Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the use of a 75 g oral glucose tolerance test, both insulin release (IRG) and the degree of peripheral sensitivity (SI) were evaluated simultaneously in groups with normal (NGT) and impaired (IGT) glucose tolerance as well as NIDDM. IRG was expressed as the ratio of the area under the insulin curve to that of the glucose curve above fasting levels. The peripheral glucose uptake rate (M) during the OGTT was measured as the difference between the glucose load and the increase in the amount of glucose in the glucose space during the oral glucose tolerance test (OGTT). SI was expressed as the ratio of the metabolic clearance rate (M/mean blood glucose) to log mean serum insulin. In the non-obese groups, both mean IRG and mean SI values were decreased with an increasing degree of hyperglycemia from NGT to NIDDM. Decreased mean SI values were also found in obese subjects. IGT-subjects given 3 months of diet and exercise achieved improved SI values. A non-obese NIDDM-group had higher mean IRG and mean SI values after 6 months of treatment with glipizide. The results were comparable to data obtained with more complicated techniques, such as the insulin clamp and suppression tests, and should be easy to apply on a large scale in epidemiological studies.
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PMID:Insulin release and peripheral sensitivity at the oral glucose tolerance test. 226 53

Non-insulin-dependent diabetes mellitus (NIDDM) is attributed to a failure of pancreatic beta cells to maintain insulin secretion at a level sufficient to compensate for underlying insulin resistance. In the ZDF rat, a model of NIDDM that closely resembles the human syndrome, we have previously reported profound underexpression of GLUT-2, the high-Km facilitative glucose transporter expressed by beta cells of normal animals. Here we report that islets of diabetic rats exhibit a marked decrease in the volume of GLUT-2-positive beta cells and a reduction at the electron-microscopic level in the number of GLUT-2-immunoreactive sites per unit of beta-cell plasma membrane. The deficiency of GLUT-2 cannot be induced in normal beta cells by in vivo or in vitro exposure to high levels of glucose nor can it be prevented in beta cells of prediabetic ZDF rats by elimination of hyperglycemia. We conclude that this dearth of immunodetectable GLUT-2 in NIDDM is not secondary to hyperglycemia and therefore that it may well play a causal role in the development of hyperglycemia.
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PMID:Evidence that down-regulation of beta-cell glucose transporters in non-insulin-dependent diabetes may be the cause of diabetic hyperglycemia. 226 45

Based on an analysis of data obtained in a group of 145 men and women with type 2 diabetes perssiting for 10.1 +/- 6.6 years who were hospitalized on account of unsatisfactory compensation of diabetes, the authors provided evidence that the fasting blood sugar level is associated with a reduced response of C peptide to an alimentary stimulus, while the excessive weight of the patients has a bearing on the elevated concentration of C peptide on fasting and causes their insulin resistance. The body weight has a bearing on the level of risk factors, i.e. HDL cholesterol, uric acid and in women also triacylglycerols. The elevated blood sugar level influences in a mirror image manner the sodium and potassium level. The relations between the blood sugar level and glomerular filtration draw attention to the interference with the water economy even at blood sugar levels which are still tolerated. The trend of rising potassium levels must be foreseen in case of a poor compensation even in case of insulin treatment of diabetes. The risk of elevated potassium should be taken into account also with regard to indications of antihypertensive treatment. The authors also draw attention to the need of acloser compensation of type 2 diabetes. Early adjustment of the energy metabolism in diabetics deserves priority. When insulin treatment is needed, the all-day requirement should be met by 2-3 doses.
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PMID:[The effect of elevated blood glucose levels and body weight on the metabolic profile in type 2 diabetes after long-term therapy]. 233 13

Increased hepatic glucose output is the main cause of fasting hyperglycemia in non-insulin dependent diabetes mellitus. Due to difficulties in obtaining a quantitative estimate of gluconeogenesis in vivo, the relative contribution of gluconeogenesis and glycogenolysis to this increased hepatic glucose output was unknown. The application in vivo of a new isotopic approach based on a mathematical model of the Krebs cycle enabled us to obtain a quantitative estimate of gluconeogenesis in vivo. Using this approach, gluconeogenesis was found to account for approximately 28% and approximately 97% of overall hepatic glucose output in healthy volunteers in the postabsorptive and in the fasted state respectively. When this technique was used to compare gluconeogenesis rates in non-insulin dependent diabetes mellitus and nondiabetic patients, gluconeogenesis was found to be increased threefold in the patients with non-insulin dependent diabetes mellitus (12.7 +/- 1.6 mu vs 3.6 +/- 0.6 mumol/Kg/min) and to be significantly correlated with fasting plasma glucose. Furthermore, the increase in gluconeogenesis could explain more than 80% of the increase in overall hepatic glucose output in patients with non-insulin dependent diabetes mellitus. In conclusion, in non-insulin dependent diabetes mellitus, gluconeogenesis, as measured by a new isotopic technique, is increased and this increase represents the main cause for increased overall hepatic glucose output and fasting hyperglycemia.
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PMID:Contribution of gluconeogenesis to overall glucose output in diabetic and nondiabetic men. 239 54

