Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the dose-response characteristics of impaired glucose oxidation in non-insulin-dependent diabetes mellitus (NIDDM), indirect calorimetry was performed on eight matched control and NIDDM subjects during the basal state and during three glucose clamps at insulin infusion rates of 150, 300, and 1,500 pmol.m-2.min-1. Hyperglycemia was used to achieve matched rates of glucose uptake at each insulin infusion. Glucose uptake in the basal state was greater in NIDDM [3.75 +/- 0.23 vs. 2.50 +/- 0.10 mg.kg fat-free mass (FFM)-1.min-1, P less than 0.005] but was similar at approximately 8, 12, and 26 mg.kg FFM-1.min-1 at each insulin infusion. Basal protein oxidation, fat oxidation, and plasma free fatty acids were similar and equally sensitive to suppression by insulin in both groups. Glucose oxidation was reduced 20-26%, and circulating lactate increased 50-90% at physiological but not at pharmacological insulin concentrations in NIDDM. The dose-response relationship between serum insulin and glucose oxidation was right shifted in NIDDM with half-maximal activation at 368 +/- 91 vs. 179 +/- 27 pM in controls (P less than 0.05). In conclusion, glucose oxidation is reduced at physiological insulin concentrations in NIDDM and cannot be explained by concomitant obesity, increased fat oxidation, or reduced glucose uptake but results from impaired sensitivity to stimulation by insulin, possibly at pyruvate dehydrogenase.
 ...
PMID:Dose-response characteristics of impaired glucose oxidation in non-insulin-dependent diabetes mellitus. 185 69

To study the cross-generation effect of enhanced growth in macrosomic newborn rats, we induced mild hyperglycemia in 15 pregnant Sprague Dawley rats by intraperitoneal injection of streptozotocin, 35 mg/kg body weight, on the 5th d of gestation. As reported previously, we produced hyperinsulinemia and accelerated growth in the fetuses of hyperglycemic dams. We also showed that the macrosomic female pups (second generation) continued to have a higher growth rate through the first 12 wk of life. In this study, the second-generation female rats were mated with macrosomic second-generation males; they demonstrated glucose intolerance during late pregnancy and delivered pups (third generation) with higher birth weight and plasma insulin levels than the pups from control second-generation rats. When the macrosomic third-generation pups were raised under identical nutritional and environmental conditions as controls, the macrosomic rats showed accelerated growth and higher fat tissue weight during the first 12 wk of life. Furthermore, the macrosomia was associated with glucose intolerance and higher insulin to glucose ratios compared to controls. We also mated the offspring of second-generation streptozotocin-injected nonmacrosomic as well as the offspring of macrosomic pups of buffer-injected dams; none of the pups from these matings were significantly macrosomic. Therefore, we conclude that the perpetuation of obesity and possibly glucose intolerance across generations in this rat model is predominantly a result of abnormal intrauterine metabolic environment rather than genetic factor driven.
 ...
PMID:The cross-generation effect of neonatal macrosomia in rat pups of streptozotocin-induced diabetes. 186 17

The risk of developing macroangiopathy associated with diabetes led us to study in sand rats the long-term consequences of non-insulin-dependent diabetes on the development of arterial lesions promoted by feeding a high-cholesterol diet. Gliclazide, an agent whose preventive effect has previously been suggested in other experimental models of atheroma, was also investigated in these diabetic and hypercholesterolemic animals. Sand rats were fed a natural diet (ND group), a standard laboratory feed (StD group), or a high-cholesterol feed (HCD group) for 15 months. Biologic parameters were monitored throughout the period of the study, and histologic and histochemical examinations were conducted when the animals were killed (month 15). One StD group and one HCD group were treated with gliclazide from month 3 to month 15. The StD group developed a syndrome of obesity, hyperglycemia, hyperinsulinemia, and triglyceridemia. The high cholesterol feed further increased hypercholesterolemia. These biologic abnormalities were accompanied by arterial lesions (thickening of the intima, deposition of glycosaminoglycans). Foam cells were seen in the intima, and microthrombi were present in the lumen of the arteries of animals in the HCD group. Long-term gliclazide medication at doses that normalized serum glucose levels also reduced the obesity, hyperinsulinemia, lipid disorders, and it prevented or retarded the appearance of arterial lesions.
 ...
PMID:Development of macroangiopathy in sand rats (Psammomys obesus), an animal model of non-insulin-dependent diabetes mellitus: effect of gliclazide. 187 6

