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Biomedical subjects

A Iguchi

Publications and source records attributed to A Iguchi.

269 records · Page 15Linked to original sources
PubMed1984

Differential plasma glucose response to varying glucose loads in non-insulin dependent (type 2) diabetics with retinopathy.

In order to examine a possible diabetic disturbance in the buffer mechanism in the liver for the caloric supply, different amounts of glucose (30 and 100 g) were given orally and the plasma glucose and IRI were compared between type 2 diabetics without retinopathy and those with retinopathy. In the diabetics without retinopathy, the time course change in the plasma glucose levels were not significantly different between the 100 g and 30 g OGTT, while in those with retinopathy the increments of plasma glucose levels were influenced by the variation of glucose load. The additional insulin secretions were similar after 30 g and 100 g OGTT in the diabetics with retinopathy, while in those without retinopathy the amounts of insulin secretions on the 100 g OGTT were larger than those observed after 30 g OGTT. These facts suggest that the liver of diabetics with retinopathy, in contrast to that in diabetics without retinopathy, cannot buffer the fuel supply against varying amounts ingested.

Blood Glucose↗
PubMed1984

Glucoregulatory effects of intrahypothalamic injections of bombesin and other peptides.

The influence of neuropeptides on hypothalamic regulation of plasma glucose and pancreatic hormone secretion was studied in anesthetized rats. Neuropeptides were injected directly into the ventromedial hypothalamus (VMH) and the lateral hypothalamic area (LHA) and changes in hepatic venous plasma glucose, insulin, and glucagon concentrations were studied. Injection of bombesin into the VMH resulted in a marked and sustained hyperglycemia in the hepatic venous plasma, which was also observed after injection into the LHA. Microinjection of SRIF into the VMH or LHA caused a decrease in hepatic venous plasma glucose concentration. Injection of neurotensin into the VMH or LHA resulted in a transient release of insulin in the 10-min postinjection samples. In 30- and 60-min postinjection samples, significant increases in glucagon concentrations were observed after substance P injection into the VMH or LHA. No major difference in the plasma glucose, insulin, or glucagon concentrations was observed when VMH and LHA stimulation was compared. These data suggest that glucoregulatory neuropeptides may act on the VMH and LHA, which do not necessarily follow the currently recognized anatomical boundaries.

Animals↗
PubMed1983

Effects of octanoate and acetate upon hepatic glycolysis and lipogenesis.

Octanoate and N6,O2'-dibutyryl adenosine 3',5'-monophosphate (dibutyryl cyclic AMP) cause a marked inhibition of net glucose utilization and lactate and pyruvate accumulation by hepatocytes isolated from meal-fed rats. Acetate is much less effective as an inhibitor of glycolysis. Fatty acid synthesis, as measured by tritiated water incorporation, is inhibited by dibutyryl cyclic AMP, whereas it is stimulated by 10 mM acetate and 1 mM octanoate. Stimulation of fatty acid synthesis by 1 mM octanoate, however, is lost paradoxically at higher concentrations of octanoate. Rates of fatty acid synthesis estimated by [1-14C]octanoate incorporation were consistently higher than rates calculated on the basis of tritiated water incorporation, raising the question as to which is the better index of the rate of de novo fatty acid synthesis. The effects of octanoate were studied because it was reasoned that this fatty acid should not inhibit acetyl-CoA carboxylase but should inhibit glycolysis and supply acetyl-CoA for lipogenesis. This was found to be the case, proving that glycolytic activity is not necessary for rapid rates of de novo fatty acid synthesis by liver.

Acetates↗
PubMed1983

Vagotomy or atropine blocks hypoglycemic effect of insulin injected into ventromedial hypothalamic nucleus.

Stereotaxic microinjections of insulin (100 microU) into the ventromedial hypothalamic nucleus (VMN) resulted in rapid decrease, whereas injection of control saline into the same region caused a slight increase of hepatic venous plasma glucose concentration in rats. The hypoglycemic effect of insulin injected into the VMN was eliminated by pretreatment of the animals with atropine but not with propranolol or with phentolamine. Subdiaphragmatic vagotomy also prevented the decrease of hepatic venous plasma glucose concentration seen after microinjection of insulin into the VMN. These results support the hypothesis that the VMN is an insulin-sensitive glucoregulator center or that it is part of one and that the glucoregulatory impulse that originates in the VMN reaches the effector organ, the liver, through the cholinergic fibers of the vagus nerves.

Animals↗
PubMed1981

Decrease in plasma glucose concentration after microinjection of insulin into VMN.