We have proposed that chronic hyperglycemia causes the abnormal glucose influence on arginine-stimulated insulin secretion in the neonatal streptozocin (STZ) rat model of NIDDM and therefore studied the effect of 24 h of mild insulin-induced hypoglycemia on this defect. Ultralente insulin, 20 U/kg, was given at 9 a.m. and 10 U/kg at 5 p.m., and insulin and glucagon secretion were then studied the next morning using the in vitro isolated, perfused pancreas. The fed plasma glucose concentrations decreased in the STZ rats from 191 +/- 13 to 101 +/- 9 mg/dl and from 133 +/- 4 to 99 +/- 8 mg/dl in the controls. As expected, 10 mM arginine caused a trivial insulin response at 2.8 mM glucose in the treated and untreated control groups compared with the marked one at 16.7 mM. The response to arginine at 2.8 mM glucose in the untreated STZ rats, however, was strikingly elevated (7.65 +/- 2.29 versus 0.41 +/- 0.16 ng/ml in the untreated controls) and it was not potentiated by the high glucose background, but the result at 2.8 mM glucose in the treated STZ rats was similar to that of the treated controls (0.46 +/- 0.12 versus 0.16 +/- 0.03 ng/ml). A return of glucose influence on IBMX-stimulated insulin secretion was also noted. Glucose-induced insulin release, however, was not restored in the treated STZ rats, but it was markedly suppressed in the controls by the insulin treatment. Glucose influence on the glucagon response to arginine was maintained in the STZ model even though the glucagon release to a lowered glucose concentration was lost.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormal insulin secretion in a streptozocin model of diabetes. Effects of insulin treatment. 240 48

Diabetes mellitus in the elderly is mainly of the non-insulin dependent type (NIDDM). A large proportion of such patients are treated with insulin, after many years of therapy with oral hypoglycemic agents (OHA), on the assumption that these lose their efficacy with time. Moreover, many such patients are obese and show preserved insulin release. In the present study 45 obese subjects with NIDDM (14 under good metabolic control and 31 who presented hyperglycemia for at least 3 mo prior to testing) were placed on a strictly hypocaloric diet (800 Kcal/d) for 20 to 24 d. All of these patients had preserved insulin release. At the end of the trial, all the patients presented a significant reduction in body weight and a near normalization of the blood glucose profile, as well as a significant decrease both in the serum cholesterol and triglyceride levels and in the systolic blood pressure. On the basis of these results, insulin and OHA could be reduced in all the patients and suspended in some of these. The decrease in blood glucose levels was the same in all the patients regardless of the length of time that each had suffered from NIDDM. Five non-obese patients were placed on the same regimen, but the daily insulin dose could not be reduced. These data indicate that the majority of obese elderly patients with NIDDM are unnecessarily treated with insulin or with OHA, while diet alone would be sufficient to keep them under good metabolic control.
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PMID:Insulin requirement in elderly patients with non-insulin dependent diabetes mellitus (NIDDM). 248 6

The effects on cardiac function of feeding a diet high in sucrose to male Wistar rats over an extended period of time (15 months) was examined. This diet produced a diabetic condition which resembled noninsulin dependent diabetes mellitus. Resting hyperglycemia, high circulating insulin and triglyceride levels were observed in these animals. Further, the sucrose fed animals were overweight in comparison to chow fed control animals. Contractile protein Ca2+-ATPase activity was measured as a biochemical estimate of cardiac contractile function. Myosin and actomyosin Ca2+-ATPase activities of isolated myofibrillar fractions from hearts of experimental animals were depressed in comparison to chow fed control rats. Myosin K+-EDTA activity was also altered. The results demonstrate for the first time a defect in contractile protein Ca2+-ATPase activity in rat hearts using a model of noninsulin dependent diabetes mellitus. As the animals were euthyroid, thyroid hormone alterations in these animals were unlikely to influence the results. The results also demonstrate that insulin could not be a direct factor associated with cardiac pathology in diabetes. Instead, cardiac dysfunction may be associated with other, as yet undefined, metabolic abnormalities which accompany the diabetic state.
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PMID:Cardiac contracile protein ATPase activity in a diet induced model of noninsulin dependent diabetes mellitus. 252 35

