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

Microvessels in the cheek pouch of the hamster were investigated to determine their structural, reactivity, and permeability characteristics after the induction of diabetes. To induce diabetes, hamsters were injected with streptozotocin (50 mg/kg body wt./day, i.p., for 3 days). Vehicle-injected, age-matched hamsters were the controls. Diabetic hamsters were characterized by elevated serum glucose (greater than 300 mg/dl) and triglycerides and decreased serum insulin (50%). Microvascular studies were completed on cheek pouch microvessels suffused with Ringer's solution (37 degrees C, pH 7.4) bubbled with 95% N2-5% CO2. Vascular dimensions and reactivity of selected arterioles and venules to microapplications of norepinephrine were determined with a video micrometer using intravital microscopy. Restrictiveness of the microvascular membranes to fluorescein-labeled dextran fractions (mol wt: 150,000; 40,000; 20,000 daltons) was measured by determining the number of leaky sites. Stimulation of membrane permeability by histamine was investigated. There were no major alterations in arteriolar lumen and wall diameters, whereas venular lumen diameters were increased in hamsters diabetic for two months. Likewise, arteriolar responses to norepinephrine were not altered by diabetes; however, venular responses were decreased at two months. The restrictiveness of the vascular membrane to various dextran fractions was dramatically decreased in the diabetic animals at two months. Histamine did not alter microvascular leakage in the diabetic as it did in the normal hamsters. These studies indicate that microvascular alterations, venular dilation, and increased permeability to large molecules occur in the diabetic hamster within two months after the induction of diabetes.
Diabetes 1981 Feb
PMID:Microvascular alterations develop in Syrian hamsters after the induction of diabetes mellitus by streptozotocin. 616 95

1. Rat liver endoplasmic reticulum catalyzes the reduction of 4-dimethylaminoazobenzene (DAB) by NADPH to dimethyl-p-phenylenediamine and p-aminophenol. This azoreductase activity was inhibited by cyanide and cytochrome b5 antibody, but was resistant to carbon monoxide and SKF-525A (beta-diethylaminoethyl-diphenylpropylacetate). 2. DAB azoreductase activity was induced by 20-methylcholanthrene and phenobarbital, and increased in streptozotocin-induced diabetes or fasting. It was repressed by treatment with DAB and its 3'-methyl derivative, but not by several other derivatives with substitutions in the dimethylaminoazobenzene ring. 3. Azoreductase activity, NADPH-cytochrome P-450 reductase, cytochromes P-450 and b5 were measured in liver microsomes prepared from fasted animals and from animals treated with 20-methylcholanthrene, phenobarbital, streptozotocin or 3-aminotriazole plus allyl-isopropylacetamide. No direct correlation could be established between the variations of azoreductase activity and those of cytochromes P-450 and b5, and of NADPH-cytochrome P-450 reductase in these experimental situations. Since these known carriers do not seem to be the limiting factors for the azoreductase activity, the participation of an unknown carrier that can be repressed by dimethylaminoazobenzene is postulated. 4. Dimethylaminoazobenzene treatment did not reduce the rate of synthesis of microsomal proteins but rather increased the turnover rate of proteins with molecular weights of about 17, 30 an 35 kdal. Since streptozotocin increased the synthesis of proteins with molecular weights of 17, 32, and 48 kdal it is suggested that one of these proteins may correspond to the postulated carrier that is the limiting factor in DAB reduction.
 ...
PMID:Effect of drugs and hormones on rat liver dimethylaminoazobenzene reductase activity. 621 56

Nine non-insulin-dependent diabetics were studied before and after 3 weeks on an isoenergetic high-fiber/high-starch/low-fat diet (alternative diet), and nine non-insulin-dependent diabetics were studied on their usual diet. In the group that ate the alternative diet, the intake of fiber and starch increased 120% and 53%, whereas fat intake decreased 31%. Diabetes control improved as demonstrated by decreased fasting plasma glucose (P less than 0.05) and 24-hour urinary glucose excretion (P less than 0.05). The in vivo insulin action increased (KIVITT increased, P less than 0.05) with no change in fasting serum insulin levels. In fat cells obtained from patients in the alternative-diet group, insulin receptor binding increased (P less than 0.05) after the change of diet. Insulin binding to purified monocytes (more than 95% monocytes) also increased (P less than 0.05), whereas no change was found in insulin binding to erythrocytes. When lipogenesis was studied at a tracer glucose concentration at which glucose transport seems to be rate limiting, insulin sensitivity increased (P less than 0.02). This is the predicted consequence of increased receptor binding. Moreover, when CO2 production and lipogenesis were studied at a higher glucose concentration, where steps beyond transport seem to be rate limiting for glucose metabolism, increased insulin sensitivity was also observed. In contrast, no change was found in maximal insulin responsiveness. Fat and blood cells from the patients who continued on their usual diet showed no changes of the mentioned quantities.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Increased insulin binding to adipocytes and monocytes and increased insulin sensitivity of glucose transport and metabolism in adipocytes from non-insulin-dependent diabetics after a low-fat/high-starch/high-fiber diet. 631 51

