min (r = 0.93). Mean urinary fractional clearance of OT (OT clearance/creatinine clearance) was 3.6% renal clearance of OT (5.5 ml/min or 0.43% of MCR). Thus, OT MCR was constant over a wide range of physiological plasma OT levels and was similar to MCR in pregnant women studied previously in this laboratory. Less than 1% of OT was cleared in urine. This study defines the relationship between urinary and plasma OT during steady state infusion of physiological concentrations of the hormone and indicates that measurements of OT in urine by RIA may prove helpful for pharmacokinetic and physiological studies of OT-related events in humans.
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PMID:Clearance studies of oxytocin in humans using radioimmunoassay measurements of the hormone in plasma and urine. 379 53

Insulin-stimulated glucose disposal was investigated using the euglycemic hyperinsulinemic glucose clamp technique in six women with anorexia nervosa (27.3 +/- 4.9 yr old; weight, 38.8 +/- 6.6 kg) and compared to results obtained in six normal women (22.6 +/- 1.2 yr old; weight, 58 +/- 2.5 kg) and seven obese women (26.8 +/- 7.7 yr old; weight, 92.5 +/- 13.8 kg). The glucose clamp was performed for 2 h using the Biostator and a continuous insulin infusion of 100 mU kg-1 h-1. Plasma levels of insulin were determined at 30-min intervals. Plasma levels of glucagon, FFA, glycerol, 3-hydroxy-butyrate, and alanine were measured basally. Blood glucose levels were similar in normal subjects and anorectic patients; they were slightly but significantly higher in the obese patients. The indices of insulin sensitivity measured were the MCR of glucose and the ratio of glucose infused to insulin infused (G/I). They were very similar in anorectic subjects [MCR, 13.5 +/- 2.4 (+/- SEM) ml kg-1 min-1; G/I, 5.2 +/- 0.9 mg/mU) and normal subjects (MCR, 13.5 +/- 1.7 ml kg-1 min-1; G/I, 5.2 +/- 0.4 mg/mU), but were significantly reduced in obese patients (MCR, 5.1 +/- 0.8 ml kg-1 min-1; G/I, 2.6 +/- 0.3 mg/mU; P less than 0.0025). Differences in plasma insulin among the three groups were not statistically significant. Plasma alanine levels were higher in anorectic than in normal or obese subjects, suggesting defective gluconeogenesis. Thus, insulin-stimulated glucose disposal is normal in patients with anorexia nervosa, a finding that contrasts with the previously reported increase in erythrocyte insulin receptors in this disease.
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PMID:Insulin-stimulated glucose disposal is not increased in anorexia nervosa. 388 Jul 68

Circulating sex hormone-binding globulin (SHBG) binding capacity and percent free estradiol (% free E2) were measured in separate groups of female rhesus monkeys from 2 months of age through adulthood (greater than 4.5 yr old). The SHBG concentration alone was also measured in 11 adult and 6 sexually immature animals on the same day as the blood MCR of E2. Serum SHBG levels were the highest (range, 12-25 micrograms T/dl) and the % free E2 the lowest (0.88%) in animals 6 months old or less. After the age, serum SHBG binding capacity declined generally at an average rate of 0.11 SHBG U (microgram T/dl)/month toward a nadir in adulthood. There was no difference in the SHBG levels in the follicular or luteal phase of the menstrual cycle. The relative blood MCR E2 and circulating SHBG binding capacity were significantly greater (P less than 0.001) in the sexually immature animals [MCR E2, 48.4 +/- 5.2 (SEM) liters/day . kg body wt; SHBG, 9.8 +/- 1.0 microgram T/dl, n = 6] than in adult animals (MCR E2, 27.7 +/- 1.7 liters/day kg body wt; SHBG, 4.6 +/- 0.3 microgram T/dl, n = 11). There was no relation between the MCR E2 and circulating SHBG levels within each group of adult or immature animals. The mean % free E2 doubled (to 1.6%) between 1 and 54 months of age; there was no relation between total circulating E2 and % free E2. Although a high SHBG binding capacity and a low % free E2 in the circulation of the immature animal does not inhibit the metabolic clearance of E2; it remains possible that these factors (and others) may hinder the access of E2 to reproductive target tissues and thereby contribute to the slow acquisition of reproductive competence in this species.
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PMID:Changes in sex hormone-binding globulin binding capacity and percent free estradiol during development in the female rhesus monkey (Macaca mulatta): relation to the metabolic clearance rate of estradiol. 403 16

The MCR and t1/2 of D-Trp6 LRH, a potent analog of LRH, were compared to those of exogenous LRH. Studies were performed on eight normal subjects during and after cessation of a constant infusion of D-Trp6 LRH and LRH. The D-Trp6 LRH and LRH were quantitated individually by sensitive and specific RIAs which did not cross-react with the other peptide infused or fragments of the degraded peptides. High performance liquid chromatography of plasma from a patient infused with D-Trp6 LRH alone yielded one peak, which coeluted with D-Trp6 LRH. The kinetics of peptide clearance were biphasic, with a rapid and a slow component of elimination. The t1/2 of the rapid component of D-Trp6 LRH clearance was 18.7 +/- 1.8 (SEM) min. This was significantly longer (P less than 0.001) than the t1/2 for the LRH of 7.8 +/- 1.1 min. The MCRs for D-Trp6 LRH and LRH were 503.4 +/- 196.4 and 1766.6 +/- 404.3 ml/min, respectively (P less than 0.01). The longer t1/2 of D-Trp6 LRH compared to that of LRH reflects the slower clearance, which is probably due to a decreased rate of degradation. These findings indicated that the enhanced bioactivity of D-Trp6 LRH is in part due to a decreased rate of degradation.
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PMID:Metabolic clearance and plasma half-disappearance time of D-TRP6 and exogenous luteinizing hormone-releasing hormone. 621 Jul 6

The autologous mixed lymphocyte reaction (auto-MLR) measures the ability of non-T cells to stimulate autologous T cells to proliferate in tissue culture. The auto-MLR was studied in 11 patients with autoimmune thrombocytopenic purpura (ATP). Seven patients had decreased auto-MLR, which averaged 4440 +/- 3364 cpm (SEM) compared to 15,360 +/- 6905 cpm for simultaneously studied controls. The average of the ratios of cpm incorporated by patients/cpm incorporated by control subjects was 0.20 +/- 0.06 (p less than 0.01). Serum from all 7 patients with low auto-MLR decreased the auto-MLR of normal subjects by an average of 56% +/- 8.5 (p less than 0.001). Preliminary results indicate that the inhibitory effect was mediated by a component of the IgG immunoglobulin fraction of serum. Sera from normal persons and from ATP patients with normal or high auto-MLR did not affect the auto-MLR of normal subjects. It was further shown that non-T cells from 3 of 5 patients with decreased auto-MLR failed to stimulate allogeneic T cells normally. It is concluded that many patients with ATP have decreased auto-MLR apparently due to the presence of a serum blocking factor and, perhaps, a defective stimulatory capacity of non-T-cells.
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PMID:Abnormal autologous mixed lymphocyte reaction in autoimmune thrombocytopenic purpura. 645 39


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