The study of G6Pase and GK activities in human liver (needle biopsies) in overnight fasted obese NIDDM patients has shown that, while G6Pase was unchanged, GK was higher (+ 55%, P less than 0.05) than in control subjects. Consequently, the G6Pase/GK ratio (which roughly reflects hepatic glucose production) was significantly reduced (-36%) in the obese diabetic group, due to more GK activity (glucose uptake). This contrasts with the activity in IDDM and nonobese NIDDM patients (where the G6Pase/GK ratio is elevated and normal, respectively) and would suggest that in the obese diabetic subjects, hepatic glucose production is not a major factor contributing to the maintenance of hyperglycemia in the overnight fasting state (leaving peripheral insulin resistance as the major cause of hyperglycemia).
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PMID:The glucose-6-phosphatase/glucokinase ratio in the liver of obese-diabetic subjects. 254 Jul 81

Obesity is associated with insulin resistance and type II diabetes mellitus. In the present study, we have characterized hepatic insulin receptor function in two animal models of obesity: the Zucker fatty rat (ZFR), a model of genetic obesity with severe hyperinsulinemia, and the Sprague-Dawley rat with dietary obesity, a model of acquired obesity. Zucker fatty rats were also treated with streptozotocin (STZ) in an effort to examine the effects of relative insulin deficiency and hyperglycemia in the setting of obesity. Using wheat germ agglutinin-purified insulin receptor extracted from liver, no significant difference in insulin binding was identified in either model of obesity. beta-Subunit autophosphorylation was significantly decreased in both obese models relative to that in controls (72% in the obese ZFR and 49% in the overfed Sprague-Dawley model). Kinase activity, as measured by phosphorylation of the 1142-1153 synthetic peptide, was also decreased in both models of obesity by 22% and 64%, respectively. In the Zucker rat, STZ treatment led to an 80% increase in receptor concentration and a further 70% increase in beta-subunit autophosphorylation per receptor, whereas tyrosine kinase activity toward substrate was not altered. Since kinase activity is closely linked to autophosphorylation, we determined the fraction of autophosphorylated (activated) receptors vs. non-phosphorylated (inactive) receptors by using antiphosphotyrosine antibody to precipitate receptors bound with [125I]insulin. There was no significant difference in the percentage of activated insulin receptors in the dietary obese, ZFR, or STZ-treated Zucker rat vs. that in the controls. In all models, the percentage of activated receptors ranged from 32-46% of the total receptor pool. These data suggest that in genetic and acquired obesity, autophosphorylation of the beta-subunit is reduced and is a limiting factor in insulin receptor activation. A similar fraction of all receptors appears to undergo some level of autophosphorylation; however, full autophosphorylation and, thus, activation of the receptor do not occur, and this results in a decrease in kinase activity. This block in autophosphorylation may account for significant reductions in insulin receptor kinase function in obesity.
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PMID:Alterations in the hepatic insulin receptor kinase in genetic and acquired obesity in rats. 255 53

We evaluated the prevalence of peripheral neuropathy by clinical and electrophysiological criteria and the prevalence of autonomic parasympathetic nerve dysfunction by heart-rate variation during deep breathing (expiration-to-inspiration ratio [E:1]) in 132 newly diagnosed non-insulin-dependent diabetic (NIDDM) subjects aged 45-64 yr and 142 randomly selected nondiabetic control subjects. The relationship of nerve dysfunction to the degree of hyperglycemia and insulin-secretion capacity were also investigated. Single and scattered symptoms and signs of peripheral neuropathy were found in both diabetic and control subjects. Symptomatic polyneuropathy was found in 1.5% of diabetic subjects but none of the control subjects. Polyneuropathy defined by clinical signs was found in 2.3% of the diabetic subjects and 1.4% of the control subjects. No subjects with both symptoms and signs were seen. Nerve conduction velocities (NCVs) were significantly slower in diabetic than control subjects. Polyneuropathy according to electrophysiological criteria was found in 15.2% of diabetic subjects but was not found in any control subjects. Electromyographic abnormalities were more common in diabetic than control women, but not significant differences were found in men. The resting heart rate was higher in diabetic than control women, but no significant difference was found in men. The mean E:I was significantly lower in diabetic men and women than control men and women. An abnormally low E:I was found in 9.2% of the diabetic men, 3.3% of the control men, 3.3% of the diabetic women, and none of the control women. NCV parameters, but not E:I, were inversely correlated with fasting blood glucose and glycosylated hemoglobin levels. A positive correlation between NCV and fasting and postglucose serum insulin levels was found in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of neuropathy in newly diagnosed NIDDM and nondiabetic control subjects. 255 61


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