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Biomedical subjects

M Kasuga

Publications and source records attributed to M Kasuga.

At least 397 records · Page 22Linked to original sources
PubMed1980

Effect of a high glucose diet on insulin binding and insulin action in rat adipocytes. A longitudinal study.

To elucidate the mechanisms whereby changes in dietary composition affect the action of insulin on glucose metabolism, insulin binding and glucose uptake and oxidation have been studied in epididymal fat pad adipocytes from rats fed high glucose diets for 5 and 10 days. After 5 days, insulin binding was increased, the mainly to an increased number of receptors (3.4 X 10(5) vs. 2.4 X 10(5) sites per cell) in spite of increased plasma insulin levels (3.0 +/- 0.2 vs. 2.1 +/- 0.1 microgram/l; P < 0.05). The maximal response of glucose oxidation to insulin was increased (925 +/- 55 vs. 510 +/- 58 n moles/2 X 10(5) cells/2h; P < 0.01) and the dose-response curve of glucose uptake was shifted to the left. After 10 days, receptor number decreased to the control level and the effect of insulin on glucose uptake and oxidation (% basal) were similar to controls. Thus, in the early stage of high glucose feeding, insulin receptor number, and insulin sensitivity of glucose uptake, and insulin responsiveness of glucose oxidation were increased.

Adipose Tissue↗
PubMed1980

Effects of neuraminidase treatment on solubilized insulin receptor.

Neuraminidase treatment of triton-solubilized insulin receptors from rat fat cell membranes caused release of sialic acid and changed the isoelectric point (pI) of the insulin receptor from 4.7 to 5.6. Neuraminidase had no effect on the number or affinity of insulin receptors. These results indicate that the insulin receptor contains sialic acid, but that this sialic acid is not involved in the binding reaction.

Adipose Tissue↗
PubMed1980

HLA-DRw3 in juvenile onset diabetes mellitus in Chinese.

Thirty-nine juvenile onset diabetes mellitus (JOD) patients and 57 healthy Chinese were HLA-typed in Taiwan. The incidence of HLA-DRw3 was significantly increased in patients when compared with the control group (R.R. = 5.8, P = 0.0027). The frequencies of HLA-B17, which showed linkage disequilibrium with DRw3, and Bw54 were increased in patients, but these increases were not significant because of the small number tested. The DR antigen associated with JOD was the same among Chinese and Caucasians, which suggested that at least one of the susceptibility genes to JOD would be commonly in linkage disequilibrium with DRw3 in the two populations.

Adult↗
PubMed1980

Insulin receptor function and insulin effects on glucose metabolism in adipocytes from ventromedial hypothalamus-lesioned rats.

To investigate the mechanism of the development of insulin resistance in hypothalamic obesity, we studied insulin binding, glucose transport, and glucose oxidation in adipocytes from ventromedial hypothalamus (VMH)-lesioned rats 1 and 2 weeks after injury. One week after injury, insulin binding and insulin-stimulated glucose oxidation were increased, but insulin-stimulated glucose transport was similar to control. Two weeks after injury, insulin binding and insulin-stimulated glucose transport were similar to control, but insulin-stimulated glucose oxidation was decreased. Thus, cellular insulin responsiveness was increased in adipocytes from VMH-lesioned rats 1 week after injury; this increase in insulin responsiveness was due mainly to the increased intracellular glucose metabolism. On the other hand, cellular insulin resistance existed in adipocytes from VMH-lesioned rats 2 weeks after injury; this insulin resistance was also due mainly to a defect in intracellular glucose metabolism.

Adipose Tissue↗
PubMed1979

Solubilization of insulin binding and degrading activity from guinea pig kidneys.

Insulin binding and degrading activities were solubilized by a nonionic detergent. Triton X-100, from guinea pig kidney particulate fractions (100,000 x g pellet). The solubilized insulin binding activity appeared as a single peak on Sepharose 6B gel filtration with a Stokes radius of 73 A. The pI of the solubilized insulin binding activity determined by flat-bed isoelectric focusing was 5.6. On the other hand, the Stokes radius of the solubilized moelcule with insulin degrading activity was 54 A by the same column with a pI of 5.2. More than 98% of the insulin binding activity could be adsorbed to a column of concanavalin A-agarose, while about 94% of the insulin degrading activity could not be adsorbed to this column. These results strongly suggest that the macromolecule for the insulin binding activity is not identical to that for the insulin degrading activity.

Animals↗
PubMed1978

Congenital generalized lipodystrophy with insulin-resistant diabetes.

Hyperglycemia, glucose intolerance, hyperinsulinemia and resistance to exogenous insulin were found in a 10-year-old Japanese boy diagnosed as having congenital generalized lipodystrophy. Studies on insulin receptors of circulating mononuclear leucocytes indicated that insulin-resistant diabetes combined with congenital generalized lipodystrophy may be due to disturbance of insulin binding to membrane receptors. No insulin-binding antibody or antibody that impairs insulin-receptor binding was found. Plasma glucagon showed an exaggerated response to L-arginine before treatment. After treatment with a controlled diet and an oral sulfonylurea (500 mg/day) for 4 weeks, there was improvement in the plasma glucagon response to L-arginine. Improvement in the hyperglycemia, hyperinsulinemia and acanthosis nigricans was also observed. On the other hand, on completion of a 7-day high-fat diet, a marked increase in serum free fatty acids, triglycerides and beta-lipoproteins was observed. The total plasma post-heparin lipolytic activity during the high fat diet was within the normal range. However, the level of protamine-inactivated activity was 3 times that of the control.

