Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
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This report describes measurements of 50 variables in adult, female, reproductively inactive Vervet monkeys during prolonged nutrition realistic for westernized people. Dietary treatments consisted of an atherogenic Western diet (WD) and a prudent Western diet (PD). Ingredients were normal foods for man and no extra cholesterol was added. Fortification of both diets with vitamin C after cooking was necessary to prevent deficiency. Randomised groups of Vervet monkeys received either the PD or WD for 47 months, while a third group was fed WD for 20 months and then PD for 27 months (WD-PD). Before the dietary treatments nourishment was by a high carbohydrate diet (HCD) and baseline and reference values (RV) apply to this nutritional status. Plasma total cholesterol (mg/dl) was increased from 147 (HCD) to 174 (PD) and 376 (WD). Individual cholesterolaemio response ranged from mild to severe and was stable (PD and WD). Dietary reversal (WD-PD) reduced cholesterolaemia promptly. Statistically significant increases in calcium, zinc and vitamin E and decreased vitamin B6 were associated with the WD relative to the PD (in serum and plasma). Two cholesterol metabolising microsomal enzymes in liver were notably increased and one unchanged (WD). There were no dietary effects on triglycerides, vitamin A and glucose in plasma; insulin, glucagon, electrolytes, copper, magnesium or enzymes reflecting liver, muscle or brain cell damage in serum. Red blood cells, platelets and directly associated parameters increased (WD), haemoglobin was the same and haemoglobin per red cell decreased. Bleeding time was not affected. Bivariate correlations across the diets confirmed that Western nutrition promoted inherent individual susceptibility to cholesterolaemia. There were notable differences from RVs in total cholesterol, calcium, packed cell volume and haemoglobin, which emphasise excesses and deficiencies of the WD and PD.
Atherosclerosis 1987 Aug
PMID:Diets realistic for westernized people significantly effect lipoproteins, calcium, zinc, vitamins C, E, B6 and haematology in vervet monkeys. 363 58

The diurnal variation of intermediary metabolites and hormones was determined, as 24-h profiles, in a group of subjects with mixed hypertriglyceridemia while consuming a diet with excess alcohol and caloric intake (Hyp-I) or after a hypotriglyceridemic diet (Hyp-II), and in normal controls. Alcohol was excluded from the hypotriglyceridemic diet and on the days of the study. Hyp-I subjects showed higher 24-h levels of plasma triglyceride, glucose, insulin, lactate, pyruvate, free fatty acid and glycerol. After the hypotriglyceridemic diet the levels of pyruvate, free-fatty acids and glycerol in plasma were normalized, while triglyceride, insulin and glucose concentrations were significantly reduced but remained still higher than in controls. The elevated lactate concentration in Hyp-I subjects were unaffected by the diet. In Hyp-I subjects free-fatty acids and glycerol levels were not suppressed following the meal, in contrast to controls. After the diet this defect in the suppression of endogenous lipolysis was only partially reversed in Hyp-II subjects. Plasma alanine, total ketone body and glucagon concentrations were unaffected. In conclusion, in mixed hypertriglyceridemia high lactate concentration and a defect in the suppression of endogenous lipolysis after a meal could represent a factor enhancing triglyceride production.
Atherosclerosis 1986 May
PMID:Hormonal and metabolic profiles in patients with alcohol-induced, mixed hypertriglyceridemia before and after abstinence from ethanol and before and after a lipid-lowering diet. 371 12

The aging kidney suffers reduction both in mass and in glomerular filtration rate. These changes may be totally or partially due to atherosclerosis and hypertension, which reduce renal blood flow. Superimposed on these processes, and perhaps responsible for primary loss of renal mass irrespective of renal vascular disease, is glomerular damage and involution that is a consequence of adaptive increases in glomerular perfusion pressure that occurs as the number of nephrons decline with age. The data available at this time do not allow us to distinguish between these two potential mechanisms of renal senescence. The decline in GFR is in turn responsible for reduced renal acidification and the reduced renal clearance of drugs that are normally removed by the kidney. Certain renal functions, however, are depressed to a greater extent than is GFR. Both the ability to maximally dilute the urine and to maximally concentrate it are controlled by serum ADH concentrations and by the action of that hormone on the collecting duct. Aged rats do not maximally secrete ADH under conditions of dehydration and the effect of ADH on the kidney is also attenuated. Elderly humans also cannot maximally suppress ADH secretion when serum osmolality is reduced. Likewise, the renin-angiotensin-aldosterone axis is poorly responsive to volume depletion in aging subjects. As a result, elderly individuals cannot maximally retain sodium under conditions of plasma volume contraction out of proportion to reduction in GFR. The kidney is the site of vitamin D1 hydroxylation. Hydroxylation of vitamin D is reduced out of proportion to any reduction in GFR in the rat. There are no data as yet available on the effect of aging and the production of erythropoietin, a principal regulator of red blood cell mass. Neither are there data available on changes that might occur with advancing age in the ability of the aging kidney to metabolize various hormones, such as parathyroid hormone, glucagon, and insulin. The mechanisms and the full biochemical and physiologic consequences of renal senescence remain to be fully elucidated.
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PMID:The aging kidney. 391

