Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating androgens are known to effect a sexual dimorphism of the submandibular gland and kidney of the mouse. Enzyme histocytochemical differences that correlate with these structural changes have been the subject of much study, especially in the kidney. In the present study, emphasis was placed on the hypogonadic effects of diabetes mellitus on the submandibular gland and kidney of C57Bl/KsJ db/db inbred mice with an autosomal recessive disease resembling maturity onset human diabetes mellitus. These glands of adult diabetic mice of both sexes were compared with those of unafflicted heterozygous littermates. The mitochondrial cytochrome oxidase and peroxisomal and cytoplasmic catalase were studied in their submandibular glands and kidneys. The parasympathetic innervation of the submandibular glands was studied by a histochemical method for acetylcholinesterase. The extensive differentiation of striated ducts of the submandibular gland into granular tubules in the postpubertal male mouse was readily evident with the cytochrome oxidase procedure. This differentiation resulted in ductal staining patterns characteristic of the sexes. Alteration of these patterns suggested that demasculinization or feminization was occuring in the male diabetic mice and that masculinization or virilization (defeminization) was occurring in the female diabetics. Similarly, in kidney, study of the parietal epithelium of Bowman's capsule revealed feminization in the male diabetics and masculinization in the female diabetics. With the catalase procedure, a dramatic sexual dimorphism was observed in the kidneys of the heterozygous unafflicted mice. Peroxisomal staining of epithelial cells of the proximal convoluted tubules was much more intense in the outer medulla of the male than of the female. In kidneys of the diabetics, the staining patterns again suggested that feminization of the male and masculinization of the female kidneys had occurred. On the other hand, neither a sexual dichotomy nor effects due to diabetes could be observed in the characteristic catalase staining observed in the luminal epithelial cells of submandibular gland distal ducts. The parasympathetic innervation of the submandibular gland, as revealed by the acetylcholinesterase method, was also markedly sexually dimorphic in the unafflicted mice. This was due to the more extensive innervation of the larger granular ducts characteristic of male than of the smaller striated ducts of the female. As a result of diabetes, the innervation and duct size decreased in the submandibular gland of the male, suggesting feminization, whereas they increased in the female suggesting masculinization. These changes were consistent with those observed in sumandibular gland with the cytochrome oxidase procedure. Attempts were made to interrelate all of the enzyme histochemical changes observed in submandibular gland and kidney with the weights of these glands, sex, gonadal weights, diabetic status and urinary protein excretion...
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PMID:Cytochemical correlates of structural sexual dimorphism in glandular tissues of the mouse. 741 41

We investigated the effect of Probucol in preventing fatty liver in monosodium-L-glutamate (MSG) treated obese mice and control mice fed a high fat diet. MSG mice became significantly obese 9 weeks after birth with higher levels of serum blood glucose, total cholesterol, HDL-cholesterol, GPT, and cholinesterase, and had greater triglyceride contents in their livers relative to control mice. Morphologically, MSG obese mice also had a marked fatty liver. Administration of Probucol mixed with the high fat diet for 2 weeks significantly decreased the serum levels of total cholesterol and HDL-cholesterol, and liver triglyceride contents in both MSG and control mice. Morphologically, the livers were less fatty after Probucol treatment. These results suggest that Probucol prevents the development of fatty liver, and in addition reduces hypercholesterolemia.
Exp Clin Endocrinol Diabetes 1995
PMID:Probucol prevents the progression of fatty liver in MSG obese mice. 755 75

Enhanced cholinergic and dopaminergic controls of anterior pituitary function have been described in insulin-dependent diabetes mellitus (IDDM). In order to verify whether similar neurotransmitter alterations also affect the regulation of posterior pituitary hormone secretion, the arginine-vasopressin (AVP) responses to the dopaminergic agonist apomorphine and in a different occasion to physostigmine, an acetylcholinesterase inhibitor, were evaluated in normal (n = 10) and type I diabetics (n = 16). In addition, a control test with normal saline was performed in all subjects. None of the diabetic patients were affected by neuropathy or other diabetic complications. They were divided into two groups according to the duration of their disease (less than 10 years: group 1, n = 8; more than 10 years: group 2, n = 8). Physostigmine (12.5 micrograms kg-1) was infused intravenously over 10 min; apomorphine (60 micrograms kg-1) was injected subcutaneously. Basal AVP concentrations were similar in all groups and remained constant during the control test. In contrast, both drugs induced significant increments in plasma AVP levels in the normal controls and diabetic subjects. However, physostigmine- and apomorphine-induced AVP increments were twofold higher in diabetics than in control subjects. No significant differences were observed between diabetics of groups 1 and 2. No significant correlations between duration of diabetes and peak AVP responses to physostigmine or apomorphine were found within each group or when all diabetic subjects were considered together. These data indicate enhancement of both dopaminergic and cholinergic stimulatory regulations of AVP secretion in patients with uncomplicated IDDM, regardless of the duration of diabetes.
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PMID:Dopaminergic and cholinergic control of arginine-vasopressin secretion in type I diabetic men. 765 19

