Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin release in response to glucose was measured after culture of islets from ob/obmice in a medium deficient in Ca2+. When present at a concentration of 6 mmol/l, glucose inhibited, insulin release. After activation of the alpha2-adrenergic receptors by 1 mumol/l clonidine also 20 mmol/l glucose became inhibitory. The inhibitory action of glucose on insulin release disappeared in the presence of 1 mmol/l dibutyryl cyclic AMP. Raising the glucose concentration from 3 to 20 mmol/l resulted in increased cytoplasmic Ca2+ after an initial depression. Whereas clonidine removed the Ca2+ increase, this phase was partly restored after simultaneous addition of dibutyryl cyclic AMP. It is concluded that cyclic AMP plays a major role in controlling the balance between the stimulatory and inhibitory components in the glucose action on insulin release.
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PMID:Reversal of glucose-induced inhibition of insulin release by dibutyryl cyclic AMP. 255 Feb 72

One of the leading causes of mortality in diabetics is myocardial disease. In the past few years this subject has generated a significant amount of interest with the result that myocardial problems associated with diabetes are far better understood. Though originally thought to occur as a result of atherosclerosis, various studies have shown that heart disease can occur in the absence of atherosclerosis, suggesting a diabetic cardiomyopathy. Using diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Diabetic rat hearts do not respond to conditions of high stress as well as controls. The functional depression is accompanied by altered cardiac enzyme systems. A decrease in myosin ATPase activity which appears to be a result of diabetes-induced hypothyroidism is seen. Also, a depression of sarcoplasmic reticular calcium ATPase, along with a depression of calcium uptake by the SR, is seen in diabetic rat hearts. Na+, K+ ATPase activity has also been shown to be depressed and the depression appears to correlate with depressed atrial contractility. High levels of circulating fats in diabetics may alter the integrity of membranes leading to altered enzyme activities. Insulin treatment has been relatively successful at reversing or preventing myocardial changes in the diabetic rat. Other treatments that have been studied include thyroid hormone treatment, since the depression of myosin ATPase can be corrected by such treatment; and carnitine treatment, as the elevation of long chain acyl carnitines (LCAC) and the resulting depression of calcium uptake in the SR can be so normalized. These treatments have not been successful at normalizing cardiac function. A combination of the two treatments normalized function only partially, suggesting that factors besides myosin ATPase and SR calcium uptake are involved. Other treatments that have been tried include vanadate, methyl palmoxirate, and choline and methionine. Vanadate treatment has proved to be encouraging in that it normalizes both function and hyperglycemia. Methyl palmoxirate, a fatty acid analog, normalized only the elevation of LCAC but did not affect function. Methionine and choline were only partially successful in preventing the functional alterations of diabetic rat hearts. The purpose of the present article is to review our understanding of diabetes-induced myocardial problems and their possible causes. Findings from our laboratory and others are described in which attempts have been made to normalize cardiac function.
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PMID:Diabetes-induced abnormalities in the myocardium. 293 41

Reversal of myocardial biochemical changes with insulin treatment (4 and 8 wk) was studied in 8 and 12 wk streptozotocin (STZ)-diabetic rats. STZ-induced diabetes was characterized by elevations in blood glucose, serum cholesterol, and triglycerides and depressed serum insulin levels. Insulin treatment for 4 and 8 wk completely restored the serum alterations to control values. The polyuria, polydipsia, and polyphagia were also markedly diminished by the insulin treatment. Diabetic rats had pronounced decreases in body, heart, and left ventricular weights, all of which were completely reversed by the insulin treatment. Hydroxyproline accumulation in diabetic rat hearts was only reversed by the 8-wk and not by the 4-wk insulin treatment. STZ produced a significant depletion of left ventricular magnesium content as well as depression of K+-stimulated sarcoplasmic reticulum and myofibrillar ATPase activities. Both the 4- and 8-wk insulin treatment produced a complete recovery of the myocardial magnesium content. No significant changes in sarcolemmal Na+-K+-ATPase and K+-stimulated p-nitrophenyl phosphatase activities were observed in diabetic animals compared with control. The decreased latency of the lysosomal hydrolase, N-acetyl-beta-glucosaminidase, and the increased collagen deposition observed in the diabetic hearts were only partially reversed by the 4-wk insulin treatment, but completely reversed by the 8-wk treatment period.
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PMID:Insulin reversal of biochemical changes in hearts from diabetic rats. 294 95

