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Biomedical subjects

F Ishibashi

Publications and source records attributed to F Ishibashi.

72 records · Page 4Linked to original sources
PubMed1981

Effect of pH and 3-hydroxybutyrate on insulin binding and action in cultured human fibroblasts.

The influence of pH and 3-hydroxybutyrate on insulin binding and action has been studied in cultured human fibroblasts. When the pH of the incubation medium was decreased from 7.6 to 6.8, insulin stimulation of glycogen synthase and total glucose uptake was decreased. The decreased pH induced both an increase in the insulin concentration for half-maximal response, and a decrease in maximal responsiveness. When insulin binding was measured at lower pH, receptor affinity was decreased. The effect of 3-hydroxybutyrate on insulin binding and action was assessed at pH 7.4 and 6.9. In the presence of 3-hydroxybutyrate, insulin binding increased, but insulin action on glycogen synthase and total glucose uptake was unaffected. The data show that insulin action is impaired at lower pH. The decreased sensitivity is probably related to the decrease in insulin binding affinity at lower pH, but decreased maximal responsiveness implies that postreceptor components are also affected by lower pH. The results also suggest that 3-hydroxybutyrate induced a dissociation between binding and response, since an increase of insulin binding was not accompanied by changes in the regulation of glycogen synthase and total glucose uptake.

3-Hydroxybutyric Acid↗
PubMed1981

Type II diabetes and insulin resistance. Evidence of lack of inherent cellular defects in insulin sensitivity.

To determine if inherent cellular differences in insulin sensitivity account for the insulin resistance of non-insulin-dependent diabetes, the effect of insulin on several aspects of cell glucose metabolism was compared in fibroblasts from diabetics and matched nondiabetic controls. The response of total cell glucose metabolism to insulin was assessed by measurement of 14C-glucose uptake. Insulin stimulated cell glucose incorporation in nondiabetic cells up to twofold with half-maximal stimulation at approximately 3 X 10(-9) M insulin. This was similar to that observed in diabetic cells. Insulin stimulation of I glycogen synthase activity was also compared in the cells from diabetics and nondiabetics. Both groups demonstrated a threefold increase in %I activity in the presence of insulin with half-maximal stimulation at approximately 2 X 10(-9) M. There were no differences between diabetics and nondiabetics in either magnitude of response or insulin concentration for half-maximal stimulation. Finally, insulin stimulation of hexose transport was compared in the two cell types using 2-deoxyglucose. In both groups hexose transport was elevated approximately 40% over baseline in the fibroblast in the presence of insulin, with half-maximal stimulation at approximately 2 X 10(-9) M insulin. No differences were found in insulin action on glucose metabolism in fibroblasts form diabetics and nondiabetics; these results may indicate that there are no inherent differences in cell sensitivity to insulin's glucoregulatory action in non-insulin-dependent diabetics.

Adult↗
PubMed1980

Metabolism, 45Ca uptake and insulin releasing capacities of glucose and mannose.

A detailed dose-response study relating mannose and glucose oxidation with the induction of 45Ca uptake and insulin release was performed using in vitro incubation of collagenase digested rat islets of Langerhans. The threshold value for 14C-U-D-glucose oxidation, glucose-stimulation of 45Ca uptake, and insulin release was about 5.5 mM. The half maximal response for these 3 parameters occurred at 13.4 mM, 11.6 mM, and 12.2 mM, respectively. Their maximal responses were obtained at approximately 20 mM. The threshold level for mannose oxidation, induction of 45Ca uptake and insulin release was about 11.0 mM, with half maximal responses obtained at 24.6 mM, 20.5 mM, and 22.2 mM, respectively. The maximum response of the 3 parameters to mannose was obtained at 38.8 mM and appeared to reach the same level obtained for glucose. These results suggest that hexose degradation has a significant role in controlling Ca uptake and subsequent insulin release. A lower rate of mannose oxidation appeared to account for its weaker stimulating efficacy for Ca uptake and insulin release.

Animals↗
PubMed1979

Alloxan inhibits glucose oxidation in the pancreatic islets.

The effects of alloxan on glucose oxidation and the protection by anomers of D-glucose from alloxan inhibition of glucose oxidation in the pancreatic islets were investigated using in vitro incubation of rat isolated islets. The pretreatment by alloxan (5-30 mg/dl) for 6 minutes inhibits significantly 14CO2 formation from 14C-U-D-glucose (10 mM) and the addition of alpha-anomer of D-glucose (8.3 mM) to alloxan (20 mg/dl) completely reverses alloxan inhibition of glucose oxidation. These findings seem to be incompatible with the recent view that alloxan acts at the glucose receptor on the plasma membrane of pancreatic beta-cells without affecting glucose metabolism in the pancreatic islets.

Alloxan↗
PubMed1979

Effect of somatostatin on glucose-induced 45Ca uptake in the pancreatic islets.

