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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Salivary gland striated duct cells play an important role in the modification of primary saliva by secretion and reabsorption of electrolytes, and secretion of glycoproteins. Recent observations have shown that in the rat parotid gland these cells are able to internalize exogenous proteins, e.g., horseradish peroxidase and ferritin, from the ductal lumen. In rats made diabetic by injection of streptozotocin, dense vacuoles and crystalloids are present in the apical cytoplasm of parotid striated duct cells. In this study we utilized electron microscopic immunocytochemistry to determine if these vacuoles and crystalloids contain acinar secretory proteins. At various times after induction of diabetes by streptozotocin (65 mg/kg), the parotid glands were fixed in a glutaraldehyde-formaldehyde mixture, postfixed in OsO4, and embedded in epoxy resin. Thin sections were immunolabeled with antibodies to protein B1 (Ball et al., 1988) and alpha-amylase (Baum et al., 1982) using a modification of the Protein A-gold technique (Bendayan and Duhr, 1986). With antibody to B1, label was localized in the secretory granules of acinar and intercalated duct cells of both normal and diabetic rats. In striated duct cells of diabetic rats, label was present over the electron-dense vacuoles but not over the crystalloids. Since crystalloids appear to form within the vacuoles, their lack of reactivity may indicate degradation of the internalized protein. The same distribution of label was found with antibody to amylase except for the intercalated duct granules, which were unlabeled in both control and diabetic animals. These results demonstrate that striated duct cells take up salivary proteins from the lumen and that the endocytosis of some secretory proteins from the saliva may be a significant function of these cells in certain pathological conditions.
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PMID:Endocytosis of parotid salivary proteins by striated duct cells in streptozotocin-diabetic rats. 297 65

Purified osteocalcin from cow and calf bone was analyzed for nonenzymatic glycosylation (glycation) by sodium [3H]borohydride reduction. Calf bone was found to be approximately 5% glycated, while bone from mature cows was 10% glycated. These results were confirmed by a second method which utilizes periodate oxidation followed by formaldehyde fluorescence. Osteocalcin in human bone was also found to be glycated. The content of glycated osteocalcin from the bones of 47 nondiabetic individuals, aged 0.6-97, was dependent upon age. The extent of glycation was lowest in children, was constant through the adult years, and increased linearly in bone taken from individuals aged 60-97. Glycated osteocalcin was purified by boronate affinity chromatography and subjected to one-step Edman degradation. It was established that the site of glycation was the amino-terminal tyrosine. Increases in the amount of glycated osteocalcin in the bones of older individuals may play a role in the pathogenesis of senile osteoporosis and in the osteopenia which may accompany diabetes mellitus.
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PMID:"Glycated" osteocalcin in human and bovine bone. The effect of age. 349 Apr 75

The regular occurrence of autonomic neuropathy, colonic dilatation, and loss of fecal consistency was investigated in streptozotocin-diabetic, age-matched control, and pancreatic-islet--transplanted rats using ultrastructural, histochemical, and biochemical methods. Degenerating unmyelinated axons were observed by electron microscopy in the colonic submucosa and muscularis, ileal mesentery, and splenic pedicle in 5--7 months diabetic animals; similar changes were not found in control rats or animals subjected to islet transplantation three weeks after induction of diabetes and sacrificed 4--6 months later (colon only). Regenerative changes, including axons with identifiable growth cones, were demonstrated in the mesenteric nerves of chronically diabetic animals. Formaldehyde-induced catecholamine fluorescence and cholinesterase histochemistry suggested deficiencies in colonic adrenergic and cholinergic innervation; histochemical findings in islet-transplanted animals were comparable to those of untreated control animals. Biochemical measurements of the adrenergic and cholinergic nervous system marker enzymes dopamine-beta-hydroxylase and choline acetyltransferase, respectively, in colon and spleen confirm a deficit in adrenergic (colon and spleen) and cholinergic (colon) innervation in chronically diabetic animals.
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PMID:Experimental diabetic autonomic neuropathy. 645 33

Seventeen placentas from insulin-dependent diabetic women and ten placentas from non-diabetics were studied with angiography. The fresh placentas were injected in both umbilical arteries with barium sulphate suspension. After fixation in formaldehyde, the placentas were X-rayed, intact and after being sliced in 0.8 cm slices. There were two clearly distinguishable types of intracotyledonary arteries. Type A is long, narrow and usually runs in the periphery of the cotyledon; type B is wider and usually runs towards the centre of a cotyledon. The cotyledons were classified according to the distribution of these two types of arteries. Type I contained only A-arteries and Type II, both A- and B-arteries or only B-arteries. Twelve per cent of the cotyledons in the control group belonged to Type I, but in the diabetes group 29 per cent. One block of tissue from every placenta was examined histologically to check that the contrast medium filled the stem villus vessels but not the capillaries in the peripheral villi. The histological sections in both groups were compared. Endarteritis appeared to be a feature of the diabetes placenta. The angiographic findings were compared with results of previous direct light microscopical studies. A high percentage of hypovascular villi was found in placentas with a high number of Type I cotyledons.
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PMID:The fetal arterial vasculature in placentas of insulin-dependent diabetic mothers. 712 1