Although clinically undistinguishable, some authors have found important differences in the counterregulatory response between Biosynthetic Human Insulin (BHI) and Purified Pork Insulin (PPI). To reassess the problem 10 healthy volunteers of both sexes underwent paired iv insulin tolerance test with both BHI and PPI (0.10 U/kg b.w.). To check the humoral response the variations of glucose, free fatty acids (FFA), prolactin, growth hormone, ACTH and plasma renin activity were evaluated. Blood glucose depression and further recovery by BHI and PPI administration paralleled each other, so were, prolactin, FFA, and plasma renin activity. A slight section of ACTH, and GH was observed under BHI challenge. There were not statistically significant differences between both insulins on any of the six parameters studied. The data do not confirm earlier published reports indicating hormonal and metabolic differences between human and porcine insulin.
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PMID:Metabolic and hormonal parameters after insulin-induced hypoglycemia in man, comparison between biosynthetic human insulin and purified pork insulin. 299 43

The purpose of this study was to determine whether the energy metabolism of an experimental rodent sarcoma was selectively depressed by the combination of inhibition of glycolysis and respiration. In vivo phosphorus-31 nuclear magnetic resonance spectroscopy was used to monitor the response of tumor or brain high-energy phosphate compounds to insulin hypoglycemia, rhodamine 123, or both agents in fasting rats with subcutaneous methylcholanthrene-induced sarcomas. Insulin or rhodamine 123 alone produced a similar 50% to 60% reduction in tumor adenosine triphosphate (ATP) concentration compared with controls injected with saline solution (p less than 0.05, one-way analysis of variance [ANOVA]). The combination of insulin plus rhodamine 123 resulted in a 90% reduction of tumor ATP concentration, which was significantly different from the effect of either agent alone (p less than 0.05, one-way ANOVA). Brain phosphocreatine and ATP concentrations were unchanged by these agents. Administration of dimethyl sulfoxide (DMSO)/glycerol, the vehicle for rhodamine, produced a 35% reduction of tumor ATP, which was similar to the effect of insulin alone but significantly different from rhodamine. The combination of DMSO/glycerol plus insulin hypoglycemia resulted in a 70% reduction in tumor ATP, which was significantly elevated compared with the combination of rhodamine plus insulin. Glucose deprivation induced by insulin, and combined with the inhibition of oxidative phosphorylation, produces an additive depression of tumor energetics. The drug vehicle DMSO/glycerol significantly depresses tumor energy metabolism, presumably because of its DMSO component, which may explain the previously reported antineoplastic efficacy of this solvent. Combinations of inhibitors directed at different points of tumor metabolism produced an enhanced depression of tumor energetics, whereas host tissue was protected.
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PMID:Inhibition of tumor high-energy phosphate metabolism by insulin combined with rhodamine 123. 304 41

In the first part, we study the interaction of the insulin receptor with model membranes of dimyristoylphosphatidylcholine (DMPC) by various techniques, including calorimetry, densitometry, static light scattering, and electron microscopy. By analyzing the pronounced depression of the lipid chain melting transition in terms of the Van Laar-Hildebrand theory of regular dilute solutions, an (exothermic) interaction energy of Wp = 2000 kJ.mol-1 is found for the receptor and of WL = 0.6 kJ.mol-1 for the lipid. This is interpreted in terms of an adsorption of the 2 hydrophilic head groups of the receptor to the membrane surface so that 1 protein interacts with about 2000 lipids. This number is verified by freeze-fracture electron microscopy. Binding of insulin induces a remarkable decoupling of the receptor head group from the membrane, pointing to a pronounced conformational change. In the second part, we introduce a simple fluorescence technique by which adsorption isotherms of water-soluble and fluorescent-labeled substrates, such as insulin, to membranes may be determined. It is based on the selective evanescent field excitation of ligands adsorbed to supported planar bilayers on argon-sputtered glass plates. These are deposited by the monolayer transfer technique or by vesicle condensation. The reconstituted receptor exhibits a weak (binding constant Kw = 3 X 10(9) L.M-1) and a strong (binding constant Ks greater than 10(10) L.M-1) binding site. Insulin exhibits a weak but remarkable nonspecific binding to bilayers of pure DMPC and DMPC containing 20% positively charged lipid and a strong binding to DMPC containing negatively charged lipids such as phosphatidylserine or ganglioside (GT1b).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction of insulin receptors with lipid bilayers and specific and nonspecific binding of insulin to supported membranes. 306 58

The effects of alloxan-induced diabetes on uterine decidualization and the associated changes in uterine blood flow (UBF) and corpus luteum activity were evaluated in rats between days 4-9 of pseudopregnancy (day 0 = ovulation). Rats were made diabetic (D) with a 40 mg/kg injection (iv) of alloxan on day 1 of pseudopregnancy. Saline-treated rats served as controls (C). Uterine weights were depressed in D rats between days 6-7 of pseudopregnancy in association with elevated blood glucose levels (greater than 300 mg/dl) relative to control values. UBF rates were also depressed in D rats between days 6-7 of pseudopregnancy compared with control values. Insulin replacement therapy (6 IU bovine/day) effectively normalized both uterine weight and UBF in diabetic rats. Decidual tissue (DT) growth was impaired in D rats between days 7 and 9 of pseudopregnancy (DT induction on day 4 of pseudopregnancy) compared with controls. Tissue blood flow rates were severely depressed throughout pseudopregnancy in D rats, but insulin treatment normalized both uterine parameters to control levels. Serum progesterone levels were lower in D rats than in controls between days 7 and 9 of pseudopregnancy. Daily insulin treatment normalized luteal function to control levels. The depressed DT weights in D rats were mimicked by the experimental reduction of DT blood flow in control rats. These results indicate that the uterine atrophy and poor endometrial decidualization that characterized the D rat are accompanied by impaired UBF and luteal activity. These findings suggest that the D-associated depression in female reproductive performance is related to the lack of proper hormone support of tissue vascular dynamics.
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PMID:Effects of diabetes on uterine condition, decidualization, vascularization, and corpus luteum function in the pseudopregnant rat. 327