Post-heparin lipase activities were measured in normolipemic men with complaints suggestive of symptomatic coronary artery disease. A study group, who showed diffuse atherosclerotic narrowing of the coronary vessels, assessed by a quantitative computer-assisted analysis method, had a lowered hepatic lipase in comparison with a group with normal angiograms. Lipoprotein lipase was lower in the study group but well within the normal range and not statistically different. Some related hormones (cortisol, estradiol, testosterone and glucagon) were different in the two groups while others (insulin, human growth hormone, prolactin, thyroid hormones) were not. The results are discussed in view of the proposed role of hepatic lipase in the uptake of HDL-cholesterol by the liver.
Atherosclerosis 1983 Sep
PMID:Post-heparin lipases, lipids and related hormones in men undergoing coronary arteriography to assess atherosclerosis. 635 16

In 120 consecutive patients undergoing diagnostic coronary arteriography, fasting blood glucose, plasma insulin, glucagon, serum cholesterol and triglyceride concentrations were measured. The insulin-glucose ratio and insulin-glucagon ratio were calculated. Forty-five patients had normal coronary arteries, 19 had single vessel coronary artery disease and 56 patients had multiple vessel disease. Fasting blood glucose was greater than 120 mg/100 ml in 37 patients (group A) and included 9 of the 10 known diabetics, 3 of whom were being treated with insulin. Seventy-seven patients included in group B had fasting blood glucose concentration less than 120 mg/100 ml. Patients with multiple vessel coronary disease in either group had higher blood glucose and cholesterol concentrations than those with normal coronary arteries or the ones with single vessel disease, but they did not have higher plasma insulin or glucagon levels nor increased insulin-glucose or insulin-glucagon ratios. With comparable extent of coronary artery disease patients in group A had higher plasma insulin levels and insulin-glucagon ratios than those in group B, but no correlation exists between the presence or extent of coronary atherosclerosis and these variables in either group. Thus, neither fasting plasma insulin level nor insulin-glucagon ratio predicts the status of underlying coronary atherosclerosis in either diabetics or nondiabetics.
Atherosclerosis 1984 Oct
PMID:Lack of relationship between plasma insulin and glucagon levels and angiographically-documented coronary atherosclerosis. 638 87

Fractions of fenugreek seed were added to the diet of normal or diabetic hypercholesterolaemic dogs for 8 days. The effects on levels of blood glucose, plasma glucagon and plasma cholesterol were investigated. The lipid extract had no effect. The defatted fraction which is rich in fibres (53.9%) and contains 4.8% of steroid saponins significantly lowered basal blood glucose (P less than 0.02), plasma glucagon (P less than 0.01) and plasma cholesterol (P less than 0.02) levels in normal dogs. The addition of this fraction to the food of diabetic hypercholesterolaemic dogs caused a decrease of cholesterolaemia (P less than 0.02) and reduced hyperglycaemia. In conclusion, the defatted portion of fenugreek seed induces a hypocholesterolaemic effect.
Atherosclerosis 1984 Jan
PMID:Hypocholesterolaemic effect of fenugreek seeds in dogs. 669 79

Portacaval anastomosis (PCA) lowered by 50% the cholesterol concentration in the plasma of rats. The free and esterified cholesterol contents in the lipoproteins were decreased with the very low density lipoproteins most affected (-85%). Cholesterol concentration as total content in the liver was reduced. The major change in the cholesterol metabolism, as studied with an isotopic equilibrium method, was the decrease in the intestinal absorption coefficient of dietary cholesterol (56.0 +/- 2.7% instead of 73.3 +/- 1.9% in controls). The rate of cholesterol transformation into bile acids was decreased (10.5 +/- 0.3 vs 14.5 +/- 0.5 mg/day/rat in controls). The rate of internal secretion of cholesterol was slightly reduced while the rate of fecal external secretion was increased, suggesting that the synthesis of cholesterol by extra-digestive tissues (including liver) was reduced after PCA. The effects of PCA on cholesterol metabolism were similar to those described for glucagon administration. Since this shunt results in hyperglucagonemia, it is suggested that this hormonal perturbation was the main factor involved in the modifications of cholesterol metabolism after PCA. Moreover, mesentericocaval anastomosis, which shunts only the intestinal blood and allows the pancreatic hormones a normal transport through the liver, did not significantly modify cholesterol metabolism. Only cholesterolemia (-28%) and the absorption coefficient of dietary cholesterol (66.0 +/- 2.3%) were slightly reduced.
Atherosclerosis 1983 Jan
PMID:Effect of portacaval or mesentericocaval anastomosis on cholesterol metabolism in rats. 683 96

