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Query: UMLS:C0011860 (type 2 diabetes)
57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To gain insight into cellular events associated with the progression of obesity to diabetes, we have studied glucose metabolism and insulin responses in adipocytes from monkeys with spontaneous obesity. Over a 3- period, we studied animals which (A) remained relatively lean; (B) became obese (over 30 percent body fat) with normal glucose tolerance; (C) were obese and developed hyperinsulinemia (over 100 microU/ml); and (D) were obese and subsequently developed noninsulin-dependent diabetes (NIDDM) (fasting plasma glucose above 140 mg/dl and abnormal glucose tolerance test). Adipocyte glucose utilization, evaluated by conversion of 14-C-glucose to CO2 and lipids, was measured in the absence and presence of varying concentrations of insulin, using cells prepared from biopsy samples of subcutaneous abdominal fat. The major change in adipocyte metabolism was a decrease in basal and insulin-stimulated glucose utilization in NIDDM, relative to the enhanced responses observed in cells from the obese-hyperinsulinemic monkeys. Longitudinal studies of individual monkeys over 2-3 years led to the following additional observations regarding adipocyte glucose metabolism. Basal and insulin-stimulated glucose utilization dropped markedly as hyperinsulinemia progressed into diabetes. As impairments in glucose tolerance worsened in diabetes, adipocytes showed only a modest or negligible additional impairment in basal and insulin-stimulated glucose oxidation. Insulin binding was reduced in adipocytes from monkeys with obesity as compared to lean controls, and was similar in cells from monkeys with obesity and NIDDM. In the monkeys, obesity was initially associated with enhanced adipocyte metabolism. With the spontaneous development of NIDDM, glucose metabolism in adipocytes was depressed. The progression of metabolic events from hyperinsulinemia to NIDDM in monkeys includes cellular changes in insulin responses at the level of the adipocyte.
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PMID:Changes in insulin responses and binding in adipocytes from monkeys with obesity progressing to diabetes. 306 66

In type 2 diabetes with "secondary failure of sulfonylurea therapy" good metabolic control can seldom be achieved by insulin therapy even with high insulin doses. Hyperinsulinemia however is a possible risk factor of cardiovascular disease in type 2 diabetes. Maintaining the effects of sulfonylurea action insulin should be added in as small amounts as possible to avoid hyperinsulinemia and to ameliorate hyperglycemia. 16 type 2 diabetics with "secondary failure" were treated either with insulin alone (group A; n = 8) or with 3.5 mg b.i.d. glibenclamide plus small amounts of intermediate insulin (group B; n = 8) in a randomised order. After the inpatient period outpatient control was performed monthly up to six months, later on four times a year up to two years. Both groups were comparable with regard to age, duration of diabetes, body weight and metabolic control. The daily insulin dose was 14 +/- 2 IU (means +/- SEM) after one month and 19 +/- 2 IU after two years in group B. In contrast 30 +/- 3 IU and 43 +/- 5 IU respectively were needed in group A (p less than 0.001). All patients B were treated with one daily injection, all patients A needed two injections. Resulting in nearly identical metabolic control in group A basal insulin levels exceeded those in group B after two years significantly (28.6 +/- 3.7 vs. 18.6 +/- 1.6 mcU/ml; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Combination therapy with insulin/sulfonylurea in the long-term therapy of type II diabetes following "secondary failure"]. 314 87

Non-insulin-dependent diabetes (NIDDM) is a major cause of premature morbidity and mortality among adults. Macrovascular disease of coronary and peripheral vessels is the primary cause of death in these patients. Numerous experimental and epidemiologic studies have suggested that hyperinsulinemia accelerates the development of atherosclerosis. In experimental models, insulin promotes diet-induced lesion development and overrides lesion regression and estrogen protection against atherosclerosis. Local hyperinsulinemia induced by selected arterial infusion accelerates atherosclerosis in the perfused artery. Insulin has been shown to stimulate subintimal smooth muscle and fibroblast cells in culture, and to increase the uptake and local synthesis of lipid by these cells. Insulin may also induce inhibition of fibrinolysis. Several prospective studies performed on nondiabetic patients show that either fasting or postprandial insulin levels are a sensitive predictor of the development of coronary disease independent of other risk factors. Two recent studies in NIDDM patients confirm this finding and suggest that glycemic control may not be a significant factor in the development of macrovascular disease. Diseases of carbohydrate tolerance, ie, NIDDM, impaired glucose tolerance, obesity, are frequently associated with elevated circulating insulin levels, either physiologically or secondary to treatment. Given the high prevalence of cardiovascular disease in these populations, modifying therapy to minimize hyperinsulinemia should be an important consideration in a treatment program. Use of oral agents such as glipizide or gliclazide, which induce less diurnal hyperinsulinemia, may be advantageous when compared to traditional oral agent or insulin therapy.
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PMID:Atherosclerosis in diabetes: the role of hyperinsulinemia. 327 13

