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

Additions to the categorisation of the forms of diabetes, new knowledge about genetic facts and facts of immunology concerning heredity, etiology and pathogeny of the diabetes are very important for the innovations as well as the utilization of screenings for type I an type II diabetes. As for the laboratory examinations, the proof of the glucose fixed to the hemoglobin or to the albumin of the plasma has become important. The importance of the intensified insulin therapy with the technical support of pumps or injection facilities is emphasized with reference to the hyperinsulinism as one risk. The therapies with immune suppressive, with inhibitors of glucosidase and aldose-reductase and with the transplantation of pancreas or Langerhans' cells promise enormous improvements in the course of diabetes.
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PMID:[Current aspects of diagnosis and therapy of diabetes mellitus]. 179 34

Diabetes is characterized by hyperphagia, polydipsia, polyuria, and elevations in blood and urinary glucose. It has also been documented that beta-adrenergic responsiveness is reduced in diabetes. The intestinal glucosidase inhibitor, acarbose (BAY G 5421), decreases postprandial glycemia by delaying carbohydrate absorption. The purpose of this study was to evaluate the effects of chronic acarbose treatment (20 and 40 mg/100 g of diet) on the metabolic and adrenergic parameters altered in streptozotocin (STZ) (50 mg/kg, intravenously [IV] )-induced diabetes. Metabolic parameters were measured daily for 8 weeks. Diabetic rats were hyperphagic, polydipsic, and polyuric within 1 week of STZ treatment. Acarbose treatment did not consistently effect the food intake but did reduce water intake, urinary output, blood glucose, and the urinary loss of glucose associated with STZ-induced diabetes. Adrenergic responses were assessed by monitoring the increase in tail skin temperature (TST) associated with administration of isoproterenol. Diabetic rats were less responsive than controls and acarbose treatment restored responses toward that of the controls. Additionally, 3H-NE release from the tail artery was elevated in the diabetic rat and restored to normal in the acarbose-treated animals. Collectively these data suggest that acarbose treatment is effective in reducing the severity of metabolic and autonomic complications associated with STZ-induced diabetes.
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PMID:Beneficial effects of dietary acarbose in the streptozotocin-induced diabetic rat. 196 Nov 20

Acarbose (O-4,6-dideoxy-4-[[(1S, 4R, 5S, 6S)-4,5,6-trihydroxy-3- (hydroxymethyl)-2-cyclohexen-1-yl]amino]-a-D-glucopyranosyl-(1---- 4)-O-a-D- glucopyranosyl-(1----4)-4-glucopyranose, Bay g 5421), an a-glucosidase inhibitor from Actinoplanes, has been developed for the treatment of diabetes mellitus. To investigate the pharmacokinetics and the biotransformation, 14C-labelled acarbose ([14C]Bay g 5421) was required. About 37 GBq (1 Ci) D-[U-14C]glucose was used as a precursor to obtain [14C]acarbose with a radiochemical yield of between 1.58 and 2.56%. For fermentation purposes resting cells of the Actinoplanes mutant SN 1667/47 were used under cometabolism conditions with a 10-fold excess of maltose. The specific radioactivities achieved in individual preparations were 7.77 MBq/mg (210 microCi/mg), 8.03 MBq/mg (217 microCi/mg), and 9.14 MBq/mg (247 microCi/mg), with a radiochemical purity of greater than 98% in each case. By hydrolysis and subsequent investigation of the hydrolysis products it was shown that [14C]carbon atoms originating from the radioactive glucose are present only in the core and not in the maltose unit of [14C]acarbose.
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PMID:Radiosynthesis of [14C]acarbose. 261 Jul 16

Acarbose, a potent alpha-glucosidase inhibitor, represents a new concept for the treatment of metabolic disorders, and particularly diabetes mellitus. It slows the absorption kinetics of dietary carbohydrates by reversible competitive inhibition of alpha-glucosidase activity, and so reduces the post-prandial blood glucose increment and insulin response. For these reasons, the drug has been successfully used not only in the treatment of type I or type II diabetes, but also in the management of reactive hypoglycemias and dumping syndrome. In addition, some data suggest a possible role in the treatment of type IV hyperlipidemia. Because of the delay in absorption of oligo- and disaccharides resulting from its administration, a colic bacterial fermentation occurs, accounting for the frequent abdominal discomfort mentioned by the patients. These side effects would be lessened with the second generation glucosidase inhibitors now in progress.
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PMID:[Alpha-glucosidase inhibitors: a new therapeutic approach in diabetes and functional hypoglycemia]. 267 46

