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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic effects of acute (4 h) and prolonged (24 h) growth hormone excess at pathophysiological concentrations were studied by growth hormone administration to normal subjects with and without somatostatin induced insulin deficiency. Acute growth hormone excess produced mild hyperinsulinaemia, but blood glucose concentrations were unaltered whereas chronic growth hormone excess caused a small (0.5 mmol/l) but significant rise in overnight-fasting blood glucose concentration together with a similar rise in fasting insulin levels (Mean +/- SEM 9 +/- 1 v 4 +/- 1 mU/l, p less than 0.01). When insulin secretion was suppressed by somatostatin, a hyperglycaemic effect of acute growth hormone excess was unmasked, and the hyperglycaemic effect of chronic growth hormone excess was exaggerated. Acute growth hormone administration without somatostatin had a mild ketogenic action despite stimulated insulin secretion but no change in plasma non-esterified fatty acid or blood glycerol levels was observed. Somatostatin magnified the ketogenic effect of acute growth hormone excess, and unmasked a lipolytic action. Prolonged growth hormone excess had a lipolytic action that was increased by somatostatin, although the ketogenic effect of growth hormone was only seen during somatostatin induced insulin deficiency. The acute hyperglycaemic, lipolytic and ketogenic actions of growth hormone in normal subjects are limited by a compensatory rise in insulin secretion although with chronic exposure hyperglycaemic and lipolytic effects are seen. In insulin-deficient states, however, elevated growth hormone levels could be important in promoting hyperglycaemia and hyperketonaemia.
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PMID:Metabolic effects of acute and prolonged growth hormone excess in normal and insulin-deficient man. 611 Jun 6

We have investigated in normal subjects the possible role of plasma free fatty acids (FFA) and blood ketone bodies (KB) in the regulation of human somatostatin secretion. Heparin injected during the intravenous infusion of a fat emulsion raised FFA levels acutely from 0.4 +/- 0.1 to near 3 mmol/L. Plasma somatostatin-like immunoreactivity (SLI) rose from a mean (+/- SEM) basal value of 9.2 +/- 1.0 ng Eq S14/L to 20.0 +/- 6.0 ng Eq S14/L (P less than 0.05). Plasma immunoreactive insulin (IRI) level was unchanged and glucagon (IRG) concentration decreased from 156 +/- 20 to 107 +/- 2 ng/L (P less than 0.05). During this test, there was a rise not only in FFA but also in plasma triglycerides (TG) and in blood glycerol and KB levels. The infusion of a fat emulsion alone increased triglyceride and glycerol levels to a similar extent but induced also a mild rise of FFA (0.37 +/- 0.05 to 1.13 +/- 0.5 mmol/L, P less than 0.01), KB (78 +/- 12 to 360 +/- 45 mumol/L, P less than 0.01), and SLI (14.8 +/- 4.6 to 23.8 +/- 7.1 ng Eq S14/L, P less than 0.05). The induction by DL-Na-3-hydroxybutyrate infusion of a rise of KB was associated with a decrease of FFA (P less than 0.05) and SLI (P less than 0.05) without modification of IRI or IRG levels. Phentolamine infusion did not modify the SLI or glucagon response to acute elevations of FFA, whereas propranolol suppressed the increase of SLI without preventing the concomitant decrease of IRG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of somatostatin secretion in man: study of the role of free fatty acids and ketone bodies. 614 47

Several methods of purification of Na+,K+-adenosine triphosphatase (ATPase) have been previously described for a wide variety of tissues. In general, highest activity preparations have necessitated large amounts of tissue and many purification steps. This article describes a technique that allows partial purification of Na+,K+-ATPase from as few as 15 rat brains and should be of interest to investigators of the pharmacology of this particular enzyme system. In this modified version of the Jorgensen procedure (Biochim Biophys Acta 356:36--52, 1974) we purified the Na+,K+-ATPase from 15--90 rat brains, and obtained enzyme preparations with a mean specific activity of 552 +/- 37.6 mumol Pi/mg of protein/hr (95.5% ouabain sensitive). This "purified" enzyme had an activity ratio (Mg2+ + Na+ + K+)/(Mg2+ + Na+) of 47.4 +/- 12.3 SEM, compared to 3.29 +/- 0.17 SEM for the untreated microsomes. Ouabain inhibited the "purified" enzyme with an I50 of 6 X 10(-9) M. Ouabain binding (644 pmol/mg of protein) yielded a turnover number of 13,700 min-1. Sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis of the enzyme revealed predominantly the alpha and beta subunits with some minor contaminant bands. Previous methods of purification of rat brain Na+,K+-ATPase have employed sodium deoxycholate and high concentrations of NaI; the reported specific activity obtained was generally 150--350 mumol Pi/mg of protein/hr. We have employed higher SDS concentrations than in Jorgensen's technique for rabbit kidney but the procedure is simpler because sucrose gradients are not used. Final wash steps also include 10--20% glycerol in the media. These modifications have yielded Na+,K+-ATPase of significantly higher specific activity than previously reported for rat brain.
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PMID:A simple method for the purification of rat brain Na+,K+-adenosine triphosphatase (ATPase). 628 10