This study was designed in an attempt to elucidate a mechanism of somatostatin inhibition of glucose-induced Ca+ uptake by rat pancreatic islets. Rat pancreatic islets were perifused with Krebs-Ringer bicarbonate (KRB) buffer containing 16.7 mM of glucose with somatostatin (2 micrograms/ml) or/and diltiazem HCl (2 x 10(-5) M). Somatostatin inhibited preferentially the early phase of glucose-induced insulin release, whereas diltiazem HCl inhibited the late one. And the concomitant presence of the submaximal concentration of somatostatin (2 micrograms/ml) and diltiazem HCl (2 x 10(-5 M) provided the completely additive inhibition of glucose-induced insulin release. Rat pancreatic islets were incubated with KRB buffer supplemented with 16.7 mM of glucose and 45CaCl2 (10 muCi/ml) for 5--60 min and the biphasic 45Ca uptake by pancreatic islets was obtained. Somatostatin (500 ng/ml-4 micrograms/ml) gave the suppressive effect on the early phase of glucose-induced 45Ca uptake, but the higher concentration (2 micrograms/ml) of somatostatin did not impair the late phase of 45Ca uptake by pancreatic islets. On the other hand, diltiazem HCl did suppress the late phase of glucose-induced 45Ca uptake dose-dependently, but did not suppress the early phase (2 x 10(-5) M). These data indicate that somatostatin suppresses the early phase of glucose-induced Ca2+ uptake preferentially to the late one and has a different action mechanism from Ca antagonist on glucose-induced insulin release.

Animals↗
PubMed1978

Cadmium toxicity and liver mitochondria. I. Different effects of cadmium administered in vivo to adult, young, and ethionine-fed rats.

The changes in liver mitochondrial respiratory activities and cytochrome concentrations were investigated when cadmium chloride was administered orally to adult, young, and ethionine-fed rats. Following a seven-day administration of 30 ppm cadmium in drinking water, adult rats showed no change, while young rats and ethionine-fed rats exhibited a marked increase in mitochondrial respiration with concomitant decrease of respiratory control index and P/O ratio. The concentrations of cytochromes aa3, b, and c + c1 in liver mitochondria were unchanged in adult rats, but increased significantly in ethionine-fed rats. In young rats receiving cadmium the liver mitochondrial protein increased with a slight change in the cytochrome concentration in mitochondria. It was further found that in adult rats a higher concentration (300 ppm) of cadmium in drinking water was toxic to the liver mitochondrial functions. Thus, the effect of oral administration of cadmium on the liver mitochondrial function depends on the condition of the animals.

Aging↗
PubMedDate not supplied

Glomerular clearance and tubular reabsorption of IgG1 and IgG4 in microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM).

The alteration in glomerular clearance (GC) and tubular reabsorption (TR) of IgG subclass (IgG1 and IgG4, same molecular weight, but differing charge) was investigated in 14 microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM) by inhibiting TR of proteins by L-arginine infusion; 16 healthy volunteers served as controls. In healthy volunteers, GC was in the following order: IgG1 > IgG4 > or = albumin. In microalbuminuric patients, as compared with control, GC of albumin was increased significantly; the GC of IgG4 was twice that of control, while GC of IgG1 decreased reciprocally. The TR in controls was in the following order; albumin > IgG1 > IgG4. In microalbuminuric patients, TR of albumin was significantly reduced, TR of IgG1 was moderately reduced and that of IgG4 remained at same level as controls. These observations suggest that the enhancement of GC of albumin in NIDDM was produced by an impaired glomerular anionic charge barrier, while the mechanism for the reduction in TR of albumin was attributable to other undefined mechanisms.

Adult↗
PubMedDate not supplied

The etiology of microalbuminuria in early non-insulin-dependent diabetes mellitus.

Glomerular or tubular contribution for microalbuminuria was estimated by assessing albumin excretion rate (AER) in glomerular urine obtained by L-arginine infusion (AI) and glomerular filtration rate (GFR) in 20 non-insulin-dependent diabetes mellitus (NIDDM) patients before and after glycemic control, and in 19 age-matched controls. Glycemic control normalized AER during AI, while it decreased AER before AI, though it was still above normal. Glycemic control increased tubular reabsorption rate of albumin, but it was still less than normal. Tubular reabsorption rate of albumin declined in close relation with duration of diabetes mellitus, while AER in glomerular urine had no correlation with the duration. GFR had no correlation with AER before or during AI. In conclusion, impaired tubular reabsorption of albumin plays a key role for microalbuminuria in NIDDM.

Adult↗
PubMedDate not supplied

Comparison of renal hemodynamics in early non-insulin-dependent and insulin-dependent diabetes mellitus.

The differences in deranged renal hemodynamics in non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) have never been fully investigated. Whether or not autoregulatory mechanism of renal hemodynamics in NIDDM and IDDM is preserved remains to be clarified. In the present study we directly compared renal hemodynamics and its autoregulatory function in the early stage of NIDDM and IDDM before and after short-term glycemic control. Before glycemic control, mildly exaggerated glomerular filtration rate (GFR), subnormal renal plasma flow (RPF), and elevated filtration fraction (FF) were found in NIDDM as well as in IDDM; but there were no differences in these parameters of renal hemodynamics between the two types of diabetics. Glycemic control decreased GFR, whereas it did not alter RPF, resulting in normalization of FF in NIDDM and in IDDM. Before glycemic control, mean blood pressure was significantly correlated with GFR, but was not correlated after glycemic control in either type of diabetes. In conclusion, hyperglycemia induced glomerular hyperfiltration evenly and disturbed autoregulation of renal hemodynamics in NIDDM and in IDDM.

Adult↗