To assess possible cellular mechanisms of in vitro resistance in noninsulin-dependent diabetes mellitus (NIDDM), maximum insulin-stimulated glucose transport and utilization and insulin binding were measured in adipocytes isolated from weight-matched normal glycemic subjects and patients with NIDDM. Glucose transport rate was determined by measuring the amount of [U-14C]-D-glucose taken up by incubating adipocytes at trace concentrations of glucose (300 nM), and glucose metabolism by estimating the amount of lactate, CO2, triglyceride, and total glucose carbons retained in the cells following incubating at 5.5 mM glucose. Insulin binding was measured at 50, 100, and 200 pM [mono125I-tyrosinyl A14]insulin. Both maximum insulin-stimulated glucose transport and utilization in adipocytes from diabetic subjects were 40% (P less than 0.01) and 32% (P less than 0.05) lower, respectively, than values obtained for subjects with normal glucose tolerance. In addition, the maximum capacity of glucose transport was correlated with the maximum capacity of glucose utilization (r = 0.81, P less than 0.001). Furthermore, fasting plasma glucose concentrations of diabetic subjects were negatively correlated with both maximum insulin-stimulated glucose transport (r = -0.56, P less than 0.05) and glucose utilization (r = -0.67, P less than 0.05). Since basal glucose transport in adipocytes from diabetic subjects was also 33% lower than in adipocytes from normal subjects, there was no change in the relative ability of insulin to stimulate glucose transport. However, there was a 64% decrease in the sensitivity of the glucose transport system to insulin (P less than 0.05), unrelated to concomitant changes in insulin binding. These results demonstrate that both maximal insulin-stimulated glucose transport and utilization, and the sensitivity of the glucose transport system to insulin, was decreased in adipocytes isolated from subjects with NIDDM. These in vitro defects were associated with impaired glucose metabolism in vivo, consistent with the view that the metabolic alterations observed at the cellular level may contribute to the in vivo insulin resistance of NIDDM.
 ...
PMID:In vitro insulin resistance of human adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus. 635 80

It has been previously reported that maximum insulin-stimulated glucose transport and utilization were both decreased, while basal lipolysis was increased in adipocytes from obese subjects with noninsulin-dependent diabetes mellitus (NIDDM). To determine whether these values can be returned towards those obtained in equally obese subjects with normal glucose tolerance, these measures of adipocyte metabolism were quantified in 10 NIDDM subjects before and after control of hyperglycemia with insulin. The results demonstrate that maximum insulin-stimulated glucose transport (P less than 0.02) and glucose incorporation into triglyceride (P less than 0.01) and CO2 (P less than 0.05) (at 5.5 mM glucose) increased and basal lipolysis decreased (P less than 0.05) after 4 wk of insulin treatment. In contrast, glucose incorporation into lactate and other glycolytic metabolites (at 5.5 mM glucose), and sensitivity of glucose transport to insulin, did not improve with insulin therapy. The latter occurred despite an increase in insulin binding (P less than 0.01). Finally, the improvement in maximal insulin-stimulated glucose transport correlated with the fall in fasting hyperglycemia (r = 0.77, P less than 0.01). These findings demonstrate that several of the abnormalities of carbohydrate and lipid metabolism recently noted to be present in adipocytes from patients with NIDDM can be shown to significantly improve with insulin treatment.
 ...
PMID:Improvement in in vitro insulin action after one month of insulin therapy in obese noninsulin-dependent diabetics. Measurements of glucose transport and metabolism, insulin binding, and lipolysis in isolated adipocytes. 635 58

Sprague-Dawley male rats were injected at 2 days of age with streptozotocin (SZ). At 4 wk of age the fed plasma glucose concentration of the SZ group was 151 +/- 6 mg/dl as compared with 133 +/- 4 for the control group. The fed plasma insulin values were indistinguishable, however. In response to an intraperitoneal glucose challenge the SZ group had marked glucose intolerance and virtually no rise in plasma insulin. After a meal challenge the SZ group also had glucose intolerance, but plasma insulin responses were similar to those of the control. The pancreata of the 4-wk-old rats were perfused in vitro and the SZ group had essentially no response to glucose, but did respond to arginine. Adipocytes of the 4-wk-old SZ rats had impaired glucose conversion to CO2 similar to that seen in the more hyperglycemic 6-wk-old SZ rats. Castration carried out at about 3 wk of age did not influence the hyperglycemia seen at 6 wk of age and later. These data indicate that 4-wk-old SZ rats, while having near-normal plasma glucose levels and normal plasma insulin values, have clearly abnormal B-cell and adipocyte function. With increasing age and weight gain these SZ rats develop frank hyperglycemia.
Diabetes 1984 Feb
PMID:Abnormal islet and adipocyte function in young B-cell-deficient rats with near-normoglycemia. 636 71

