Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:034761 (insulin)
 211,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isolated rat lung cell suspensions were prepared by collagenase digestion of the lung stroma. These cells were functionally competent as judged, among other criteria, by their constant rates of oxygen uptake and glucose utilization. An important metabolic feature of these cells is that they display very high glycolytic rates. At least 60% of the glucose utilized was converted to lactate, regardless of the glucose concentration in the medium. The state of reduction of the nicotinamide system, as indicated by the lactate-to-pyruvate ratio, was normal, thus indicating that the high glycolytic fluxes are not related to poor oxygenation of the preparation. Utilization of glucose displayed Michaelis-Menten saturation type kinetics with a Vmax of 331 nmol/10(6) cells per h and an apparent Km of 2.4 mM. These values were not affected by the presence of ouabain (0.1 mM), mannoheptulose (5 mM), or insulin (1 mU/ml), whereas phloridzin produced a drastic inhibition of glucose utilzation showing an apparent Ki of 0.4 mM. The substitution of sodium by K+ or Li+ as the predominant cations in the incubation medium does not alter rates of glucose utilization. Optimal pH for glucose utilization was within the physiological range with a more pronounced inhibitory effect at alkaline pH's. The intracellular concentration glucose was found to be low. This finding, in conjunction with a Q10 (27-37 degrees C) for glucose utilization above 2.0 and the differential effects of D- and L-glucose on production, seems to indicate that a stereospecific glucose transport system exists in lung cells. Several findings point to glucose transport into the lung cells as a probable rate-limiting step for its metabolism:1) the activity of the glycolytic enzymes largely exceeded the observed rate of glucose utilization;2) the decrease in enzyme activity during starvation was not accompanied by a decreased glycolytic flux, suggesting that factors other than enzyme activity, perhaps the supply of fuel, are rate limiting in the overall process of glucose breakdown;3) fructose was able to increase lactate production in the presence of saturating concentrations of glucose. These additive effects of glucose and fructose seem to support the point of view that it is not the glycolytic machinery but the supply of fuel which is rate limiting for glucose utilization by isolated rat lung cells.
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PMID:Metabolic features of isolated rat lung cells. I. Factors controlling glucose utilization. 1 58

Proteolytic activity has been measure in rat skeletal muscle by use of [14C]-hemoglobin as substrate. The activity of the alkaline proteinases increases during starvation and in diabetic state. In streptozotocin-diabetic animals the activity of alkaline proteases increases to 300% over a time of 21 days. Insulin treatment reverses the enhanced enzyme activity to normal level.
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PMID:Insulin effect on proteolytic activities in rat skeletal muscle. 2 34

To evaluate the effect of starvation, oral and i.v. nutriments, and hypothyroidism on the peripheral conversion of thyroxine (T4) to 3,3', 5-triiodothyronine (T3) in the rat and mouse, an in vitro system for assessing T4 conversion to T3 by fresh liver homogenates was used. A 2-day starvation in the rat reduced hepatic T3 generation from T4 by 47% +/- 3.5% (mean +/- SE) in six separate experiments and also impaired the metabolism of 125I-r-T3. Administration of carbohydrate (CHO) and amino acids (P), but not lipid (L), significantly increased T3 generation above values observed in the starved rat. The mean serum glucose concentration was similar in all nutriment-infused groups, but serum insulin was significantly greater in the CHO- and P-infused as compared to the L-infused rats. These findings suggest that CHO and P, but not L, are important modulators of hepatic outer ring thyronine deiodination in the rat, perhaps due to increased intracellular glucose. Hypothyroidism in the rat induced by thyroidectomy and congenital secondary hypothyroidism in the dwarf mouse resulted in a striking decrease in hepatic conversion of T4 to T3. This decrease was restored to normal by the daily s.c. administration of physiologic doses of T4 (1.5 microgram/100 g) or T3 (0.5 microgram/100 g) for 14 days, and was increased above normal following treatment of normal rate with greater than physiologic doses of T4 (3microgram/100 g) or T3 (1 microgram/100g). In vitro hepatic conversion of T4 to T3 is, therefore, dependent upon thyroid function. Since 2-days starvation in the rat was associated with decreased serum concentrations of T4, T3, and TSH, and hypothyroidism resulted in decreased conversion of T4 to T3, the effect of a constant 2-day infusion of physiologic doses of T4 or T3 in the starved rat on the in vitro deiodination of T4 was assessed. Thyroid hormone replacement did not enhance the conversion of T4 to T3 in the starved rat. These observations suggest that the starvation-induced decrease in hepatic generation of T3 from T4 is not due to hypothyroidism and that the mechanism(s) of the decreased T3 production observed in starvation and hypothyroidism is different.
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PMID:Effect of starvation, nutriment replacement, and hypothyroidism on in vitro hepatic T4 to T3 conversion in the rat. 3 20