In C3H mice, a major component of susceptibility to the diabetogenic action of an obesity mutation (diabetes, db) is male gender associated. We tested whether increased male susceptibility was an androgen receptor mediated process. C3H.SW/Lt-derived db/db males were rendered androgen-receptor function-deficient by introducing the testicular feminization (Tfm) mutation of the X-linked androgen receptor gene. The db/db Tfm/Y males (phenotypically female in appearance) developed severe diabetes indistinguishable from that observed in standard db/db X + Y males. Castration of standard C3H.SW/Lt-db/db males (producing mutants with normal androgen receptors but reduced serum testosterone) also failed to block the gender-enhanced susceptibility. In contrast, female db/db littermates exhibited a milder hyperglycemia, and were more resistant to pancreatic beta cell necrosis and islet atrophy than any of the groups of db/db males. Although these data indicated that male-enhanced sensitivity to diabetogenic stress was independent of circulating androgens, the possibility that the gender dimorphism is predicated upon tissue ratios of active estrogens to androgens in glucose-producing tissues such as liver is discussed.
 ...
PMID:Effect of androgen insensitivity on diabetogenesis in db/db male mice with testicular feminization (Tfm). 187 72

The effect of long-term (12 weeks) oral treatment with sodium orthovanadate on hepatic glycogen metabolizing and lipogenic enzymes was studied in genetically diabetic db/db mice. These mice were characterized by significant (P less than .001) obesity, hyperglycemia, and hyperinsulinemia. Vanadate administration led to significant decreases in body weight (P less than .001) and plasma insulin levels (P less than .01) and the mice became normoglycemic. The total glycogen synthase (EC 2.4.1.11) activity in the livers of diabetic mice showed a 47% increase, which did not undergo any significant change after treatment with vanadate. Hepatic phosphorylase (EC 2.4.1.1) activities (a and total) showed twofold increases in db/db mice when compared with the nondiabetic ones. Vanadate caused significant decreases in phosphorylase a (P less than .02) and total phosphorylase (P less than .001) activities. Glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and malic enzyme (EC 1.1.1.40) in diabetic liver had differential alterations, as indicated by a 50% decrease in glucose-6-phosphate dehydrogenase and 160% increase in malic enzyme activities. Vanadate administration led to normalization of both enzyme activities. In nondiabetic mice, vanadate treatment did not cause changes in any parameter, except for a 46% decrease in plasma insulin levels. This investigation indicates that vanadate can normalize many of the metabolic abnormalities seen in the liver of genetically diabetic db/db mice, a model for non-insulin-dependent diabetes mellitus (NIDDM). Vanadate also causes a decrease in plasma insulin level, along with normalization of plasma glucose, which suggests a partial reversal of insulin resistance.
 ...
PMID:Long-term effects of vanadate treatment on glycogen metabolizing and lipogenic enzymes of liver in genetically diabetic (db/db) mice. 191 Jan 43

It is known that obese subjects have a blunted GH secretory response to stimulation, but little is known about the inhibition of GH secretion in obesity. The present study was designed to evaluate the effects of obesity on the suppression of GH by hyperglycemia and/or somatostatin. Plasma GH concentrations were measured in eight nondiabetic obese subjects and eight nonobese healthy controls during a 4-h hyperglycemic clamp. During the third hour synthetic cyclic somatostatin-14 was infused at the rate of 2.5 nmol/min. Baseline plasma GH levels were similar in obese and nonobese subjects (0.9 +/- 0.1 vs. 0.8 +/- 0.2 micrograms/L; mean +/- SEM). In the last 20 min of the glucose infusion period preceding somatostatin administration (100-120 min of the study) plasma GH averaged 0.8 +/- 0.1 micrograms/L in obese patients and 0.4 +/- 0.1 micrograms/L in control subjects (P less than 0.01), with a reduction of 6 +/- 5% in the former and 35 +/- 10% in the latter (P less than 0.01). In both groups somatostatin infusion did not result in a further decrease in plasma GH. Discontinuation of the somatostatin infusion resulted in a rise in both groups; the increase was higher in nonobese subjects (8.1 +/- 3.8 vs. 2.3 +/- 0.9 micrograms/L in the period 220-240 min; P = NS). These results suggest that in human obesity, hyperglycemia has a diminished inhibitory effect on GH secretion, and somatostatin administration has no additional effect in either obese or nonobese nondiabetic subjects.
 ...
PMID:Plasma concentrations of growth hormone during hyperglycemic clamp with or without somatostatin infusion in obese subjects. 197 27

