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

The effects of sucrose and Acarbose (alpha-glucosidase inhibitor) feeding on the development of diabetes were studied in streptozotocin-treated rats. Rats were raised on four different dietary regimens, viz, a sucrose diet (46% of the total weight in the form of sucrose, 24% as starch), a starch diet (70% as starch), a standard diet (laboratory chow: Oriental Yeast Co.) or an Acarbose diet (a standard diet containing 75 mg Acarbose/100g diet) for a week followed by an intraperitoneal injection of streptozotocin (70 mg/kg). Development of diabetes was determined by urinary and blood glucose levels (more than 250 mg/dl). The incidence of diabetes in the groups of rats fed on sucrose, starch, standard, and Acarbose diets was 100%, 80%, 70% and 47.6%, respectively. The development of diabetes was accelerated by sucrose feeding and depressed by Acarbose feeding. There was mild diabetes in rats fed on Acarbose diet. The sucrose feeding caused a marked increase of disaccharidase activities in the proximal part of the intestine and in the apical part of the villus-crypt gradient of epithelial cells. The Acarbose feeding caused a significant decrease of disaccharidase activities. The changes in protein content of the sucrase-isomaltase complex appeared to be in parallel with those of disaccharidase activities. These results suggest that intestinal disaccharidase activities are involved in the development of experimental diabetes induced by streptozotocin.
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PMID:Effect of sucrose and Acarbose feeding on the development of streptozotocin-induced diabetes in the rat. 621 54

Acarbose, an alpha-glucosidase inhibitor, lowers the glycemic excursion following the ingestion of carbohydrates, in particular, sucrose. This was confirmed with increasing doses of acarbose (0, 50, and 100 mg) and the causes investigated. The absorption of the glucose moiety of sucrose was determined from plasma tracer concentrations when overnight-fasted normal subjects received a 100-g oral sucrose load labeled with sucrose [(1-14C]glucose and a simultaneous intravenous infusion of [3-3H]glucose. As the dose of acarbose given with the sucrose load was increased from 0 to 100 mg, the percentage of the load appearing in the peripheral circulation decreased from 90% to 62%. Malabsorption was confirmed by the appearance of breath hydrogen. Simultaneously, absorption time increased from 243 to 411 min. Maximal glycemic excursions were therefore lowered from 64 to 31 mg/dl. The plasma concentrations of gastric inhibitory polypeptide and insulin decreased with the acarbose dose so that the fractional disappearance rate of glucose also decreased. However, the concentrations of glucagon-like immunoreactivity (GLI) rose, confirming the ileal appearance of malabsorbed sucrose.
Diabetes 1984 Mar
PMID:The effects of an alpha-glucoside hydrolase inhibitor on glycemia and the absorption of sucrose in man determined using a tracer method. 636 57

The catalytic activities of N-acetyl-beta-D-glucosaminidase, beta-galactosidase and alpha-glucosidase in kidney and urine of diabetic rats were investigated in relation to the duration of diabetes, to the degree of constant hyperglycaemia and to the therapeutic control in the early stage of disease. The results suggest that the degree of constant hyperglycaemia and the duration of untreated diabetes are significant determining factors for the course of morphological changes. These changes are manifested as a decrease of the glycosidases in kidney (0.5 to 0.6 time the age-matched controls) and as moderate to severe enzymurias. Daily variation of blood glucose with inadequate insulin Lente therapy caused decreased N-acetyl-beta-D-glucosaminidase and beta-galactosidase activities in kidney as well as enzymuria. Since such changes can be correlated with histologically visible changes in the kidney, the measurement of these enzymes in urine is a simple way of monitoring the development of kidney damage in poorly controlled diabetes. When constant normoglycaemia was maintained for three weeks with insulin Ultralente in diabetic rats with a confirmed decrease of kidney glycosidases, the persisting morphological alteration of the organ was reflected by a urinary output of N-acetyl-beta-D-glucosaminidase.
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PMID:Effect of the degree of hyperglycaemia on the catalytic activities of glycosidases in kidney and urine of diabetic rats. 636 9