Incorporation of D-3-hydroxy[3-14C]butyrate into lipid in vivo suggests that lactating mammary gland is a major site of ketone-body utilization. The incorporation decreases in short-term insulin deficiency (2h) and on starvation (24h), but increases again on refeeding (2h). The activity of cytosolic acetoacetyl-CoA synthetase parallels the changes in nutritional state, but is not affected by short-term insulin deficiency.
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PMID:Utlization of D-3-hydroxy[3-14C]butyrate for lipogenesis in vivo in lactating rat mammary gland. 3 71

Factors contributing to modifications in the capability for enzyme adaptation as an expression of aging are reviewed. Specific examples of altered enzyme adaptations during aging include the responses of hepatic glucokinase activity to glucose and hepatic tyrosine aminotransferase activity to starvation in Sprague-Dawley rats. These impaired enzyme adaptations apparently are not the consequence of alterations in hepatic function during aging. Instead, they reflect disturbances in extrahepatic hormonal regulatory mechanisms. Specific examples include modifications in the control of circulating levels of insulin glucagon, corticosteroids, and thyroid hormones. Age-dependent changes in the regulation of circulating levels of insulin probably originate within the impaired ability of pancreatic islets of Langerhans to secrete the hormone in response to glucose. The rationale for exploiting this experimental approach as a means to understand biological aging is discussed.
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PMID:Loss of adaptive mechanisms during aging. 3 73

Rat liver glucose 6-phosphate dehydrogenase (G6PD) and malic enzyme (ME) activities were increased by starvation-refeeding to levels above those found in rats fed ad libitum. The increases in enzyme activities above ad libitum-fed levels were prevented by 8-azaguanine and 6-azauridine, but not by 2-azauridine. Blood insulin levels were not affected at the time studied. Two aza analogs, 8-azaadenine and 5-azacytidine, proved to be too toxic in this type of studies. Since 8-azahypoxanthine, 8-azaxanthine and 5-azauracil were neither effective in preventing the enzyme overshoot, nor toxic to the animals, it was concluded that the toxiciyty to the animals of 8-azaadenine and 5-azacytidine is due to the compounds themselves rather than to the breakdown products.
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PMID:Effect of aza-substituted nucleotides on the starve-refeed response of rats. 4 59

Experiments conducted on female Wistar rats showed that 24 hours after the injury of the ventromedial nuclei of the hypothalamus (VMNH) without animal starvation there occurred a slight reduction of insulin in the islets and a significant elevation of the blood immunoreactive insulin (IRI) level, without any glycemia reduction. In animals with intact VMNH glybenclamide produced no changes in the insulin depot in the pancreatic cells, but somewhat increased the IRI level. However, after the VMNH injury glybenclamide caused a sharp insulin depletion in the islets, and a marked elevation of IRI and a decrease of sugar in the blood.
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PMID:[Insulin secretion in rats after hypothalamic damage]. 11 44