In the present study we evaluated the regulation of plasma free fatty acid (FFA) concentration by glucose and insulin in human obesity. To this purpose we measured plasma FFA concentration in normoglycemic, normoinsulinemic obese (n = 8) and nonobese (n = 8) healthy subjects during 240 min of exogenous hyperglycemia (hyperglycemic glucose clamp) in presence of both glucose-stimulated (0-120 min and 180-240 min) and somatostatin-inhibited (120-180 min) insulin secretion. We found that plasma FFA curves were roughly parallel in the 0-120 min period and FFA values of obese subjects were constantly higher throughout the experimental period. Moreover, the difference between the two groups was significant when individual data were expressed as a percent of fasting FFA value (P less than 0.0001 from 0 to 120 min). Plasma insulin levels were similar in the two groups during the entire study. The amount of glucose metabolized during the 80-120 min period was significantly lower in obese than in nonobese subjects (172 +/- 7 v. 341 +/- 11 mg/m2.min, P less than 0.01; means +/- s.e.). During the somatostatin period (120-180 min) plasma insulin was lowered close to basal values in both groups (116 +/- 15 and 109 +/- 11 pmol/l) and plasma FFA concentrations rose in a linear fashion. Our data suggest that suppression of plasma FFA concentrations by glucose and insulin is qualitatively similar in healthy nonobese and obese subjects, the latter having higher FFA values. Insulin action on FFA metabolism isn ot grossly impaired in obese subjects who are clearly insulin resistant as far as glucose metabolism is concerned.
 ...
PMID:Plasma free fatty acid concentration during hyperglycemic glucose clamp with and without somatostatin infusion in obese subjects with normal glucose tolerance. 197 21

The aim of the present study was to evaluate whether the inhibitory effect on pancreatic A-cell exerted by hyperglycemic hyperinsulinemia and/or by somatostatin administration is impaired in human obesity. For this purpose plasma glucagon concentrations were measured in 8 obese and 8 nonobese nondiabetic subjects during a 4-h hyperglycemic clamp. Synthetic cyclic somatostatin-14 was infused at the rate of 2.5 nmol/min during the third hour of the study. Fasting plasma glucagon was higher in obese than in nonobese subjects (242 +/- 32 vs 163 +/- 15 pg/ml, p less than 0.05) (mean +/- SEM). In the last 20 min of the glucose infusion period preceding somatostatin administration (100-120 min of the study) plasma glucagon averaged 195 +/- 26 pg/ml in obese and 122 +/- 13 pg/ml in nonobese subjects (p less than 0.05), with a reduction of 19 +/- 3% in the former and 28 +/- 4% in the latter (p = n.s.). In both groups somatostatin infusion did not result in a further decrease in plasma glucagon, which averaged 192 +/- 27 pg/ml in obese and 123 +/- 16 pg/ml in nonobese subjects (p less than 0.05) in the 160-180 min period of the study. Also after discontinuing somatostatin infusion plasma glucagon levels did not change. These results suggest that in human obesity hyperglycemic hyperinsulinemia has a normal inhibitory effect on pancreatic A-cell and that somatostatin administration has no additive effect on hyperglycemia and hyperinsulinemia in either obese or nonobese nondiabetic subjects.
 ...
PMID:Plasma concentrations of glucagon during hyperglycemic clamp with or without somatostatin infusion in obese subjects. 198 86