CBL/57 strain db/db mice exhibit type II (noninsulin-dependent) diabetes. The affected mice are markedly hyperinsulinemic, hyperglycemic, and hypercholesterolemic, and their serum K+ levels are decreased. The brains of the diabetic mice are significantly smaller than those of their lean, control littermates, but the protein concentration is normal. The low brain weight is accompanied by a loss of major fatty acid components within the whole brain, nerve endings, and mitochondrial membranes. Cholesterol levels are low in whole brain but are not significantly different from normal in the synaptosomal membranes. The phospholipid concentration is significantly decreased in whole brain homogenates, crude synaptosomal membranes, and crude mitochondrial membranes of the diabetic mice. In addition, the specific activities of membrane-bound synaptosomal acetylcholinesterase, Na+,K(+)-ATPase, and Mg(2+)-ATPase are decreased in crude synaptosomal membranes of the diabetic mice. The specific activities of carnitine palmitoyltransferase I and carnitine acetyltransferase are significantly increased in the crude mitochondrial fraction isolated from the brains of the type II diabetic mice, whereas the specific activity of pyruvate dehydrogenase complex is decreased. The specific activities of two other mitochondrial enzymes--monoamine oxidase B and citrate synthase--and a cytosolic enzyme--lactate dehydrogenase--are unaltered. The ability to synthesize cyclic AMP is markedly decreased in the brains of the diabetic mice. The concentrations of carnitine and of the amino acids, glutamate, aspartate, glutamine, and serine are unaltered, whereas glycine levels are significantly elevated in the brains of the db/db mice. The data suggest that in vivo the brains of the diabetic mice exhibit a decreased capacity for glucose oxidation and increased capacity for fatty acid oxidation. This hypothesis is supported by the finding that cerebral mitochondria isolated from the db/db mice oxidize [1-14C]palmitate to 14CO2 at a rate almost twice that of control mitochondria. The present findings emphasize the potentially serious alteration of brain metabolism in uncontrolled type II diabetes.
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PMID:Lipid metabolism and membrane composition are altered in the brains of type II diabetic mice. 772 1

We examined the effects of alloxan-diabetes on the kinetic properties of the soluble and the membrane-bound forms of acetylcholinesterase (AChE) in rat brain. The Km (0.15 mM) and Vmax. (1.5 mmol/min per mg of protein) of the soluble form of the enzyme were unchanged in the diabetic animals. The membrane-bound enzyme in the control group displayed a lower Km (0.09 mM) and a higher Vmax. (7.2 mmol/min per mg of protein) compared with the soluble form of the enzyme; the diabetic state caused a significant increase (40%) in both Km and Vmax. Kis values were about 3-4 times higher for the membrane-bound enzyme in both control and diabetic animals. The results suggest that membrane binding and membrane alterations in diabetes can significantly influence the kinetic properties of AChE.
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PMID:Alloxan-diabetes alters kinetic properties of the membrane-bound form, but not of the soluble form, of acetylcholinesterase in rat brain. 774 92

Serum pseudocholinesterase (PChE) was discovered in 1932. Since this protein mimics many of the catalytic properties of acetylcholinesterase, it has traditionally been referred to as PChE, even though its true biological function is unknown. Serum PChE is synthesized in the liver and secreted into the circulation as a sialated glycoprotein. Although no convincing evidence of biological function exists, a significant number of obese and diabetic patients have elevated levels of PChE. The same phenomenon is found in experimental animal models of obesity, diabetes and hyperlipoproteinemia. Streptozotocin-induced diabetic mice showed increased serum PChE activity concomitant with increased serum triacylglycerol and PChE activity declined with treatment. Iso-OMPA, a nontoxic inhibitor of serum PChE, reduced serum and liver triacylglycerols and serum VLDL in streptozotocin-induced rodent diabetes. These findings suggest that PChE may have a role in VLDL metabolism.
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PMID:Serum pseudocholinesterase and very-low-density lipoprotein metabolism. 793 19

The effect of experimental diabetes induced in rats was examined in brain areas like the septum, medial preoptic area, median eminence-arcuate region, amygdala, thalamus, hippocampus, pons and medulla. In all the areas studied, acute hyperglycemia caused an increase in the activity of acetylcholinesterase, the degradative enzyme of cholinergic system, whereas insulin administration reversed this effect. These findings suggest that the dysfunction of cholinergic system may also be involved in the diabetes associated CNS complications.
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PMID:Effect of alloxan-induced diabetes on acetylcholinesterase activity from discrete areas of rat brain. 816 42

