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)

Extracts of fasted rat diaphragms, previously treated with or without insulin were assayed for glycogen synthase, protein kinase and cyclic [3H]-AMP binding. Treatment with insulin produced an elevation in the % of glycogen synthase I and a concurrent decrease in cyclic AMP-dependent protein kinase activity and cyclic [3H]-AMP binding. Analysis of extracts by disc gel electrophoresis demonstrated the inhibition of cyclic [3H]-AMP binding to involve the Type I protein kinase holoenzyme. Inhibition of protein kinase activity was most apparent in the presence of 0.2 micrometer cyclic AMP, with enzymatic activity of the insulin-treated extracts typically 60--65% of control. Higher assay concentrations diminished the difference between control and insulin-treated extracts and concentrations greater than 20 micrometer abolished it. The inhibition of cyclic AMP-dependent protein kinase activity after insulin was a transient and labile phenomenon. The effect was independent of ATP concentration in the assay, but was sensitive to the pH of tissue extraction, requiring a pH of 7.0 to 8.4 to be observed. Insulin-mediated inhibition of protein kinase activity was reversed upon preincubation of extracts at 0--2 degrees. Relatively concentrated homogenates (less than 4 microliter buffer/mg tissue) yielded extracts which exhibited little or no inhibition of protein kinase activity compared to extracts prepared from more dilute (6--10 microliter/mg) homogenates. A model for the inhibition of the cyclic-AMP dependent protein kinase by an insulin-generated inhibitor which becomes directly associated with the Type 1 holoenzyme is proposed.
Mol Cell Biochem 1978 Feb 24
PMID:Reversible inhibition of cyclic AMP-dependent protein kinase by insulin. 2 80

Gel filtration of acromegalic or normal serum at acid pH gave two distinct species of non-suppressible insulin-like activity (NSILA), one of high MW and the other of low MW (approximately 7000 daltons). The acid-stable high MW form remained high MW on rechromatography in acid. Gel filtration of serum at neutral pH however, gave only high MW activity, which remained high MW when rechromatographed under neutral conditions but split into both high and low MW forms when rechromatographed in acid. These results indicate that there are at least two circulating forms of NSILA--a low MW form which circulates in serum bound to a carrier protein in an acid-labile high MW complex and a species which circulates only as a stable, discrete high MW protein.
Mol Cell Endocrinol 1979 Nov
PMID:The occurrence of a distinct high molecular weight form of serum non-suppressible insulin-like activity. 4 88

Different B-cell organelles (lamellar and vesicular endoplasmic reticulum, Golgi complex, whole secretory granules and secretory granule cores) were studied stereologically in pancreatic islets from control mice and mice killed 10 or 60 min following alloxan injection. Ten min following alloxan a significant decrease was observed in the volume, surface and numerical densities of whole secretory granules and their cores, and a significant increase was found in the volume and surface densities of vesicular endoplasmic reticulum. At the 60 min observation time, a significant decrease was seen in the volume density of lamellar endoplasmic reticulum and Golgi complex, and in the volume, surface and numerical densities of whole secretory granules and their cores, and a significant increase was observed in the volume and surface densities of vesicular endoplasmic reticulum, and in the mean values for volume and surface of whole secretory granules and their cores. The stereological data indicate swelling of endoplasmic reticulum, decreased Golgi area, and decreased number and total volume and surface of secretory granules during the first hour after alloxan administration to mice. The observations may be consistent with inhibited insulin synthesis.
Virchows Arch B Cell Pathol Incl Mol Pathol 1979
PMID:Stereological study of endoplasmic reticulum, Golgi complex and secretory granules in the B-cells of normal and alloxan-treated mice. 4 17

Drug-induced porphyrin accumulation occurs in chick embryo liver cells maintained in serum-free Waymouth MD 705/1 medium. Addition of insulin and thyroxine to the medium results in a marked enhancement of porphyrin accumulation. The addition of hydrocortisone results in a further enhancement of porphyrine accumulation. Several agents which are reported to increase intracellular adenosine 3':5'-monophosphate (cAMP) levels, viz. glucagon, sodium fluoride, cAMP or its dibutyryl derivative, 3-isobutyl-1-methylxanthine and papaverine enhanced drug-induced porphyrin biosynthesis. On the other have, agents which are reported to decrease intra-cellular cAMP levels, viz. alloxan and imidazole, diminished drug-induced porphyrin accumulation. cAMP appears to enhance, but not to function as a "second messenger" in drug-induced porphyrin biosynthesis. Drug-induced porphyrin accumulation in chick embryo liver cells depend upon the insulin to glucagon ratio. A low level of porphyrin accumulation occurs at insulin to glucagon ratios similar to those found following glucose administration in vivo, suggesting a possible explanation for the therapeutic effect of glucose in hepatic porphyria. The 5 alpha A(A:B trans) and 5 beta H(A:Bcis) steroids are equipotent in inducing delta-aminolevulinic acid synthetase and porphyrin accumulation in chick embryo liver cells maintained in serum-free culture medium. Thus, there is no specific steric requirement for porphyrin-inducing activity in steroids.
Mol Cell Biochem 1979 May 21
PMID:Hormonal effects on the regulation of hepatic heme biosynthesis. 8 65