The influence of insulin on hypothalamic regulation of blood sugar homeostatis was studied in anesthetized rats. Insulin was injected directly into the ventromedial hypothalamic nucleus (VMN), the lateral hypothalamic area (LHA), the parietal cortex, or the third cerebral ventricle, and changes in hepatic venous plasma glucose concentrations were studied. After injection of 100 microU insulin into the parietal cortex or the third ventricle, hepatic venous plasma glucose concentration did not differ from that of the control rats, which received saline injection into the same CNS regions. Saline injection into the LHA raised the hepatic venous plasma glucose concentration in control rats, where injection of 100 microU insulin into the LHA resulted in a modest but significant decrease of glycemia in the 2-, 5-, and 10-min postinjection samples. As little as 10 microU insulin injected into the VMN eliminated the hyperglycemic response seen in control rats after saline injection into this site. The divergence between insulin-treated rats and their saline-treated controls was further amplified, and an actual fall of plasma glucose was observed in rats given injections of 50 or 100 microU insulin into the VMN. Increasing quantities of insulin (from 10 to 100 microU) injected into the VMN resulted in graded decreases of hepatic venous plasma glucose concentrations, suggestive of a dose-response curve. These observations support the hypothesis that the VMN and the LHA are parts of an insulin-sensitive CNS glucoregulator system that exerts influences on the systemic blood glucose levels by causing rapid alterations in hepatic glucose metabolism.

Animals↗
PubMed1979

Transjugular hepatic vein cannulation in rats with nonisotopic in vivo verification.

A simple, rapid and relatively atraumatic method for transjugular cannulation of the hepatic vein and for repeated sampling of hepatic venous blood in the rat is described. Preliminary in vivo verification of the cannula's position is proposed, either by using the glucose differential between consecutive samples of the hepatic venous blood and inferior vena cava blood, or more practically, by using the glucose differential between the hepatic venous blood and tail blood obtained simultaneously. The latter procedure is favored because of its technical simplicity.

Animals↗
PubMedDate not supplied

Effects of enalapril and L-158809 on myocardial beta-adrenergic receptor density in transplanted rat hearts.

BACKGROUND: We compare the effects of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II type 1 (AT(1)) receptor blocker on density of myocardial beta-adrenergic receptors (beta-ARs) in a heterotopic heart transplantation model. METHODS: Hearts of F344 rats were heterotopically transplanted into Lewis rat recipients immunosuppressed with cyclosporine (10 mg/kg/day). Recipients were treated orally with the AT(1) receptor blocker L-158809 (3 mg/kg/day, n = 6), enalapril (3 mg/kg/day, n = 6), or vehicle only (n = 6) for 90 days. Density of myocordial beta-ARs was determined with an autoradiographic technique using [(3)H]CGP-12177. RESULTS: Graft status, the sum of the functional score and the score for color, was preserved better in the L-158809-treated group (5.8 +/- 0.9) and in the enalapril-treated group (5.6 +/- 0.8) than in the vehicle-treated group (3.8 +/- 0.9, p < 0.05). The grades of graft coronary artery disease in the L-158809-treated group and in the enalapril-treated group were significantly less than that seen in the vehicle-treated group. The density of myocardial beta-AR (fmol/mg of protein) was 3.5 +/- 0.5 in the L-158809-treated group (p < 0.05 vs. vehicle-treated group) and 3.2 +/- 0.5 (p < 0.05) in the enalapril-treated group but was 2.2 +/- 0.4 in the vehicle-treated group. CONCLUSION: L-158809 is as effective as enalapril in restoring myocardial beta-AR density in immunosuppressed rat transplant model, and this efficacy, as well as the prevention of graft coronary arteriosclerosis, is probably associated with the preservation of graft status.

Angiotensin Receptor Antagonists↗
PubMedDate not supplied

Pharmacological studies on the hypoglycemic effect of 7,8-dihydro-2-(4-methylpiperazinyl)-4-(1-pyrrolidinyl)-6H-thi opyrano [3,2-d] pyrimidine dimaleate (MTP-1307), a novel hypoglycemic agent.

MTP-1307, 7,8-dihydro-2-(4-methylpiperazinyl)-4-(1-pyrrolidinyl)-6H- thiopyrano[3,2-d]pyrimidine dimaleate, is a novel oral hypoglycemic agent, structurally different from any existing hypoglycemic drugs. In fasted rats, the hypoglycemic effect of MTP-1307 was accompanied by elevation of the plasma insulin. In glucose tolerance tests, MTP-1307 suppressed the hyperglycemia after glucose loading and significantly enhanced the glucose-induced insulin secretion. In isolated hepatocytes from fasted rats, MTP-1307 inhibited gluconeogenesis from lactate and alanine. Furthermore, MTP-1307 increased the lactate/pyruvate ratio but did not increase the lactate level. MTP-1307 did not influence glycogenolysis in isolated hepatocytes from fed rats. In genetically diabetic ob/ob mice, MTP-1307 decreased the blood glucose level and improved glucose tolerance, but did not affect the level of plasma insulin. MTP-1307 increased 14CO2 production from glucose in isolated epididymal fat pads of ob/ob mice. Thus, these findings suggest that MTP-1307 produces hypoglycemic activities not only in normal animals but also in genetically diabetic animals, and that the hypoglycemic mechanism of MTP-1307 involves the promotion of glucose utilization in adipose tissue and, partially, the inhibition of gluconeogenesis in the liver and the stimulation of insulin release from the pancreas.