In order to evaluate the effects of moderate alcohol intake on intermediate metabolites, five normal subjects and five euglycemic insulin-dependent diabetics (IDDM) were administered two different isocaloric diets; in one diet 35% of the caloric intake consisted of red wine. The insulin-dependent diabetics were connected to an artificial endocrine pancreas (AEP), and glucose levels were continuously monitored. Blood lactate, pyruvate, acetoacetate (AcAc), 3-hydroxybutyrate (3-OHB), glycerol, free fatty acids (FFA), and alanine levels were measured over a 15-hour period from 9 AM to 12 PM. The results showed that alcohol intake did not significantly influence the glucose profiles in either group (111 +/- 4 mg/100 ml versus 110 +/- 4 mg/100 ml for IDDM; 72 +/- 2 mg/100 ml versus 82 +/- 3 mg/100 ml for controls, 15-hour mean +/- SEM), but in both groups it induced a marked increased in the levels of lactate (1.115 +/- 0.067 mM/liter with alcohol versus 0.706 +/- 0.031 mM/liter without alcohol for IDDM; 0.847 +/- 0.052 mM/liter with alcohol versus 0.666 +/- 0.035 mM/liter without alcohol for controls), in the lactate/pyruvate ratio (24.04 +/- 2.12 with alcohol versus 11.42 +/- 0.20 without alcohol for IDDM; 20.84 +/- 2.16 with alcohol versus 11.62 +/- 0.27 without alcohol for controls), in the levels of 3-OHB (0.081 +/- 0.007 mM/liter with alcohol versus 0.046 +/- 0.003 mM/liter without alcohol for IDDM; 0.067 +/- 0.007 mM/liter with alcohol versus 0.025 +/- 0.002 mM/liter without alcohol for controls) and in the 3-OHB/AcAc ratio (1.452 +/- 0.153 with alcohol versus 0.599 +/- 0.036 without alcohol for IDDM; 1.723 +/- 0.198 with alcohol versus 0.439 +/- 0.040 without alcohol for controls) because of a more reduced redox state. Alcohol intake during meals depressed alanine concentration, while glycerol levels showed a transient increase. Reduced blood FFA concentrations after alcohol intake were observed only in controls. This study demonstrates that moderate alcohol intake with meals also affects intermediate metabolites despite euglycemia. These effects were similar both in normal subjects and in IDDM, even if the harmful effects of alcohol may be enhanced by poor metabolic control in the latter.
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PMID:Metabolic effects of moderate alcohol intake with meals in insulin-dependent diabetics controlled by artificial endocrine pancreas (AEP) and in normal subjects. 634 61

Subcutaneous insulin pumps deliver insulin both as a premeal bolus and as a continuous basal rate. It has been shown that the effect of the basal component is primarily to maintain normoglycemia overnight, but it is not known whether an intermittent pulsed infusion would achieve similar metabolic control. Six type I diabetic subjects (19-31 yr) were studied for 2 wk. Glycemic control was maintained by premeal injections of regular insulin with subcutaneous infusion overnight. A constant basal flow rate of insulin was delivered either continuously or intermittently as pulses spaced at 30-, 60-, and 120-min intervals. With each type of infusion, given in a randomized order, plasma glucose levels at 0600 h were: 81 +/- 12, 89 +/- 11, 102 +/- 14, and 94 +/- 13 mg/dl (mean +/- SEM), respectively. These values are not significantly different and remained stable until 1000 h. In addition, the hormonal responses (immunoreactive glucagon and "free" insulin levels) and metabolite levels (lactate, pyruvate, 3-hydroxybutyrate, alanine, and glycerol) were the same with continuous and pulsed insulin. These findings are in keeping with the expected kinetics for subcutaneously injected insulin. They may be of considerable interest for the design of smaller and more efficient subcutaneous insulin infusion pumps and demonstrate the wide physiologic limits for subcutaneous basal insulin replacement.
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PMID:Overnight metabolic control with pulsed intermittent versus continuous subcutaneous insulin infusion. 635 9