The postprandial blood glucose rise after a standard meal in six non-insulin dependent diabetics was significantly lower when acarbose 200 mg was taken together with the meal than without acarbose. Eight weeks acarbose treatment (300 mg), however, did not change fasting blood glucose. The effect of four weeks administration of the alpha-glucosidase inhibitor acarbose (300 mg) on diabetes regulation in another ten non-insulin dependent diabetics was compared with metformin (500 mg) in a double-blind cross-over study. Acarbose lowered postprandial blood glucose level from 11.5 +/- 4.2 to 8.9 +/- 1.8 mmol/l (p less than 0.02) and haemoglobin Alc from 8.1 +/- 1.8 to 7.7 +/- 1.7% (p less than 0.05). Urinary glucose was also decreased. Metformin did not significantly change postprandial blood glucose, haemoglobin A1c and urinary glucose excretion with the prescribed dose. The postprandial blood glucose and haemoglobin A1c after 4 weeks of treatment with acarbose and of metformin did not differ significantly. Side-effects of both drugs were mild and mainly gastrointestinal, but the frequency of side-effects was not different.
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PMID:Acarbose treatment of sulfonylurea-treated non-insulin dependent diabetics. A double-blind cross-over comparison of an alpha-glucosidase inhibitor with metformin. 639 73

Nocturnal hypoglycemia is common in the diabetic patient on twice-daily regular and intermediate (NPH or lente) insulin regimens because intermediate-acting insulins before the main evening meal produce "unopposed" free insulin peaks around 0300 h, food absorption having been completed much earlier. Fourteen insulin-dependent diabetic patients were treated for 6 wk with the alpha-glucosidase inhibitor, acarbose, in a double-blind crossover study to see whether the drug would delay absorption of the evening meal sufficiently to correct the mismatch and prevent nocturnal hypoglycemia. On 200 mg acarbose (six patients), inhibition of carbohydrate digestion was so profound as to lead to midevening hypoglycemia with severe flatulence and abdominal colic. With a smaller dose of 100 mg before the evening meal (eight patients) there was a significant reduction in MAGE and MBG coupled with a clinically significant reduction in midevening and nocturnal hypoglycemic reactions. Alpha-glucosidase inhibition therefore provides a promising new approach to the problem of nocturnal hypoglycemia although a preparation that is safe for long-term clinical use remains to be found.
Diabetes Care
PMID:A new approach to the treatment of nocturnal hypoglycemia using alpha-glucosidase inhibition. 640 Jul 9

The binding of the lectins concanavalin A (Con A) and wheat germ agglutinin (WGA) to the luminal surface of lung alveolar epithelial cells was compared in normal rats and rats with streptozotocin-induced diabetes and their offspring. Lung tissue was lavaged, then fixed in situ with 3% glutaraldehyde. Buffer-rinsed slices of lung were incubated in Con A, WGA, or various control media. Lectin binding sites were visualized by the use of the peroxidase method. Normal neonates and those that were the results of diabetic pregnancies showed a hexose-specific Con A and WGA binding pattern qualitatively similar to that of normal and diabetic adults, respectively. In the normal animals, Con A binding sites were masked by sialic acid residues and were removable with alpha-mannosidase after neuraminidase treatment. In the diabetic adults and their offspring, one the other hand, Con A binding sites were readily accessible and were totally removed only by sequential treatment with alpha-mannosidase and alpha-glucosidase. WGA binding was essentially eliminated with neuraminidase in all animals except in the neonates from diabetic pregnancies, where N-acetyl-glucosaminidase was also required. The effects of maternal diabetes were reversible and occurred about Day 7 postpartum in the neonate. The effects were also reversible following insulin replacement in the diabetic adult.
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PMID:Diabetic pregnancy. Changes in lectin binding to the surface of rat lung alveolar epithelial cells. 668 9