Acanthosis Nigricans↗
PubMed1978

Insulin binding and glucose metabolism in adipocytes of streptozotocin-diabetic rats.

To investigate the mechanism of the cellular insulin insensitivity of diabetic rats, insulin binding, glucose transport, and glucose oxidation were studied in adipocytes from streptozotocin-diabetic rats. Increased insulin binding was found in cells from diabetic rats, and this was due to an increased number of insulin receptors rather than a change in receptor affinity. Basal and insulin-stimulated glucose oxidation was decreased in adipocytes from diabetic rats when the data are expressed in absolute terms or as percent increased above basal. Although the absolute rate of basal and insulin-stimulated glucose transport was decreased in adipocytes from diabetic rats, the percent increase above basal of insulin-stimulated glucose transport was not decreased. In conclusion, although the cellular insulin insensitivity exists in adipocytes from diabetic rats, the number of insulin receptors was increased, coupling between insulin receptors and the glucose transport system is intact in adipocytes from diabetic rats, and a defect in intracellular glucose metabolism rather than glucose transport plays a major role in the insulin insensitivity of adipocytes from diabetic rats.

Adipose Tissue↗
PubMed1978

Effects of antiinsulin receptor autoantibody on the metabolism of rat adipocytes.

We have studied the effects of the serum from a patient with an unusual form of diabetic syndrome with extreme insulin resistance on the metabolism of rat adipocytes in vitro. This serum and IgG fractions from it inhibited the [125I]insulin binding to isolated adipocytes and stimulated the 2-deoxyglucose uptake, glucose oxidation, and the incorporation of amino acids into protein. In addition, these fractions inhibited the lipolysis induced by beta 1-24 ACTH in isolated adipocytes. The insulin-like effects of this serum and the effects of insulin were not additive at their maximal concentrations. The inhibition of [125I]insulin binding was due to a decrease in receptor affinity rather than to a change in receptor number by Scatchard plot analysis. Both the inhibition of insulin binding and the insulin-like effects on rat adipocytes were neutralized by antihuman IgG. In addition, these insulin-like effects were abolished by trypsin treatment of adipocytes. These facts suggest that this serum has a circulating antibody directed at or near the insulin receptor itself and that this antibody mimics the insulin effect on rat adipocytes by binding to the insulin receptor in vitro.

Adipose Tissue↗
PubMed1978

Effects of anti-insulin receptor autoantibodies on the metabolism of human adipocytes.

We studied the effect of sera from two patients who had an unusual form of diabetic syndrome with extreme insulin resistance on the metabolism of human adipocytes in vitro. The IgG fractions from sera A and B, which were obtained from two patients (1 and 2) with insulin-resistant diabetes, inhibited [125I] insulin binding to human adipocytes and, at the same time, stimulated glucose oxidation and inhibited the lipolysis induced by levarterenol in human adipocytes. On the other hand, the IgG fraction from the C serum, which was obtained from patient 2 after her diabetic syndrome had completely disappeared as a result of immunosuppressive therapy, did not inhibit [125I] insulin binding to human adipocytes, stimulate glucose oxidation, or inhibit lipolysis in human adipocytes. These facts suggest that these IgG fractions bind to or near the insulin receptor of human adipocytes, that they exhibit their insulin-like effect by binding to the insulin receptor in vitro, and, furthermore, that they are responsible for the extremely insulin-resistant diabetes. However, the apparent discrepancy between the effects of these IgG fractions on man in vitro and in vivo is puzzling and needs to be explained.

Adipose Tissue↗
PubMed1977

Effects of fasting and refeeding of insulin receptors and glucose metabolism in rat adipocytes.

To investigate the mechanism of insulin insensitivity during fasting and hyperresponsiveness to insulin after refeeding, insulin binding, 2-deoxyglucose uptake and glucose oxidation were measured in adipocytes from three groups of rats: control, 48 h fasted, and 48 h refed after 48 h fasting. In 48 h fasted rats, fat cell diameters were decreased to five-sixths of that of the controls and plasma insulin levels were decrease to less than half of the controls; however, after 48 h refeeding, these parameters were restored to normal. In adipocytes from fasted rats, insulin binding was increased but insulin-stimulated 2-deoxyglucose uptake glucose oxidation were significantly decreased as compared to that of the controls. In adipocytes of refed rats, insulin bindings was slightly increased as compared to the controls, accompanied by a slightly decreased 2-deoxyglucose uptake and completely restored glucose oxidation. Conclusions from these studies are that both disorders in coupling of insulin-receptor complexes to glucose transport systems and intracellular glucose metabolism play major roles in the insulin insensitivity of adipocytes from fasted rats, whereas, in adipocytes from refed rats, intracellular glucose metabolism, rather than glucose transport, is mainly involved in restoring insulin sensitivity.

Adipose Tissue↗