Search Results - (Author, Cooperation:J. M. Olefsky)

2015-03-06

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

2014-07-22

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Animals ; Blood Glucose/metabolism ; Body Weight/drug effects ; Diabetes Mellitus, Experimental/drug therapy/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Diet, High-Fat ; Dose-Response Relationship, Drug ; Fibroblast Growth Factor 1/administration & dosage/adverse effects/*pharmacology ; Glucose/*metabolism ; Glucose Tolerance Test ; Humans ; Insulin/*metabolism ; Insulin Resistance ; Liver/drug effects/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Mitogens/pharmacology ; Muscle, Skeletal/drug effects/metabolism ; Receptor, Fibroblast Growth Factor, Type 1/metabolism

2012-04-24

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Adipocytes/drug effects/metabolism/pathology ; Animals ; Base Sequence ; Cell Size/drug effects ; Diabetes Mellitus, Experimental/chemically induced/genetics/pathology ; Diet, High-Fat/adverse effects ; Fibroblast Growth Factor 1/deficiency/*genetics/*metabolism ; *Homeostasis/drug effects ; Humans ; Inflammation/genetics ; Insulin/metabolism ; Insulin Resistance ; Intra-Abdominal Fat/drug effects/*metabolism/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Necrosis/enzymology ; PPAR gamma/*metabolism ; Promoter Regions, Genetic/genetics ; Response Elements/genetics

1432-0428

Hyperinsulinaemia ; rat adipocytes ; glucose oxidation ; glucose transport ; lipogenesis

Springer Online Journal Archives 1860-2000

Medicine

Summary Glucose oxidation and lipogenesis were studied in isolated adipocytes from control and nonobese, experimentally hyperinsulinaemic rats. In cells from the hyperinsulinaemic animals oxidation of either [1-14C]- or [6-14C] glucose was increased in the presence or absence of insulin, at substrate concentrations from 0.1 to 20 mmol/l. Glucose incorporation into total triglycerides and fatty acids was also increased. These enhanced rates of glucose metabolism were due to increased activity of the glucose transport system in addition to increased activity of intracellular glucose metabolism. Therefore, these data indicate that insulin can influence long term glucose homoeostasis by augmenting the overall cellular capacity for glucose metabolism at several loci.

Electronic Resource

1432-0428

Hypertriglyceridaemia ; insulin resistance ; hyperinsulinaemia ; hepatic glucose output ; triglyceride metabolism

Springer Online Journal Archives 1860-2000

Medicine

Summary Plasma insulin response to oral glucose, insulin resistance, and insulin suppression of hepatic glucose production were studied in 11 normal subjects and 11 hypertriglyceridaemic patients. Patients with hypertriglyceridaemia had a significantly higher insulin response to oral glucose. Insulin resistance was also significantly greater in hypertriglyceridaemic subjects as determined by measuring the steady-state plasma glucose response during a continuous infusion of epinephrine, propranolol, glucose, and exogenous insulin. Insulin suppression of hepatic glucose production was calculated from the results of two studies in which glucose turnover rate was measured by a continuous infusion of3H-2-glucose. The first study was performed under conditions of basal insulin secretion, and the second carried out at steady state exogenous insulin levels of approximately 100 μU/ml. The results indicated that basal hepatic glucose production was the same in both groups, and was suppressed to an equal degree by physiological levels of insulin. These data demonstrate that hepatic glucose production can be suppressed to an equal degree in normal and hypertriglyceridaemic subjects at comparable circulating insulin levels, at the same time that resistance to insulin-stimulated glucose uptake is observed in the hypertriglyceridaemic individuals.

Electronic Resource

1432-0428

Insulin ; adipocytes ; prednisolone ; dexamethasone ; insulin binding ; deoxyglucose transport ; glucose oxidation

Springer Online Journal Archives 1860-2000

Medicine

Summary We have studied the effects of dexamethasone and prednisolone in vitro and in vivo on insulin binding, deoxyglucose uptake and glucose oxidation in rat adipocytes. In the studies in vivo, rats were treated for 22 h with dexamethasone (30 μg/kg) or prednisolone (200 μg/kg). Following sacrifice, adipocytes were prepared and the results demonstrated that cells from prednisolone treated rats showed a 17% increase in insulin binding and increased rates of basal and insulin stimulated deoxyglucose uptake and glucose oxidation. Conversely, dexamethasone administration resulted in a 22% decrease in insulin binding, and decreased rates of deoxyglucose uptake and glucose oxidation by the cells. Thus, prednisolone and dexamethasone had opposite effects in vivo. In contrast to the opposite effects of the two glucocorticoids in vivo, dexamethasone and prednisolone (each at a concentration of 1 μmol/l) had similar effects on adipocytes in vitro. Incubation of adipocytes with the steroids did not alter insulin binding, while both agents led to a comparable decrease in the rates of basal and insulin stimulated deoxyglucose uptake and glucose oxidation. Thus, dexamethasone and prednisolone have opposite effects on adipocyte glucose metabolism in vivo but have similar effects in vitro.