Acarbose is a newly developed inhibitor of intestinal alpha-glucosidase, and in the current study its ability to lower plasma glucose levels was studied in 12 patients with non-insulin-dependent diabetes mellitus, poorly controlled on diet plus sulfonylurea drugs. Patients were studied before and three months after the addition of acarbose to their treatment program, and there was a notable fall in postprandial plasma glucose concentrations that approximated 60 mg/dL. When acarbose therapy was discontinued in five patients, plasma glucose levels rapidly returned toward pretreatment levels. In addition to the improvement in glycemia, acarbose treatment also led to a notable reduction in Hb A1c and triglyceride concentrations. Finally, considerable individual variation was noted in the response to acarbose, and the results in four patients were quite dramatic, with striking reductions in both fasting and postprandial glucose concentrations. These data suggest that acarbose may be a useful addition in the treatment of patients with non-insulin-dependent diabetes mellitus.
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PMID:Acarbose treatment of non-insulin-dependent diabetes mellitus. 669 73

Recent investigations point to the nonenzymatic glycosylation as a cause of long-term complications in diabetes mellitus. We describe an enzymatic activity that cleaves glucose from the glomerular basement membrane (GBM), present in lysosomal preparations of diabetic lymphocytes. The GBM, nonenzymatically glycosylated or obtained from rats with diabetes, were incubated with enzyme preparations, separated on Sephadex G-25 and applied for glucose measurement on gas chromatography and mass spectroscopy. The lysosomal preparation of diabetic lymphocytes cleaved from rat GBM, which were nonenzymatically glycosylated 300-500 ng glucose/mg GBM protein, from diabetic rat GBM 300 ng glucose/mg GBM protein. A lysosomal preparation of normal lymphocytes failed to do so, indicating enzyme induction in the diabetic state. Control studies with the glycosylated hemoglobin AIc confirmed this finding and showed the specificity of the enzyme, as alpha-glucosidase and beta-glucosidase failed to cleave the N-glycosidic bond between glucose and the protein. The enzymatic activity can be described formally as a N-l-deoxyfructofuranosyl-glucohydrolase, which could be responsible for a potential reversibility of diabetic GBM changes.
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PMID:Enzymatic reversibility of nonenzymatic glycosylation of the glomerular basement membrane. Is the diabetic glomerulopathy principally reversible? 683 51

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

The present study was designed to determine the possible significance of a therapeutic dose (0.2 mg) of AO-128 on carbohydrate absorption by measuring the breath hydrogen concentration, which is an index of the amount of unabsorbed carbohydrate in the large intestine. Post-prandial hyperglycemia is common among diabetic patients. AO-128, a potent alpha-glucosidase inhibitor, suppressed post-prandial hyperglycemia and hyperinsulinemia in healthy volunteers at a dose of 0.2 mg with each meal. These volunteers increased the breath hydrogen concentration in response to ingestion of non-absorbable lactulose, but decreased only slightly its concentration from the basal level after sucrose ingestion, indicating complete absorption. When AO-128 (0.2 mg) was given with sucrose, hydrogen production increased only slightly compared with placebo, suggesting that the inhibitory effect of AO-128 on sucrose absorption was minimal. Only 5 g of the 100 g of sucrose was not absorbed and this 5% reduction is too small to explain the observed inhibitory effect on the post-prandial rise in plasma glucose. Sucrose loading in rats (about 443 mg) sharply increased blood glucose and was accompanied by the rapid disappearance of sucrose from the upper small intestine. AO-128 (0.03 or 0.1 mg/kg) lessened the elevation of blood glucose after sucrose ingestion. The lower dose (0.03 mg/kg) retarded small intestinal absorption, but did not induce an influx of sucrose into the cecum and large intestine, while the higher dose (0.1 mg/kg) caused an increased influx of sucrose into the large bowel. These results indicated that AO-128 retards the absorption of carbohydrate and reduces post-prandial hyperglycemia.
Diabetes Res Clin Pract 1995 May
PMID:An alpha-glucosidase inhibitor, AO-128, retards carbohydrate absorption in rats and humans. 758 23


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