Thyroid hormones regulate lipid metabolism by affecting lipogenesis as well as lipolysis. The present paper discusses the way thyroidectomy induced an enhancement in lipogenesis in rat fat cells. The doubling in the conversion of glucose to CO2 and fatty acids seen after thyroidectomy was found to be due to a modification in the actual pathway of glucose metabolism: there was a preferential stimulation of the conversion of glucose to CO2 by the pentose cycle (utilisation of [1-14C]glucose) while the production of fatty acids and glyceride-glycerol proceeded, respectively, much more, or only slightly more, via the pathway of [6-14C]glucose metabolism. Studies employing the phosphodiesterase inhibitor MIX, or the cyclic AMP analogue, DBcAMP showed that the lipogenic process depends on cyclic AMP. As the stimulatory effect of thyroidectomy was not abolished, however, lipogenesis must be under the independent control of both cyclic AMP and absence of thyroid hormones. Insulin, a further mediator of lipogenesis was found to further enhance the already preexisting high conversion of glucose to CO2 in fat cells from thyroidectomized rats. It is concluded that at least three factors modify lipogenesis: thyroidectomy, cyclic AMP and insulin; each achieving its effect in an independent manner.
Mol Cell Endocrinol 1979 Jun
PMID:Cyclic AMP and lipogenesis in fat cells from thyroidectomized rats. 8 52

Autoantibodies to the insulin receptor mimic the effects of insulin on glycogen synthase and phosphorylase. The interaction of antibodies with adipocyte cell surface insulin receptors seems sufficient to promote stable changes in the activities of these intracellular enzymes, suggesting that internalization or processing of insulin is not important in the generation of these biological responses.
Mol Cell Biochem 1978 Dec 22
PMID:Autoantibodies to the insulin receptor activate glycogen synthase in rat adipocytes. 10 36

1. Growth hormone secretion was assessed in nine control subjects and nine patients with Huntington's chorea. 2. Early-morning fasting plasma samples from patients with Huntington's chorea contained abnormally high concentrations of growth hormone. 3. The suppression of growth hormone after oral glucose in choreic patients, unlike the control subjects, occurred at irregular intervals after the glucose was given and was followed, again at irregular intervals, by an exaggerated rebound phase. 4. The response to intravenous insulin was not markedly abnormal in choreic patients. However, there was a significant increase in the rate of rise of growth hormone concentration in the first half and hour after the insulin injection when compared with control subjects.
Clin Sci Mol Med 1976 Jun
PMID:Plasma growth hormone concentrations in Huntington's chorea. 13 32

1. Kidney weight and content of protein, RNA and DNA were measured in rats with streptozotocin diabetes of varying duration. 2. Diabetic rats had larger kidneys than control rats: after 3 days of diabetes the weight increase was 15 per cent and after 42 days of diabetes it was 90 per cent. The protein content rose in parallel to the weight. 3 RNA content was already increased after 36 h of glycosuria, whereas DNA content was unchanged for the first 3 days of diabetes, and increased thereafter. The protein/DNA ratio increased rapidly during the first 3 days but remained constant thereafter. 4. Insulin treatment decreased the renal weight gain by about 67 per cent during the first 8 days of diabetes, but did not prevent the increase in DNA. When insulin was started after 25 days of diabetes there was only a slight regression of kidney growth.
Clin Sci Mol Med 1976 Dec
PMID:Renal hypertrophy in streptozotocin-diabetic rats. 13 97

1. The metabolic responses to an oral glucose tolerance test (100 g) and an intravenous insulin provocation test (0-1 i.u./kg) were studied in nine control subjects and nine patients with Huntington's chorea. 2. Plasma glucose responses to these stimuli were identical in both groups. 3. High fasting concentrations of non-esterified fatty acid (NEFA) were recorded in the choreic patients when compared with control subjects. This difference was maintained under hypoglycaemic conditions. However, during hyperglycaemia the differences in NEFA concentrations between the groups was abolished. 4. Total plasma tryptophan concentrations were equal in the two groups. Free plasma tryptophan, however, was markedly reduced in the choreic group, and this appeared to be a result of a disturbed relationship between free tryptophan and NEFA concentrations. The abnormalities in free tryptophan values were sensitive to plasma glucose concentrations, as hyperglycaemic conditions markedly reduced the differences between the choreic and control group. 5. Patients with Huntington's chorea showed reduced fasting plasma concentrations of leucine, isoleucine and valine.
Clin Sci Mol Med 1977 Mar
PMID:Plasma glucose, non-esterified fatty acids and amino acids in Huntington's chorea. 13 25

1. The plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) response to intravenously administered glucagon has been studied in nine hyperthyroid, five hypothyroid and ten euthyroid patients. 2. Concentrations of the nucleotide rose to a peak at 15 min and declined to near basal values by 120 min, the response being greatest in hyperthyroid and least in hypothyroid subjects. The mean peak concentrations were 1028 nmol/1 in the hyperthyroid group, 252 nmol/1 in the hypothyroid group and 534 nmol/1 in the euthyroid group. 3. These results could not be accounted for by differences in serum insulin response. 4. It is suggested that the response of plasma cyclic AMP to glucagon may serve as an index of tissue thyroid status.
Clin Sci Mol Med 1975 Jan
PMID:Plasma adenosine 3':5'-cyclic monophosphate response to glucagon in thyroid disease. 16 65


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