Postprandial hyperglycemia in diabetic patients can be modified by delaying the digestion and/or absorption of dietary carbohydrates. We have studied an orally active alpha-glucosidase inhibitor, Bay 1099, in normal volunteers to determine whether these inhibitors can decrease postprandial rises in serum glucose without causing gastrointestinal symptoms or significant fecal caloric wastage. Six subjects were given 25, 50, or 100 mg of Bay 1099 or placebo before meals for 1 week, each with a 1-week washout period. Fasting and postprandial concentrations of glucose, insulin, glucagon, enteroglucagon, and gastrointestinal inhibitory peptide (GIP) were measured after the first and last dose of Bay 1099, and the fecal excretions of protein, fat, fiber, and total calories were measured on the last three days of each diet. The passage of unabsorbed carbohydrate into the colon was determined by breath hydrogen analysis three times during each study week. Increasing doses of Bay 1099 were found to decrease the postprandial rise in serum glucose concentration, delay the time to peak insulin concentration, and decrease the output of GIP after the meal. No adaptation was apparent after 1 week of therapy. A dose of inhibitor (50 mg tid), which greatly improves postprandial glucose and hormone output in diabetes, was associated with minimal symptoms and no excess fecal caloric losses. Thus, glucosidase inhibitors such as Bay 1099 may be useful in the management of patients with carbohydrate intolerance.
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PMID:Intestinal and metabolic responses to an alpha-glucosidase inhibitor in normal volunteers. 305 29

To confirm findings obtained from animal experiments demonstrating the metabolic effect of two new glucosidase inhibitors, 7 single blind cross-over studies with 42 healthy male volunteers were performed. In each group 6 subjects received 25, 50, 100 and 200 mg BAY m 1099 and 10, 20, and 40 mg BAY o 1248 or placebo with a standardized breakfast. Blood glucose and serum insulin were measured in venous blood before and 30, 60, 90, 120 and 180 min after each of 3 meals. ECG, blood pressure, body weight, monitor ECG and haematological and clinico-chemical parameters were also examined. The postprandial increase in blood glucose and serum insulin after breakfast were significantly and dose-dependently reduced by BAY m 1099. 10 and 20 mg BAY o 1248 not only reduced the increases in blood glucose and serum insulin after breakfast, but also after lunch (10 mg). 40 mg BAY o 1248 prevented the postprandial increase in both metabolic parameters after breakfast (p less than 0.05), an effect which was sustained after lunch. Intestinal problems occurred (flatulence, meteorism, diarrhoea) in 25 of 42 volunteers. Objective tolerability was good. The results of these first clinical pharmacological studies with two new glucosidase inhibitors justify studies on patients with diabetes mellitus.
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PMID:The effect of new alpha-glucosidase inhibitors (BAY m 1099 and BAY o 1248) on meal-stimulated increases in glucose and insulin levels in man. 351 75

Sulfonylureas are the most potent and widely used oral antidiabetic agents. Despite the finding of possible side effects in a large multicenter trial (UGDP Study) demonstrating increased cardiovascular mortality during tolbutamide therapy, prescription of sulfonylureas has not declined in view of the inconclusive results of the study. In addition, new aspects of their mode of action have been discovered. Sulfonylureas may enhance insulin sensitivity of peripheral tissues, particularly by raising the decreased number of insulin receptors in type II diabetics. While this extrapancreatic effect appears to be quantitatively important, it is only present when insulin secretion is simultaneously stimulated. Insulin release is enhanced due to an increase in the sensitivity of the B-cell to glucose challenge. There is evidence to suggest that the extrapancreatic effect of sulfonylureas is secondary to their pancreatic effect. Pointers in the same direction emerged from our own results in a study on the influence of sulfonylureas added to insulin therapy on insulin sensitivity in type I diabetics. Sulfonylureas failed to increase insulin sensitivity and insulin requirements in these patients. The first generation compounds of sulfonylureas are associated with more side effects and drug interactions than the second generation preparations. However, the latter are more frequently associated with hypoglycemia since they are more potent and have a prolonged duration of action. Biguanides have almost fallen into disuse as therapeutic agents due to the potentially lethal complication of lactic acidosis. Only metformin may still be indicated in certain cases. Inhibitors of intestinal amylase and glucosidase represent a new therapeutic principle in diabetes therapy whose aim is to reduce postprandial hyperglycemia. Their value as therapeutic agents is not yet clearly established.
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PMID:[Oral antidiabetic agents: recent aspects]. 619 88