A patient with severe idiopathic diabetes insipidus, complicated by diabetes mellitus, was first treated with a combination o clofibrate and chlorpropamide. Urine volume dropped from 18 litres/day (CH2O = 10.5 ml/min) to 3.1-5.1 litres/day (CH2O = -0.1 -+1.1 ml/min) under treatment. Ten months after the beginning of therapy treatment was maintained with chlorpropamide alone; no significant rise in urine volume was observed. After 18 months when therapy was stopped for 5 days urine volume rose to 11.7 litres/day maximum (CH2O = 6.6 ml/min). No obvious side effects occurred under treatment during a follow up for over 18 months. Serum levels for arginine vasopressin before and under treatment were below 1.0 pg/ml. Determination of free water clearance (CH2O) proved to be a highly sensitive and simple method for follow up controls. It is discussed whether the coincidental manifestation of diabetes insipidus and diabetes mellitus may be caused by a single molecular lesion. This hypothesis is supported by data which imply that in both disease chlorpropamide acts via a common molecular mechanism, the blocking of endogenous prostaglandin E2 biosynthesis. Finally a treatment with oral "non-hormonal" drugs like clofibrate and chlorpropamide should be taken into consideration in some cases of diabetes insipidus as is demonstrated by this case report.
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PMID:Treatment of diabetes insipidus complicated by diabetes mellitus with chlorpropamide and clofibrate. 745 91

Transcellular shifts of water and changes in the physiology of water excretion are common in diabetes mellitus and its treatment. Recent evidence indicates that hyperglycemia in diabetic patients, but not in normal subjects, is characterized by elevations of circulating levels of arginine vasopressin (AVP; antidiuretic hormone, ADH). The role and importance of these observations remain to be defined since elevations of plasma AVP levels do not decrease water excretion in diabetic patients. Certain oral sulfonylureas, notably chlorpropamide and tolbutamide, are known to decrease renal free water clearance (CH2O), whereas insulin increases CH2O; the insulin and tolbutamide effects may be clinically trivial, whereas that of chlorpropamide is important. The hyponatremic effect of chlorpropamide may be exaggerated in diabetic patients by concomitant diuretic therapy. Euglycemia during chlorpropamide therapy appears to allow full expression of the action of chlorpropamide on CH2O; hyperglycemia with attendant osmotic diuresis protects chlorpropamide-treated patients against hyponatremia. Inhibition of prostaglandin synthesis with nonsteroidal anti-inflammatory agents enhances expression of the ADH effect on the kidney, but it does not appear to potentiate chlorpropamide hyponatremia. Two other oral sulfonylurea agents, tolazamide and glyburide, increase CH2O. Diazoxide is an antihypertensive thiazide which is antidiuretic as well as hyperglycemic. Thus, abnormalities of water metabolism are common in diabetes mellitus. Whether certain of these abnormalities are clinically important depends upon the presence of the osmotic diuresis of hyperglycemia and the pharmacology of diabetic management.
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PMID:Water metabolism in diabetes mellitus. 745 88

Straight and branched chain aliphatic monoamines, which are not normal tissue constituents, are deaminated selectively by type B monoamine oxidase (MAO-B). They exhibit a high affinity towards the active site of MAO-B and this made them very useful pharmacologically. An anticonvulsant prodrug, Milacemide [2-(N-pentyl)glycinamide] is deaminated by MAO-B and this facilitates a mechanism of delivering glycine into the CNS. We have found that 2-propyl-pentylamine (2-propyl-1-aminopentane) and N-(2-propylpentyl)glycinamide are also converted by MAO-B to valproic acid and glycine both in vitro and in vivo; these compounds, however, cause severe tremor. By attaching a propargylamine group the resultant series of aliphatic propargylamine derivatives have been shown to be very potent selective MAO-B inhibitors. They are chemically quite different from most other MAO-B inhibitors, since they do not possess any aromatic structures. The relatively short chain aliphatic propargylamines, i.e. N-2-pentyl-N-methylpropargylamine and N-2-hexyl-N-methylpropargylamine, are 4 to 5 times more potent and more selective than selegiline (1-deprenyl) with respect to the inhibition of MAO-B in brain following oral administration. Semicarbazide-sensitive amine oxidase (SSAO) catalyzes the deamination of not only longer chain aliphatic amines but also short chain aliphatic amines including methylamine. Formaldehyde is produced from methylamine by SSAO. Increased methylamine deamination may cause cellular damage in some pathological conditions, such as uraemia and diabetes. We have observed that cultured human endothelial cells are damaged by methylamine in the presence of SSAO. Inhibition of the SSAO activity completely protects these cells from the methylamine-SSAO induced damage.
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PMID:Deamination of aliphatic amines by type B monoamine oxidase and semicarbazide-sensitive amine oxidase; pharmacological implications. 793 Dec 56