Effects of epinephrine (Epi) infusion on the absorption of subcutaneously injected 125I-labeled soluble human insulin (10 U) from the thigh or the abdomen were studied in 16 healthy subjects and from the thigh in 10 insulin-dependent diabetic (IDDM) patients. Epi was infused at 0.3 (high dose) or 0.1 (low dose; healthy subjects) nmol.kg-1.min-1 i.v., resulting in arterial plasma Epi levels of approximately 6 and 2 nM, respectively. Saline was infused on a control day. Insulin absorption was measured as disappearance of radioactivity from the injection site and as appearance of plasma immunoreactive insulin (IRI). Adipose tissue blood flow was measured with the 133Xe clearance technique. First-order disappearance rate constants of 125I from the thigh depot decreased approximately 40-50% during the high dose of Epi compared with control (P less than .001). The corresponding decrease from the abdominal depot was approximately 40% (P less than .001), whereas no significant change was found during the low Epi dose. IRI fell compared with control in all groups at the high Epi dose. The Epi-induced depression of insulin absorption occurred despite unaltered or even slightly increased subcutaneous blood flow. The results indicate that circulating Epi at levels seen during moderate physical stress depresses the absorption of soluble insulin from subcutaneous injection sites to an extent that might be important for glycemic control in IDDM patients. Furthermore, dissociation is found between changes in insulin absorption and subcutaneous blood flow during Epi infusion, suggesting that factors other than blood flow may also influence the absorption of subcutaneously injected insulin.
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PMID:Influence of circulating epinephrine on absorption of subcutaneously injected insulin. 328 90

Rat liver sterol carrier protein (SCP) is a major intracellular protein regulating lipid metabolism and transport. During a dark-light cycle, SCP undergoes a dramatic diurnal variation in synthesis and level, reflecting translational events. Several hormones participate in the control of SCP synthesis. Insulin was implicated when the circadian rhythm of SCP was lost in both diabetes and fasting, states where insulin is low. After a 12-h fast the amplitude of the diurnal rhythm is diminished; after a 48-h fast it disappears, although SCP synthesis and level remain high. When endogenous insulin secretion is increased in fasted rats by glucose administration, SCP increases 2-fold in less than 30 min. When food intake is manipulated, but the dark-light cycle is unchanged, the circadian rhythm of SCP corresponds to feeding patterns and not light cycling. During feeding, increases in SCP are triggered following the expected increase in serum insulin. However, SCP is rapidly and significantly elevated in response to insulin only when glucocorticoids are normally high or increased by injection of the synthetic glucocorticoid, dexamethasone. Hepatocyte SCP levels are also induced by a combination of insulin and dexamethasone (2.3-fold) or insulin alone (1.3-fold). Dexamethasone alone causes a striking depression of SCP (2.4-fold). Thus, insulin is a major regulator of the diurnal variation of SCP synthesis. Glucocorticoids and other hormones (e.g. triiodothyronine) are also essential for maximum induction of SCP but play permissive roles.
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PMID:Hormonal triggering of the diurnal variation of sterol carrier protein. 351 Oct 56

Eight patients are reported who attempted suicide by self-administering insulin. Review of the literature reveals that most patients who attempt suicide in this manner are insulin-requiring diabetics, and depression or another psychiatric illness is recognized in the majority. The amount of insulin used varied from 20 units to 3200 units. The duration of the hypoglycemic effect that may be as long as several days, seems to correlate with the dose and type of insulin administered, and may be determined predominantly by the slow release of insulin from the injection site. Recurrence of insulin overdose has been frequently documented. The adult respiratory distress syndrome, not previously described in patients with insulin overdose, occurred in two of our cases, and various mechanisms for this complication are considered. Serious neurologic sequelae and death may be related to delay in therapy, and glucose requirements appear to be higher during the first 24 hours of therapy. Insulin overdose with suicidal intent may be more common than generally thought and should be considered in diabetic patients with severe unexplained hypoglycemia.
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PMID:Insulin overdose in eight patients: insulin pharmacokinetics and review of the literature. 389 66


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