In 1960, immunoassays of insulin first demonstrated significant quantities of circulating hormone in non-insulin-dependent (type II) diabetes and for 30 yr have fostered debate as to whether a beta-cell abnormality plays an etiological role in this syndrome. Early efforts to determine the adequacy of islet beta-cell function showed that obesity and its associated insulin resistance were major confounding variables. Subsequently, it was recognized that glucose not only directly regulated insulin synthesis and secretion but moderated all other islet signals, including other substrates, hormones, and neural factors. When both obesity and glucose are taken into account, it becomes clear that patients with fasting hyperglycemia all have abnormal islet function. Type II diabetes is characterized by a defect in first-phase or acute glucose-induced insulin secretion and a deficiency in the ability of glucose to potentiate other islet nonglucose beta-cell secretagogues. The resulting hyperglycemia compensates for the defective glucose potentiation and maintains nearly normal basal insulin levels and insulin responses to nonglucose secretagogues but does not correct the defect in first-phase glucose-induced insulin release. Before the development of fasting hyperglycemia, only first-phase glucose-induced insulin secretion is obviously defective. This is because progressive islet failure is matched by rising glucose levels to maintain basal and second-phase insulin output. The relationship between islet function and fasting plasma glucose is steeply curvilinear, so that there is a 75% loss of beta-cell function by the time the diagnostic level of 140 mg/dl is exceeded. This new steady state is characterized by glucose overproduction and inefficient utilization. Insulin resistance is also present in most patients and contributes to the hyperglycemia by augmenting the glucose levels needed for compensation. Decompensation and absolute hypoinsulinemia occur when the renal threshold for glucose is exceeded and prevents further elevation of circulating glucose. The etiology of the islet beta-cell lesion is not known, but a hypothesis based on basal hyperproinsulinemia and islet amyloid deposits in the pancreas of type II diabetes is reviewed. The recent discovery of the islet amyloid polypeptide (IAPP) or amylin, which is the major constituent of islet amyloid deposits, is integrated into this hypothesis. It is suggested that pro-IAPP and proinsulin processing and mature peptide secretion normally occur together and that abnormal processing, secondary to or in conjunction with defects in hormone secretion, lead to progressive accumulation of intracellular IAPP and pro-IAPP, which in cats, monkeys, and humans form intracellular fibrils and amyloid deposits with a loss of beta-cell mass.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Banting lecture 1990. Beta-cells in type II diabetes mellitus. 199 68

Decreased glucose-induced thermogenesis has been observed in all forms of obesity. However, some studies implicate insulin resistance rather than obesity per se as the mechanism by which glucose-induced thermogenesis is reduced. To establish the role of insulin resistance in reduced thermogenesis independent of obesity, we compared energy expenditure in 9 nonobese individuals with noninsulin-dependent diabetes mellitus (NIDDM) to 16 nonobese control subjects using indirect calorimetry and the hyperinsulinemic clamp technique. To document the presence of insulin resistance and reduced glucose-induced thermogenesis in nonobese NIDDM, 6 individuals from each group were studied under identical conditions of hyperinsulinemia (120 mU/m2.min) and euglycemia (approximately 5 mmol/l). Both glucose uptake (0.482 +/- 0.042 vs. 0.737 +/- 0.040 g/min) and energy expenditure above basal (0.04 +/- 0.02 vs. 0.10 +/- 0.02 kcal/min) were decreased in nonobese NIDDM compared to control subjects (both P less than 0.05). To determine whether decreased glucose-induced thermogenesis could be overcome by correcting for reduced glucose uptake, the 9 nonobese NIDDM individuals were age and weight-matched to 9 control subjects and clamps were performed at matched rates of glucose uptake. During a 40 mU/m2.min insulin infusion, the nonobese NIDDM individuals were studied at hyperglycemia (17.5 +/- 1.9 mmol/L) and compared to the control subjects at euglycemia (5.1 +/- 0.1 mmol/L; P less than 0.05). Under these conditions, both groups achieved similar rates of glucose uptake (0.698 +/- 0.040 vs. 0.688 +/- 0.038 g/min, NIDDM and control subjects, respectively) and similar rates of energy expenditure above basal (0.08 +/- 0.03 vs. 0.06 +/- 0.02 kcal/min, P = NS). During 600 mU/m2.min clamps performed at hyperglycemia (19.0 +/- 1.2 vs. 14.5 +/- 1.1 mmol/L, NIDDM vs. control subjects, respectively; P less than 0.05), rates of maximal glucose uptake (1.538 +/- 0.093 vs. 1.518 +/- 0.047 g/min) and energy expenditure above basal (0.34 +/- 0.03 vs. 0.31 +/- 0.03 kcal/min) were also similar (P = NS). In conclusion nonobese NIDDM is associated with both decreased rates of glucose uptake and decreased glucose-induced thermogenesis. Decreased glucose substrate availability, due to impaired insulin action, appears to be the critical determinant of glucose-induced thermogenesis in nonobese NIDDM. These data indicate that decreased thermogenesis in NIDDM is a consequence of insulin resistance and can occur independent of obesity.
 ...
PMID:Reduced glucose-induced thermogenesis is present in noninsulin-dependent diabetes mellitus without obesity. 200 4


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