Autonomic neuropathy is a common complication of diabetes mellitus, and both morphological and physiological data suggest that salivary gland function in diabetic rats is affected by neuropathies involving sympathetic and parasympathetic nerves. Therefore, glandular levels of the adrenergic neurotransmitter, norepinephrine (NE) and two cholinergic enzymes, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), were investigated in 6-month streptozotocin-diabetic rats. Significant, but variable, increases in total parotid NE (ng/gland) were observed in diabetic rats, whereas total submandibular NE was lower in diabetic animals than in controls. However, on a ng/mg tissue basis, NE levels in both the parotid gland, and less dramatically, in the submandibular gland were increased. Somewhat different results were observed for AChE and ChAT. AChE was marginally greater in the parotid glands of diabetic rats, whereas AChE and ChAT levels were significantly lower in diabetic than control submandibular glands. Expressed as enzymatic activity per mg tissue, submandibular gland ChAT, but not AChE, was increased. Short-term (3-day) insulin treatment of diabetic animals had no significant effects on total NE, AChE or ChAT in the parotid gland, but led to a further reduction in submandibular ChAT. With regard to function, changes in AChE appeared to be correlated with previously reported morphological assessments of parotid gland innervation in diabetic animals. Thus, the decreased response of the parotid gland in diabetic rats to parasympathetic stimulation may be related in part to the increase in AChE.
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PMID:The effects of streptozotocin-induced diabetes on norepinephrine and cholinergic enzyme activities in rat parotid and submandibular glands. 818 4

In this study we examine the hypothesis that an inositol glycan phosphate can act similarly to insulin on intact cells. The inositol glycan phosphate used in this study (glycan alpha) was isolated previously from the glycoinositol phospholipid anchor of human erythrocyte acetylcholinesterase and was shown to have the structure glycine-ethanolamine-PO4-Man-Man-(N,N-dimethylethanolamine-PO4)Man- (N,N-dimethyl)GlcN-inositol-PO4. The cellular response investigated was the glucagon-stimulated activation of glycogen phosphorylase in rat hepatocytes. When hepatocytes were incubated with 20 nM glucagon for 4 min, the ratio of phosphorylase a activity to total phosphorylase increased from a basal value of 0.49 +/- 0.02 to 0.82 +/- 0.03 (mean +/- SE, n = 15). Inclusion of either 100 nM insulin or 3-10 microM glycan alpha during the glucagon incubation significantly decreased the glucagon-stimulated activity ratio to 0.74 +/- 0.03 for either agent. Furthermore, hepatocyte preparations differed in their response to insulin and were divided into insulin-responsive and -resistant groups. Glycan alpha had a significant effect only in the insulin-responsive group for which the observed activity ratio for 10 microM glycan alpha plus glucagon (0.68 +/- 0.05) compared closely with that for insulin plus glucagon (0.70 +/- 0.04). For the insulin-resistant group, the activity ratio in the presence of 10 microM glycan alpha was 0.81 +/- 0.03, unchanged from the control with glucagon alone. Because glycan alpha contains an inositol phosphate group, the effect of inositol cyclic 1,2-phosphate on the glucagon-stimulated activity ratio was determined.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Sep
PMID:Inositol glycan phosphate derived from human erythrocyte acetylcholinesterase glycolipid anchor and inositol cyclic 1,2-phosphate antagonize glucagon activation of glycogen phosphorylase. 834 43

Accuracy in measurement of plasma free fatty acids (FFA), and therefore prevention of the in vitro lipolysis, is a crucial step to understand the physiologic role of plasma FFA and their relationships in the pathogenesis of important metabolic disorders such as central obesity, insulin resistance, and diabetes mellitus. As lipoprotein triglyceride-fatty acids are elevated in these states, in vitro lipolysis of triglycerides may artifactually increase FFA. Plasma FFA were measured in subjects before and after heparin administration, under different experimental conditions affecting the in vitro activity of lipoprotein lipase (LPL) and hepatic lipase (HL). Paraoxon, a cholinesterase inhibitor neurotoxin known to block plasma lipolytic activity, and preextraction timing and temperature of collection were tested. Paraoxon was required to prevent triglyceride hydrolysis in: a) preheparin plasma allowed to stand at room temperature (21 degrees C) for 2 h, before being frozen at -20 degrees C (FFA = 1817 +/- 291 vs. 698 +/- 66 microEq/l, P < 0.005, mean +/- SEM, without and with paraoxon, respectively); and b) in postheparin plasma immediately stored at -20 degrees C (FFA = 2682 +/- 357 vs. 1299 +/- 150 microEq/l, P < 0.005, without and with paraoxon, respectively). No difference in the FFA level was found in preheparin plasma collected either with or without paraoxon when: a) the samples were placed in ice and immediately assayed; b) the specimens were immediately frozen at -70 degrees C and assayed 60 days later.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of techniques to obtain plasma for measurement of levels of free fatty acids. 835 49


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