Adipose Tissue↗
PubMedDate not supplied

Effects of cyclosporine and 15-deoxyspergualin on coronary arteriosclerosis after heart transplantation in the rat.

The development of graft coronary arteriosclerosis remains a serious consequence after heart transplantation and may limit long-term survival. The purpose of this study was to evaluate the effects of 15-Deoxyspergualin on graft coronary arteriosclerosis after heterotopic heart transplantation in a rat model and compare the effects to those of cyclosporine treatment. Two groups of Lewis rats (n = 7 each group) underwent heterotopic heart transplantation from Fischer 344 donors and were treated with either cyclosporine (10 mg/kg/day) or 15-Deoxyspergualin (3 mg/kg/day). Histologic evaluations of rejection (scale: 0 = none, 3 = severe) and graft coronary arteriosclerosis (scale: 0 = normal, 4 = occluded) were made 60 days after transplantation. No significant difference was found between the two groups with respect to the degree of rejection (2.0 +/- 0.7 in the cyclosporine-treated group versus 2.0 +/- 0.5 in the 15-Deoxyspergualin-treated group). However, the extent of graft coronary arteriosclerosis in the 15-Deoxyspergualin-treated group was significantly less than that seen in the cyclosporine-treated group (1.11 +/- 0.34 versus 1.71 +/- 0.24, p < 0.01). Furthermore, the incidence of diseased vessels among all observed vessels was significantly lower in the 15-Deoxyspergualin-treated group compared with the cyclosporine-treated group (63% +/- 12% versus 76% +/- 7%, p < 0.05). Although the protective mechanism of 15-Deoxyspergualin is unknown, it most likely possesses a different immunosuppressive mechanism of action from cyclosporine. We concluded that 15-Deoxyspergualin is superior to cyclosporine in preventing graft coronary arteriosclerosis after heart transplantation.

Abdomen↗
PubMedDate not supplied

Lung reperfusion injury is reduced by inhibiting a CD18-dependent mechanism.

CD18 designates a component of a leukocyte surface glycoprotein complex that mediates endothelial adherence. To determine whether interference with CD18-dependent leukocyte adhesion modifies reperfusion injury, we transplanted 16 canine left lungs after 4-hour preservation with modified Euro-Collins solution. Anti-canine CD18 monoclonal antibody (R15.7, 1 mg/kg, intravenously) was administered to eight lung recipients 5 minutes before reperfusion; eight control recipients were not treated. Ventilation was identical in donor-recipient pairs (tidal volume, 600 ml; fraction of inspired oxygen, 0.53; positive end-expiratory pressure, 5 cm H2O). Respiratory and inert gas exchange and hemodynamics were assessed in left lung donors one-half hour after right lung exclusion and in allograft recipients at 0.5, 1.5, 2.5, 3.5, and 6.0 hours after transplantation and right lung exclusion. Reperfusion injury was evident in both recipient groups at 6 hours after transplantation, but inert gas shunt was lower in monoclonal antibody-treated dogs (13% +/- 6%) than in controls (30% +/- 17%, p < 0.05); comparisons of arterial blood gases in monoclonal antibody recipients (PaO2, 209 +/- 83 mm Hg; PaCO2, 45 +/- 7 mm Hg) and controls (PaO2, 108 +/- 54, p < 0.05; PaCO2, 64 +/- 25, p < 0.05) at 6 hours indicated that monoclonal antibody administration distinctly improved respiratory gas transfer. Gravimetric lung water was less in monoclonal antibody recipients (5.78 +/- 1.01 ml/kg) than in controls (8.02 +/- 1.90 ml/kg, p < 0.05), but lung compliance at 6 hours was equally reduced in monoclonal antibody recipients (40 +/- 9 ml/cm H2O) and in controls (39 +/- 7 ml/cm H2O, p = not significant). Pulmonary vascular resistance doubled immediately after transplantation but was identical in monoclonal antibody-treated dogs (890 +/- 168 dynes.sec.cm-5) and in controls (874 +/- 162 dynes.sec.cm-5, p = not significant) at 6 hours. We conclude that inhibition of CD18-dependent leukocyte function attenuates the development of both shunt and abnormal respiratory gas exchange in lung reperfusion injury. Significant physiologic abnormalities occurred despite R15.7 treatment and may represent inadequate preservation or the effect of CD18-independent adhesion mechanisms.

Animals↗