Two or more melanotropic peptides are present in extrahypophyseal regions of mammalian brain. Previous studies showed that extrahypophyseal melanotropic activity is not influenced by hypophysectomy, adrenalectomy, or exogenous glucocorticoid. The present study investigated the possible influence of the following factors on the level of melanotropic activity in whole brain, cerebral cortex, cerebellum, midbrain, and brainstem of mouse and rat: age, sex, starvation; and of the following hormones or drugs administered by the intraperitoneal or intracerebral route: norepinephrine, dihydroxyphenylalanine, pargyline, 6-hydroxy-dopamine, alpha-methyltyrosine methyl ester, reserpine, acetylcholine, pilocarpine, atropine, serotonin, p-chlorophenylalanine, pentobarbital, pentylenetetrazol, insulin, melatonin, and cycloheximide. Only age influenced extrahypophyseal melanotropic activity. The activity per unit of tissue wet weight or of tissue protein increased in all regions progressively from birth to 1 yr of age. Extrahypophyseal melanotropic activities perunit wet weight of tissue at 50 wk averaged 4.3 times those at birth. When brain of adult rodents was fractionated by differential centrifugation, the major proportion of melanotropic activity was recovered in myelin (27-35 percent), nerve endings (20-22 percent), and mitochondria (25-30 percent). The lower activity in newborn brain resulted not onlyfrom absence of a myelin fraction, but also from lower activity at birth in nerve endings and mitochondria.
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PMID:Melanotropic activity in extrahypophyseal regions of rodent brain: effect of age, hormones, and drugs. 12 36

1. The regulation of glucose uptake and disposition in skeletal muscle was studied in the isolated perfused rat hindquarter. 2. Insulin and exercise, induced by sciatic-nerve stimulation, enhanced glucose uptake about tenfold in fed and starved rats, but were without effect in rats with diabetic ketoacidosis. 3. At rest, the oxidation of lactate (0.44 mumol/min per 30 g muscle in fed rats) was decreased by 75% in both starved and diabetic rats, whereas the release of alanine and lactate (0.41 and 1.35 mumol/min per 30 g respectively in the fed state) was increased. Glycolysis, defined as the sum of lactate+alanine release and lactate oxidation, was not decreased in either starvation or diabetes. 4. In all groups, exercise tripled O2 consumption (from approximately 8 to approximately 25 mumol/min per 30 g of muscle) and increased the release and oxidation of lactate five- to ten-fold. The differences in lactate release between fed, starved and diabetic rats observed at rest were no longer apparent; however, lactate oxidation was still several times greater in the fed group. 5. Perfusion of the hindquarter of a fed rat with palmitate, octanoate or acetoacetate did not alter glucose uptake or lactate release in either resting or exercising muslce; however, lactate oxidation was significantly inhibited by acetoacetate, which also increased the intracellular concentration of acetyl-CoA. 6. The data suggest that neither that neither glycolysis nor the capacity for glucose transport are inhbitied in the perfused hindquarter during starvation or perfusion with fatty acids or ketone bodies. On the other hand, lactate oxidation is inhibited, suggesting diminished activity of pyruvate dehydrogenase. 7. Differences in the regulation of glucose metabolism in heart and skeletal muscle and the role of the glucose/fatty acid cycle in each tissue are discussed.
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PMID:Glucose metabolism in perfused skeletal muscle. Effects of starvation, diabetes, fatty acids, acetoacetate, insulin and exercise on glucose uptake and disposition. 13 49

Experiments designed to determine whether the role of glucocorticoid (GC) in the induction of the enzyme overshoot response to starvation-refeeding was direct or permissive through insulin were conducted. Intact, adrenalectomized (ADX), and streptozotocin (STREP) treated rats with or without insulin and/or GC replacements were starved for 48 hours and refed a 65% glucose diet for 48 hours. The typical enzyme overshoot response to starvation-refeeding was observed in the intact rats, ADX rats given GC, STREP rats given insulin and ADX-STREP rats given glucocorticoid plus insulin. No overshoot was observed if glucocorticoid was absent whereas a modest increase in enzyme activity could be observed in insulin deficient rats treated with GC.
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PMID:Interaction of glucocorticoid and insulin in the responses of rats to starvation-refeeding. 15 37


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