Methylamine was observed to be deaminated by several semicarbazide-sensitive amine oxidases, which were prepared from blood and vascular tissues of various species, including humans. Although methylamine itself is relatively nontoxic toward endothelial cells obtained from both human umbilical vein and calf pulmonary artery, it becomes very toxic in the presence of SSAO. SSAO inhibitors (i.e., MDL-72974A) effectively protected the cells from methylamine-SSAO-induced damage. The cytotoxicity seems, therefore, to be a consequence of the deamination of methylamine. Our findings suggest that formaldehyde, the deaminated product of methylamine, may be responsible for these toxic effects. Human serum, which also contains SSAO, was also capable of deaminating methylamine and causing cytotoxicity to cultured endothelial cells. Both methylamine and SSAO circulate in human blood, and their concentrations in the blood of normal healthy subjects are quite close to those required to induce cytotoxicity in tissue-cultured cells. Both SSAO activity and methylamine levels have been reported to be increased in the blood of diabetic individuals. Blood SSAO activity also has been reported to be elevated in the blood of STZ-induced diabetic rats. It is possible, therefore, that an abnormal metabolism of methylamine may be involved in endothelial injury, and that it may subsequently induce atherosclerotic plaque formation and thus be involved in the cardiovascular disorders seen in diabetes.
Diabetes 1993 Apr
PMID:Oxidative deamination of methylamine by semicarbazide-sensitive amine oxidase leads to cytotoxic damage in endothelial cells. Possible consequences for diabetes. 845 11

Scavenger receptors interact with a variety of modified proteins, mediate their endocytosis and degradation, and may play an important role in protein catabolism and pathogenic processes such as atherosclerosis, aging, and diabetes. Many scavenger receptors have been detected kinetically but few such binding proteins have actually been identified. Recently, we found that two membrane-associated proteins, gp30 and gp18, interact more avidly with albumins conformationally modified by chemical means or by surface adsorption to colloidal gold particles than with native albumin. In this study, we show that gp30 and gp18 behave similarly to other known scavenger receptors. Competition studies indicate a similar ligand binding profile to other known scavenger receptors. Polyanionic molecules (dextran sulfate, fucoidan, polyglutamic acid, polyinosinic acid, heparin) and modified albumins such as formaldehyde-treated or maleylated albumin (Mal-bovine serum albumin) competed with albumin conjugated to colloidal gold particles (A-Au) for the blotting of gp30 and gp18. A-Au and Mal-bovine serum albumin bound cultured endothelial cells with high affinity. Modified and native albumins were each internalized, but only modified albumins were then released degraded. Inhibition studies revealed that only the same molecules that were effective in blocking A-Au blotting of gp30 and gp18, also inhibited A-Au degradation. Addition of the lysosomotropic agent chloroquine resulted in more than 70% inhibition of degradation. Differential processing of A-Au by cultured smooth muscle and endothelial cells along with fibroblasts was observed in a manner consistent with gp30 and gp18 expression. Cumulatively, these results suggest that gp30 and gp18 may mediate the high affinity binding, endocytosis, and degradation of conformationally modified albumins but not native albumin.
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PMID:High affinity binding, endocytosis, and degradation of conformationally modified albumins. Potential role of gp30 and gp18 as novel scavenger receptors. 846 86

The widespread distribution of enzymes classed as semicarbazide-sensitive amine oxidases (SSAO enzymes) throughout a very wide range of eukaryotic as well as prokaryotic organisms encourages the aspirations of those who wish to demonstrate physiological, pathological or pharmacological importance. Such enzymes are found in several tissues of mammals, both freely soluble, as in blood plasma, and membrane-bound, for example, in smooth muscle and adipose tissue. While they are capable of deaminating many amines with the production of an aldehyde and hydrogen peroxide, doubt still surrounds the identity of the most important endogenous substrates for these enzymes. At present, methylamine and aminoacetone appear to head the list of candidates. The possibility that SSAO enzymes can convert amine substrates to highly toxic metabolites is illustrated by the production of acrolein from the xenobiotic amine, allylamine and formaldehyde and methylglyoxal from methylamine and aminoacetone, respectively. Activities of SSAO enzymes may be influenced by physiological changes, such as pregnancy or pathologically by disease states, including diabetes, tumours and burns. Increased deamination of aminoacetone by tissue and plasma SSAO enzymes as a result of its increased production from L-threonine in conditions such as exhaustion, starvation and diabetes mellitus may be harmful. Such dangers could be mitigated either physiologically by a compensatory reduction in SSAO activity or pharmacologically by treatment with inhibitors of SSAO.
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PMID:Some aspects of the pathophysiology of semicarbazide-sensitive amine oxidase enzymes. 858 67


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