Nine prepubertal obese boys ages 9 1/2 to 12 yr followed moderately restricted diets and moderate exercise routine for 31 wk. Foods were selected from the family's basic diet and the physical activities were tailored to the home environment. This dietary (approximate decrease of 600 kcal/day) and activity (approximate increase of 300 kcal/day) intervention program was sufficient to stop weight gain and normalize key metabolic indices for prediction of atherosclerosis, hypertension, and diabetes. Throughout the treatment period serum lipid responses included significantly lower (p less than 0.05) total cholesterol, low-density lipoprotein-cholesterol and triglycerides. High-density lipoprotein-cholesterol was constant throughout the period. Responses in carbohydrate metabolism included significantly lower (p less than 0.05) fasting insulin and glucose. Insulin and glucose levels were positively correlated with total caloric consumption and insulin was also positively correlated with sucrose consumption (p less than 0.05). Fasting insulin/glucose ratios and glycosylated Hb decreased throughout the treatment period, but serum glucagon levels remained constant. In response to a glucose load, insulin and glucose decreased significantly by wk 31 of treatment. A practical approach for normalizing metabolism in obese male children is presented.
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PMID:Moderate diet control in children: the effects on metabolic indicators that predict obesity-related degenerative diseases. 704 93

Regulation of the key enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl CoA reductase (EC: 1.1.1.34), by heterologous human lipoproteins and hormones was studied in a maintenance culture of rat hepatocytes. The liver cells were cultured under hormone and serum free conditions and maintained differentiated morphology and specific function. Under control conditions total HMG-CoA reductase increased by 50% after 24 h culture compared to 0 h values immediately after isolation. Thereafter a plateau of enzyme activity was reached lasting until 48 h, with a slight decline at 72 h. Concomitantly the "expressed" enzyme activity increased steadily, probably through dephosphorylation of latent reductase, the activation was largely complete at 48 h. During the steady state period of total reductase VLDL added to the medium at concentrations up to 50 microgram/ml protein had no effect o HMG-CoA reductase activity. In contrast, LDL suppressed the enzyme in a dose-dependent fashion to 40% of controls at 100 microgram/ml. On the other hand, HDL had the opposite effect with a significant induction up to 252% of controls at 50 microgram/ml. Insulin also caused a comparable dose-dependent stimulation of enzyme activity at 10(-8) and 10(-7)M, whereas glucagon inhibited reductase activity. Compared to the insulin action, triiodothyronine and triamcinolone prompted a minor, but still significant increase of reductase activity. Insulin and triamcinolone acted synergistically, but the combination of triamcinolone and tri-iodothyronine was only additive. All hormonal inductions of reductase could be blocked by cycloheximide. The present data establish that HMG-CoA reductase of maintenance cultured hepatocytes is subject to a complex regulation by heterologous lipoproteins as well as pancreatic, adrenal and thyroid hormones.
Atherosclerosis 1982 Jan
PMID:3-Hydroxy-3-methylglutaryl CoA reductase in cultured hepatocytes. Regulation by heterologous lipoproteins and hormones. 707 95

Microvascular complications of diabetes can be forestalled by effective glycemic control. However, the inherent limitations of standard subcutaneous insulins reduce their ability to control glycemia without risk of significant hypoglycemia and hyperinsulinemia. Hypoglycemia is unacceptable for most patients and may be dangerous. Hyperinsulinemia is undesirable because it causes weight gain and it has a putative association with atherosclerosis. This paper summarizes the major historical improvements in insulin therapy, and calls attention to the fact that none of the presently available commercial preparations in any combination is capable of simulating the profile of normal insulin secretion--the latter being regarded as the most effective means of normalizing glycemia. For this reason, a variety of new approaches to simulating the pharmacokinetics or glucodynamics of insulin secretion are under investigation. Fast-acting insulin analogues suitable for subcutaneous injection have been developed and appear to mimic the physiological insulin response more closely than standard insulins. Less progress has been made with basal insulins. Intravenous insulin has pharmacodynamic advantages but practical disadvantages of administration. Nasal insulin would be an attractive treatment modality only if its bioavailability could be significantly increased and its safety assured. Other interventions which improve glucose metabolism without necessarily simulating normal insulin secretion are under investigation. These include biosynthetic human C-peptide, insulin-like growth factor-1 and glucagon-like peptide 1 (7-36 amide).
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PMID:Improving insulin therapy: achievements and challenges. 770 65


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