This study examined the effect of an aldose reductase inhibitor (Sorbinil, CP 45634, Pfizer, Sandwich, Kent, United Kingdom) on the metabolite profile of the lens during the first week after induction of diabetes with alloxan. The lens content of sorbitol, fructose, glycerol 3-phosphate, and glucose 6-phosphate was, respectively, 0.33 +/- 0.03, 0.55 +/- 0.05, 0.10 +/- 0.01, and 0.074 +/- 0.006 mumol/g (means +/- SEM) in the control group rising to 12.2 +/- 0.52, 3.20 +/- 0.10, 0.76 +/- 0.10, and 0.200 +/- 0.009 in lenses from alloxan-diabetic rats. Sorbinil treatment (40 mg/kg) decreased the lens content of sorbitol to 0.60 +/- 0.06, fructose to 0.85 +/- 0.08, and glycerol 3-phosphate to 0.36 +/- 0.03 mumol/g; glucose 6-phosphate remained unchanged. Significantly, the lens content of glutathione was decreased to 60% of the normal value in the diabetic group, but was sustained at normal levels with Sorbinil treatment. The ATP content of the lens was not altered by diabetes or Sorbinil treatment at this time interval. Sorbinil has no significant effect on the above metabolites in the normal rat lens. The effect of Sorbinil in restoring normal levels of glutathione and glycerol 3-phosphate may be a potentially important facet of the action of this drug. The interlocking of metabolic pathways by the redox state of NAD+/NADH and NADP+/NADPH, their derangement in diabetes, and the wider effects of Sorbinil on the network of reactions in the lens are discussed.
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PMID:The effect of an aldose reductase inhibitor (Sorbinil) on the level of metabolites in lenses of diabetic rats. 640 81

Circulating hormone and metabolite profiles have been studied in ten patients with alcoholic cirrhosis, five patients with alcoholic hepatitis and/or fatty liver, and nine normal controls over a 12-h period of meals and activity. Blood glucose was elevated throughout the day in both cirrhotic and non-cirrhotic alcoholics (mean 12-h glucose; controls 5.38 +/- 0.16 (SEM) mmol/l; cirrhotics 6.98 +/- 0.30 mmol/l, P less than 0.001; non-cirrhotics 7.18 +/- 0.26 mmol/l, P less than 0.001). Non-cirrhotic alcoholics had an exaggerated insulin response to meals, whereas cirrhotic patients had hyperinsulinaemia throughout the day (mean 12-h insulin; controls 16.3 +/- 2.3 mU/l; cirrhotics 35.8 +/- 6.6 mU/l, P less than 0.02). Growth hormone levels were elevated only in patients with cirrhosis (mean 12-h growth hormone, 7.06 +/- 1.35 v. 0.85 +/- 0.17 micrograms/l, P less than 0.001). Serum cortisol was persistently elevated in cirrhotics but only in the evening in non-cirrhotic alcoholics. Lactate and pyruvate responses to meals were exaggerated in non-cirrhotic patients whereas in cirrhotics, levels were persistently raised. Blood glycerol was elevated in all alcoholic patients whereas ketone body levels were normal. Hypertriglyceridaemia was observed only in non-cirrhotic patients. No relationship between the endocrine and metabolic state was observed in either cirrhotic or non-cirrhotic patients.
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PMID:Hormone and metabolite profiles in alcoholic liver disease. 641 54