12 months therapy with acarbose in 143 type I and type II patients markedly improved the metabolic control, assessed by fasting and postprandial blood glucose determination. During 5 year acarbose treatment GIP levels were decreased and enteroglucagon levels were elevated. After withdrawal of the drug for one week GIP levels increased and enteroglucagon concentrations fell. Thus, GI-hormone changes were reversible after discontinuation of acarbose. Tolerability of acarbose was good and clinical chemistry and haematology parameters showed no changes after 1-5 years acarbose therapy. Approximately 60% of the patients had intestinal symptoms which subsided again for most patients after 1-4 weeks therapy with acarbose. Body weight remained unchanged. The glucosidase inhibitor acarbose is a new effective and safe therapeutic concept in the treatment of diabetes mellitus.
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PMID:Long-term treatment in diabetics with acarbose, a glucosidase inhibitor: efficacy, tolerability and effect on GI hormones. 639 44

In the past history of the pharmaceutical industry, secondary metabolites have been screened almost exclusively for antimicrobial activities. This biased and narrow view has severely limited the potential application of microbial metabolites. Fortunately, this situation is changing and we are now entering into a new era in which microbial metabolites are being applied to diseases heretofore only subjected to synthetic compounds. This new approach is the application of microbial secondary metabolites to diseases that are not caused by other bacteria or fungi. For years, major drugs such as hypotensive and anti-inflammatory agents that are used for non-infectious diseases have been strictly synthetic products. Similarly, major therapeutics for parasitic diseases in animals (for example, coccidiostats and anthelminthics) resulted strictly from screens of chemically synthesized compounds followed by molecular modification. However, today fermentation products such as monensin and lasalocid dominate the coccidiostat market. The avermectins, another group of streptomycete products, have high activity against helminths and arthropods. Indeed, their activity appears to be an order of magnitude greater than previously discovered anthelminthic agents, the vast majority of which are synthetic compounds. Umezawa's group in Japan has isolated many microbial products with important pharmacological activities by screening with simple enzymic assays. There is much interest in a natural inhibitor of intestinal glucosidase, which is produced by an actinomycete of the genus Actinoplanes. The aim is to decrease hyperglycaemia and triacylglycerol synthesis in adipose tissue, liver and the intestinal wall of patients with diabetes, obesity and type IV hyperlipidaemia. Another natural compound of interest is mevinolin, a fungal product which acts as a cholesterol-lowering agent in animals. Mevinolin is produced by Aspergillus terreus. In its hydroxyacid form (mevinolinic acid), mevinolin is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase from liver. It is clear that, although the microbe has contributed greatly to the benefit of mankind, we have merely scratched the surface of the potential of microbial activity.
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PMID:A new era of exploitation of microbial metabolites. 640 Apr 79

The alpha-glucosidase specific for the hydroxylysine-linked disaccharide units of collagens (or 2-0-alpha-D-glucopyranosyl-5-0-beta-D-galactopyranosylhydroxy-L-lysine glucohydrolase) has been measured in kidney cortex and brain cortical tissue of streptozotocin diabetic rats after 19, 23 or 28 weeks of diabetes and of aged rats 22 months old. Increased specific activities of the enzyme have been found repeatedly in the dialyzed homogenates and the 7.2 X 10(6) g.min supernatants of kidney and brain at the various stages of diabetes when compared with age-matched controls; the specific activities returned to a normal level after insulin treatment. Similar increased specific activities were observed in kidney and brain of the aged normoglycemic rats when compared with young adult rats. In diabetic kidney cortex, beta-galactosidase and p-nitrophenyl-alpha-D-glucoside glucosidase specific activities were decreased in contrast to the increase of glucosyl-galactosyl-hydroxy-lysine glucohydrolase. In kidney cortex of the aged rats, beta-galactosidase activity was also decreased, but p-nitrophenyl-alpha-D-glucoside glucosidase was increased. In both diabetic and aged rats, thickening of the kidney glomerular basement membranes was confirmed; thickening of the brain cortical capillary basement membranes was also observed. Thus in the diabetic and aged animals, the increased glucosyl-galactosyl-hydroxylysine glucohydrolase specific activity was associated with basement membrane thickening in the kidney and the brain.
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PMID:Studies on the alpha-glucosidase specific for collagen disaccharide units: variations associated with capillary basement membrane thickening in kidney and brain of diabetic and aged rats. 716 52


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