Electronic Resource

1432-0428

Insulin resistance ; diabetes ; glucagon ; insulin ; glucagon secretion

Springer Online Journal Archives 1860-2000

Medicine

Summary Using a constant intravenous infusion technique we have measured in vivo insulin resistance in 17 normal subjects, five patients with chemical diabetes, and 13 non-ketotic diabetic patients with fasting hyperglycaemia (FBS〉120 mg/ 100 ml). All of the diabetic patients were non-obese. The results demonstrated that the diabetic patients were insulin resistant compared to normals and that the degree of insulin resistance was greater the more severe the diabetes. No differences in plasma glucagon levels were found among the different groups during the infusion studies. These results demonstrate that non-obese, non-ketotic diabetic patients are insulin resistant and that abnormalities in plasma glucagon concentrations do not account for this insulin resistance.

Electronic Resource

1432-0428

Insulin resistance ; insulin response ; maturity onset diabetes ; Aetiology of diabetes ; Heterogeneity of diabetes

Springer Online Journal Archives 1860-2000

Medicine

Summary Plasma insulin responses and insulin resistance were determined in 75 subjects, defined as having a normal, borderline abnormal, or abnormal oral glucose tolerance test (OGTT). Although considerable heterogeneity of insulin response existed, most patients with abnormal OGTT's had insulin responses greater than normal; none had insulin responses less than normal. The degree of insulin resistance also varied, but most patients with abnormal OGTT's were also abnormally insulin resistant. A significant correlation (r=0.64, p ±0.001) existed between insulin response and the degree of insulin resistance. However, when both variables were taken into consideration, the entire population could be divided into two groups. One group was characterized by both normal insulin responsiveness and sensitivity, the other by increased insulin response, associated with greater insulin resistance. Most patients with abnormal OGTT's fell into the latter group, but some had glucose intolerance without either an exaggerated insulin response or insulin resistance. These results suggest that true heterogeneity exists in patients with abnormal OGTT's.

Electronic Resource

1432-0827

Islet amyloid polypeptide ; Amylin ; Calcium ; Urine ; Parathyroid hormone

Springer Online Journal Archives 1860-2000

Biology

Medicine

Physics

Abstract Islet amyloid polypeptide (IAPP) is a member of the calcitonin/CGRP family and has been isolated from the β-cell of pancreatic islets. Recent evidence suggests that this peptide may be involved in calcium metabolism in that its administration resulted in lowering of serum calcium levels. To determine the mechanism of IAPP-induced hypocalcemia, the peptide was infused at 50 pmol/min/kg for 90 minutes in conscious male mongrel dogs. Infusion of the peptide resulted in a modest decline in the total serum calcium concentration (10.4±0.2 to 9.4±0.2 mg/dl; P〈0.05) and a concomitant increase in urinary calcium excretion (3.6±0.6 to 6.9±2.0 mg/dl; P〈0.01). Based on an extracellular volume of 7 liter in a 28 kg dog, the total decrement in calcium due to IAPP was 41.3±2.4 mg, whereas the total increase in urinary calcium was 3.2±0.7 mg. There were no detectable changes in calcitonin. We conclude that IAPP lowers serum calcium and increases the renal excretion of calcium independently of calcitonin. However, the calciuria can only account for a small component of the hypocalcemic effect and therefore, an additional calcium lowering effect of IAPP exits.

Electronic Resource

1573-4919

Springer Online Journal Archives 1860-2000

Biology

Chemistry and Pharmacology

Medicine

Summary We have examined some of the chemical and biological characteristics of the insulin-derived cell-associated radioactivity following incubation of isolated adipocytes with 125I-insulin (10−10 M) for one hour at 37 °C S ephadex G-50 chromatography of the cell-associated radioactivity demonstrated three peaks: peak I eluted with the void volume and consisted of large molecular weight material; peak II comigrated with 1251-insulin; and peak III consisted of small molecular weight degradation products (probably iodotyrosine). When the insulin peak (peak II) was divided into fourths, it was found that the binding and biologic activity of this material was not homogenous; thus, binding and biologic activity (relative to native insulin) fell markedly from the earliest to the latest eluting fractions of this peak. Furthermore, when the entire peak 11 material was applied to DEAE-Sephacel and eluted with a 0.01–0.2 M NaCl gradient, three distinct peaks were observed. These peaks were all 90% TCA precipitable, whereas the ability of the latter two eluting peaks to precipitate with anti-insulin antiserum was markedly reduced. When similar experiments were performed with chloroquine-treated cells, a large increase in cell-associated radioactivity was observed, and Sephadex G-50 chromatography demonstrated that this increase was entirely confined to peaks I and II. When the insulin peak (peak II) was divided into fourths, it was found that chloroquine markedly inhibited the decreased binding and biologic activity, from the earliest to the latest eluting fraction of this peak. Furthermore, when the peak II material (Sephadex G-50) from chloroquine-treated cells was chromatographed on DEAE-Sephacel, this material eluted in a single peak which was 95% TCA precipitable and 106% precipitable by anti-insulin antiserum. In conclusion, these studies demonstrate that: 1) intermediate insulin-derived products with reduced binding and biologic activity are generated in the process of cellular insulin degradation, and 2) the formation of these intermediate products is mediated by a chloroquine-sensitive pathway.

Electronic Resource