Toxemia of pregnancy is a perplexing clinical problem that has defied accurate elucidation of its etiology because the disorder does not occur in undisturbed lower mammalian species that are currently used as animal models of reproductive physiology. We propose that toxemia of pregnancy occurs as the end stage human fetal-placental unit response to decreased maternal uterine blood flow, and that this fetal-placental unit response may be unique to the human species. The human fetus increases insulin secretion in response to progressive intrauterine asphyxia, which may result in decreased fetal-placental prostacyclin production (a vasodilator and inhibitor of platelet aggregation) and increased fetal-placental thromboxane A2 production (a vasoconstrictor). This could result in increased uteroplacental perfusion pressure, maternal hypertension, and increased maternal platelet aggregation. We also suggest that women who develop idiopathic toxemia of pregnancy are at increased risk for adult onset diabetes later on in life because they have a mild derangement in glucose-insulin homeostasis during their reproductive years that results in increased uterine vascular damage, that leads to decreased uterine blood flow, and ultimately the fetal hyperinsulinemia-prostaglandin pressor release mechanism. Therefore, prevention of toxemia may be possible by correction of mild derangements in glucose-insulin receptor homeostasis before conception occurs.
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PMID:Theory of the etiology of human toxemia of pregnancy: fetal hyperinsulinemia as a compensatory response to decreased uterine blood flow. 330 29

The prevalence of non-insulin dependent diabetes mellitus (NIDDM) is higher in Mexican Americans (MAs) than in non-Hispanic whites (NHWs) even after adjustment for the former's greater overall and more centralized adiposity. We previously have shown that MAs are more hyperinsulinemic than NHWs even after adjustment for body mass index (BMI), waist-to-hip ratio (WHR), subscapular-to-triceps skinfold ratio, and glucose tolerance. We now confirm these findings in much larger population (n = 1,182). Since hepatic extraction of insulin may be decreased with upper body adiposity, we also measured fasting and 2-hour C-peptides in a subset of subjects (n = 70). C-peptide concentrations were higher in MAs than in NHWs indicating that MAs have higher insulin secretion. We examined whether the increased insulin concentrations in MAs may be associated with a bimodal distribution of insulin concentrations in which the second or higher mode might represent pre-diabetics. No evidence of bimodality, however, was apparent. The effect of overall adiposity (BMI) and upper body adiposity was similar in both Mexican Americans (a high risk population for NIDDM) and non-Hispanic whites (a low risk population for NIDDM). These data indicate that, like other populations at high risk for NIDDM such as Pima Indians in the U.S. Southwest and Micronesians in the South Pacific, Mexican Americans have more hyperinsulinemia than can be accounted for by their adiposity and body fat distribution. Prolonged insulin secretion (secondary to increased insulin resistance), is one possible explanation for this phenomenon which could lead to islet cells decomposition and eventual clinical diabetes.
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PMID:Hyperinsulinemia as a possible etiology for the high prevalence of non insulin dependent diabetes in Mexican Americans. 330 61