We have previously reported that normal Wistar rats fed an isocaloric, sucrose-rich (63%) diet (SRD) developed glucose intolerance and elevated triglyceride levels in plasma as well as in heart and liver tissue. This metabolic state was accompanied by hyperinsulinism both in vivo and in vitro, suggesting that a state of insulin resistance has developed. The aim of this study was to gather information on the various plasma post-heparin lipolytic activities in rats fed a SRD. Hepatic triglyceride lipase (H-TGL) was evaluated by both, protamine sulfate inhibition (PSI) of extrahepatic lipoprotein lipase (LPL) and heparin-Sepharose affinity chromatography (H-SAC). Both methods rendered comparable results. Total triglyceride lipase (T-TGL) was measured after Krauss et al. and monoglyceride hydrolase (MGH) after Vogel et al. Our results have shown a significant decline of plasma T-TGL (5.32 +/- 0.34 means +/- SEM vs. 7.48 +/- 0.64 mumol glycerol ml-1 h-1; p less than 0.01), H-TGL (3.71 +/- 0.28 vs. 5.05 +/- 0.69; p less than 0.05), LPL (1.61 +/- 0.26 vs. 2.42 +/- 0.41; p less than 0.05) and MGH (558 +/- 108 mumol glycerol l-1 min-1 vs. 1,165 +/- 45; p less than 0.001) activities. Thus, feeding a sucrose-rich diet induced a state of hyperlipemia and insulin resistance in which not only plasma T-TGL but also H-TGL and MGH activities were significantly decreased. This suggests that the latter two enzymes are also under nutritional and/or hormonal control.
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PMID:Post-heparin plasma hepatic triglyceride lipase and monoglyceride hydrolase activities in hyperlipemia induced by a sucrose rich diet. 661 28

A variety of assays are available for measuring platelet-associated IgG (PAIgG) but the complexity of these assays increases the potential for technical errors. These errors are difficult to detect and, if possible, known positive and negative control platelets should be included with each run. However, patient platelets with elevated levels of IgG are seldom available. This report describes a method for producing positive control platelets that can be labeled with differing amounts of IgG. Normal serum IgG (Cohn fraction II) was incubated with washed 2 percent formalin-fixed platelets for 60 minutes at 37 degrees C. The amount of IgG on the platelets was proportional to the concentration of soluble IgG and the number of incubations. Normal platelet IgG levels were 1.2 +/- 0.1 fg per platelet (mean +/- SEM, n = 34) and positive control platelets had 4.6 +/- 0.2 (n = 12) or 8.4 +/- 0.4 (n = 7). There was no change in the level of PAIgG when stored at 4 degrees C for 1 week, although there was a 28 percent loss in recoverable platelets. When mixed 1:1 with 60 percent glycerol and stored at -70 degrees C, the level of PAIgG was stable for 3 months, with less than 12 percent platelet loss on recovery (n = 12). These positive control platelets have proved useful for monitoring assay performance.
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PMID:The production of platelet controls for assays quantitating platelet-associated IgG. 664 29

This investigation intended to clarify the effects of malnutrition in utero on enzymes of glycerol metabolism and the stores of phosphorylated glycerol intermediates in liver, striated muscle, and brain in the rat. Pregnant Wistar rats were restricted to an intake of 50% (M) of ad libitum fed controls (C) from the seventh day of gestation onward. Fetuses were removed 2 days (-2), or 1 day (-1), before term, or at the day of birth (DOB) The M fetuses and newborn rats were stunted. Their hepatic alpha-glycerophosphate oxidase (GPO) levels were lower than those of C in utero (mean +/- SEM: M = 23.1 +/- 1.5, 15.8 +/- 1.1, and 31.6 +/- 4.5; C = 34.8 +/- 4.9, 39.8 +/- 7.0, and 23.6 +/- 5.0 nmol/min X cm at -2, -1, and DOB, respectively; F = 7.29 [1,57], P less than .01). In muscle, this enzyme, as well as liver and brain alpha-glycerophosphate dehydrogenase (GPD), alpha-glycerophosphate (GP), and dihydroxyacetone phosphate (DHAP), only varied with the developmental stage. Although the latter was a significant differential factor in all the determinations, maternal diet only affected brain DHAP stores (M = 1.85 +/- 0.36, 1.03 +/- 0.16, 0.74 +/- 0.10; C = 2.33 +/- 0.46, 1.87 +/- 0.21, 1.13 +/- 0.18 mumol/g at -2, -1, and DOB, respectively; F = 9.03 [1,53], P less than .01). These findings support the contention that intrauterine malnutrition can alter normal ontogenesis of glycerol metabolism enzymes in certain organs and become a negative factor disturbing normal gluconeogenesis and glycogenolysis, with potential disruption of energy homeostasis immediately after birth.
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PMID:Intrauterine malnutrition in the rat: alterations of fetal glycerol metabolism. 665 62


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