Pieces of rat epididymal fat tissue were maintained in a biochemically defined medium for 20 to 44 hours in either the absence or presence of a sulfonylurea at levels known to be effective in humans. Prolonged exposure of adipocytes to sulfonylureas did not influence the number of insulin receptors or their affinity to insulin or the ability of insulin to induce receptor loss (down-regulation). Also, the sulfonylureas did not influence the basal uptake of the D-glucose analogs 2-deoxyglucose and 3-O-methylglucose. However, exposure to these drugs resulted in a potentiation of the stimulatory effects of insulin on hexose transport at submaximal and maximally effective concentrations of insulin. The average potentiation was approximately 30%. In addition, sulfonylureas enhanced stimulation of hexose uptake by the insulin mimickers, hydrogen peroxide and vitamin K5. These oxidants are known to manifest insulin-like actions subsequent to insulin binding. Under conditions in which glucose transport was rate limiting, the conversion of glucose to carbon dioxide and the total lipids mirrored the findings of hexose uptake. However, at a glucose concentration of 50 mM, at which hexose transport is no longer rate limiting, sulfonylureas did not potentiate metabolism in th absence or presence of insulin. These results may help to explain the hypoglycemic action of the drug in view of the recent finding that a postreceptor deficit is present in noninsulin-dependent diabetes mellitus.
 ...
PMID:Extrapancreatic effects of sulfonylureas. Potentiation of insulin action through post-binding mechanisms. 640 22

BALB/c female streptozotocin-diabetic mice were transplanted under the left kidney capsule with syngeneic or allogeneic CBA 17-day fetal pancreases that had been organ-cultured for 23 days. Two isografted groups received a single graft per recipient, cultured normally (90% air, 10% CO2), or in an oxygen-rich atmosphere (90% O2, 10% CO2): 13/14 and 12/13 respectively became normoglycemic. The 3rd and 4th groups were transplanted each with 1 and 3 allogeneic fetal pancreases per recipient, which had been cultured in 90% O2: 5/12 and 2/13 mice respectively had surviving allografts after 104 days, and 2/5 of the former and both of the latter had become normoglycemic. Five out of the seven surviving allografts contained foci of infiltrating lymphocytes. After removal of the kidneys containing the grafts, surviving mice were retransplanted under the right kidney capsule, each with 2 CBA fetal pancreases which had been cultured for only 4 days under normal conditions--hence they were fully immunogenic. Rejection of the secondary allografts was delayed in the long-term, primary allograft acceptors, suggesting that a degree of tolerance had developed. This study demonstrates that it is possible for a single, cultured fetal pancreas to survive indefinitely and reverse diabetes after transplantation to a fully allogeneic, nonimmunosuppressed recipient.
 ...
PMID:Reduction of the immunogenicity of fetal mouse pancreas allografts by organ culture in 90 percent oxygen. 641 3

We studied the glucose oxidation to CO2 and the incorporation of glucose into lipids by thoracic aorta from streptozotocin-diabetic rats in two circumstances: 9 minutes exposure of the isolated aorta to insulin, perfused in situ; and one-week treatment with either low--4 units (U)--or high--12 U--daily doses of insulin. Diabetes inhibited the glucose metabolism of media and adventitia. Perfusion with insulin did not influence the depressed metabolism of media but increased that of adventitia. Four units insulin treatment normalized the synthesis of glucose-derived lipids by the media, whereas 12-U treatment brought it to levels significantly higher (+23%) than those found in nondiabetic rats. We conclude that: (a) a haemodynamic explanation cannot account for the in vitro insulin resistance of media found in diabetes; (b) insulin treatment exerts a dose-dependent lipogenic effect upon the media, which might favour an atherogenic role for therapeutic hyperinsulinaemia in insulin-dependent diabetics.
 ...
PMID:Diabetes and insulin: actions and interactions upon the glucose metabolism of rat aorta. 643 Jul 29

Management of total parenteral nutrition (TPN) in depressed glucose metabolism was investigated clinically and experimentally in view of insulin control and/or new component of carbohydrate solution. Fifty TPN cases out of 837 for 9 years were successfully performed insulin control, while 17 patients were unable to get sufficient calory in spite of insulin administration. Cumulative expired CO2 after injection of radioactive carbohydrate in rats showed that each carbohydrate was utilized in the order of glucose, fructose, maltose, sorbitol and xylitol even in depressed glucose metabolism and that depressed carbohydrate metabolism was improved by adequate insulin injection. Combined use of glucose, fructose and xylitol at 4:2:1 (GFX) was was experimentally revealed to be superior to glucose alone as carbohydrate source of TPN in depressed glucose metabolism. Compared with conventional TPN (C-TPN), GFX-TPN showed lower blood glucose and insulin level in rabbits of sepsis and rats of streptozotocin diabetes. Contents of fructose 2,6 bisphosphate and triglyceride and activities of fructose 6 phosphate 2 kinase, acetyl CoA carboxylase and fatty acid synthetase in liver of these animals supported that GFX had favourable effects on glucose and fat utilization in depressed glucose Blood glucose of early postoperative patients was lower in GFX-TPN than in C-TPN.
 ...
PMID:[Keypoints and compositions of total parenteral nutrition for patients with low glucose tolerance levels]. 643 89


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>