In the longitudinal Schwabing study, unselected insulin-treated diabetic patients were followed for major vascular complication (MVC) (stroke, myocardial infarction, gangrene) and asymptomatic, early detectable peripheral vascular disease (PVD). In the group of insulin-treated NIDDM multiple logistic regression analysis revealed the number of daily injected insulin units as a significant predictor for MVC and PVD (t = 1.98; p less than 0.04; x +/- S.D.: PVD yes 57.6 +/- 21.4 U/d; PVD no 44.3 +/- 17.7; age-adjusted univariate p less than 0.001). Daily insulin dose correlated highly significantly with serum triglycerides (r = 0.40, p less than 0.001) as well as with blood glucose (r = 0.33, p less than 0.001). These data suggest that insulin resistance is characteristic for atherosclerotic disease in NIDDM and the hyperinsulinemia-hypertriglyceridemia-syndrome might be a powerful cardiovascular risk factor in diabetes mellitus.
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PMID:Daily insulin dose as a predictor of macrovascular disease in insulin treated non-insulin-dependent diabetics. 330 65

Hyperinsulinaemia is of great importance, being a primary risk factor for cardiovascular disease and non-insulin dependent diabetes (NIDDM). Furthermore, unwanted effects of increased exposure of tissues to insulin are known. Hyperinsulinaemia may, in principle, be caused by primary hypersecretion, or be a secondary consequence of diminished effectiveness of insulin in the periphery. Obesity is the commonest condition characterized by insulin resistance, which is seen most frequently when excess adipose tissue is localized to the abdominal region. Insulin resistance in obesity is found in several tissues, however, with liver and muscle being quantitative the most important. Muscle insulin sensitivity is regulated by genetic factors, hormonal effects, and the influence of free fatty acids, as well as the state of physical activity. There is evidence for the action of each of these factors in obesity. The pathogenetic mechanisms linking hyperinsulinaemia with cardiovascular disease and NIDDM are unknown. Comparisons between development of NIDDM in experimental animal models and in humans in prospective studies however, provide useful hypotheses for further studies.
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PMID:Adipose tissue distribution, plasma insulin, and cardiovascular disease. 330 69

The relative effects of obesity alone, and in combination with fasting hyperinsulinemia and glucose intolerance, on the peripheral action of insulin in adipose tissue were investigated in twenty-four 60-yr-old men, who had been followed for 10 yr. They were divided into four groups of six subjects each on the basis of the following criteria: (1) normal body weight, normal fasting insulin level, and normal glucose tolerance; (2) moderate obesity, normal fasting insulin level, and normal glucose tolerance; (3) moderate obesity, fasting hyperinsulinemia, and normal glucose tolerance; and (4) moderate obesity, fasting hyperinsulinemia, and newly developed, moderate, untreated fasting hyperglycemia and/or glucose intolerance (i.e., mild type II diabetes mellitus). Specific adipocyte insulin binding and the effects of the hormone on adipose tissue lipolysis and glucose oxidation were determined. Insulin receptor binding per cell and per cell surface area were similar in all four groups. Regarding antilipolysis, the insulin sensitivity was the same in all groups and the maximum effect was significantly increased in the three obese groups, as compared with the normal-weight control group. In groups 1-3, insulin stimulated adipose tissue glucose oxidation in a dose-dependent way, and the sensitivity and responsiveness to insulin were comparable. In contrast, in the obese glucose-intolerant subjects (4) there was no significant effect of insulin on glucose oxidation when the hormone was added in increasing concentrations of less than or equal to 35 nmol/L. The basal glucose oxidation was similar in all four study groups. The in vivo insulin tolerance was gradually reduced in groups 2-4, as compared with the normal-weight control group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of obesity, hyperinsulinemia, and glucose intolerance on insulin action in adipose tissue of sixty-year-old men. 351 39

It has been widely reported that dysfunctions of pancreatic A-cell occur in diabetics. Since these pancreatic A-cell dysfunctions are not normalized by conventional insulin injection treatment, they were thought to be a primary defect of diabetes mellitus. Recently it was found that paradoxic glucagon secretion to oral glucose and excessive glucagon response to i.v. arginine could be perfectly normalized if strict blood glucose regulations were achieved with appropriate insulin treatment. However, there has been no report on the perfect normalization of glucagon secretion in response to insulin-induced hypoglycemia in diabetics. In this report, to elucidate the precise significance of A-cell function in hypoglycemia in diabetics, the effect of long-term strict glycemic regulations and the importance of intact autonomic nerve function on hypoglycemia-induced glucagon secretion were studied. In experiments on hypoglycemia-induced glucagon secretion in diabetics, 0.2 to 0.3 U/kg of regular insulin injection were usually employed to overcome the hyperglycemia and insulin resistance. However, hyperinsulinemia has been demonstrated to suppress A-cell function in experiments using the euglycemic clamp technique. Therefore, the effect of plasma insulin concentrations after insulin injections was first studied in 7 healthy volunteers by injecting insulin at doses of 0.1 U/kg and 0.3 U/kg. In this experiment with 0.3 U/kg of insulin, the rate of fall in glycemia and the nadir of blood glucose were made similar to that with 0.1 U/kg of insulin by using glucose clamp technique with artificial endocrine pancreas. The plasma glucagon response after 0.3 U/kg of insulin was significantly suppressed as compared to that after 0.1 U/kg of insulin. From these experiments, it was concluded that not only hypoglycemic stimuli but also plasma insulin concentrations are important factors for demonstrating significant glucagon secretion in response to insulin-induced hypoglycemia. Second, the effects of strict glycemic control and autonomic nerve function on hypoglycemia-induced glucagon secretion were studied. Regular insulin at a dose of 0.1 U/kg was injected in an i.v. bolus form into 21 insulin-dependent (IDDM) and 22 noninsulin-dependent (NIDDM) diabetics before and one to three months after strict glycemic control with multiple insulin injection therapy or continuous subcutaneous insulin infusion therapy. To reduce fasting blood glucose level and to obtain the same hypoglycemic stimuli, overnight insulin infusion at a basal dose was undertaken in IDDM who showed hyperglycemia before strict glycemic regulations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Mechanism of the blunted glucagon response to insulin-induced hypoglycemia in diabetics]. 354 95

We studied the dose-response characteristics of insulin's ability to modulate its own secretion in normal and type II diabetic (NIDDM) subjects by measuring suppression of serum C-peptide levels during insulin infusions with the plasma glucose level held constant. In normal subjects at euglycemia, primed continuous insulin infusion rates of 15, 40, 120, and 240 mU/M2 X min acutely raised serum insulin to steady state levels of 37 +/- 2 (+/- SE), 96 +/- 6, 286 +/- 17, and 871 +/- 93 microU/ml, respectively. During each infusion, maximal suppression of C-peptide to 30% of basal levels occurred by 130 min. At the higher insulin levels (greater than or equal to 100 microU/ml), C-peptide levels fell rapidly, with an apparent t1/2 of 13 min, which approximates estimates for the t1/2 of circulating C-peptide in man. This is consistent with an immediate 70% inhibition of the basal rate of insulin secretion. At the lower insulin level (37 +/- 2 microU/ml), C-peptide levels fell to 30% of basal values less rapidly (apparent t1/2, 33 min), suggesting that 70% inhibition of basal insulin secretion rates was achieved more slowly. In NIDDM subjects, primed continuous insulin infusion rates of 15, 40, 120, and 1200 mU/M2 X min acutely raised serum insulin to steady state levels of 49 +/- 7, 93 +/- 11,364 +/- 31, and 10,003 +/- 988 microU/ml. During studies at basal hyperglycemia, only minimal C-peptide suppression was found, even at pharmacological insulin levels (10,003 +/- 988 microU/ml). However, if plasma glucose was allowed to fall during the insulin infusions, there was a rapid decrease in serum C-peptide to 30% of basal levels, analogous to that in normal subjects. Three weeks of intensive insulin therapy did not alter C-peptide suppression under conditions of hyperinsulinemia and falling plasma glucose. The following conclusions were reached. 1) In normal subjects, insulin (40-1000 microU/ml) inhibits its own secretion in a dose-responsive manner; more time is required to achieve maximal 70% suppression at the lower insulin level (40 microU/ml). 2) In NIDDM studied at basal hyperglycemia, insulin has minimal ability to suppress its own secretion. Thus, impaired feedback inhibition could contribute to basal hyperinsulinemia. 3) Under conditions of hyperinsulinemia and falling plasma glucose, insulin secretion is rapidly suppressed in NIDDM (analogous to that in normal subjects studied during euglycemia.
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PMID:Modulation of insulin secretion by insulin and glucose in type II diabetes mellitus. 388 36

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