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Biomedical subjects

F Takao

Publications and source records attributed to F Takao.

16 recordsLinked to original sources
PubMed2002

Mosapride, a 5HT-4 receptor agonist, improves insulin sensitivity and glycaemic control in patients with Type II diabetes mellitus.

AIMS/HYPOTHESIS: We investigated the potential role of mosapride, a 5HT-4 receptor agonist, in glycaemic control in Type II (non-insulin-dependent) diabetic mellitus patients without autonomic neuropathy. METHODS: Thirty-four inpatients with Type II diabetes mellitus were randomly assigned to receive either mosapride (5 mg orally three times a day, n=17) or a placebo ( n=17) for 1 week (first study). Changes in blood glucose and insulin were determined basally as well as after intravenous glucose loading. Insulin sensitivity was evaluated during hyperinsulinaemic-normoglycaemic-clamp studies and by measuring the number of and the autophosphorylation of insulin receptors on the erythrocytes of patients ( n=9). Sixty-nine outpatients with Type II diabetes were similarly treated with mosapride or a placebo for 8 weeks (second study). Finally, tissue- specific expression of 5HT-4 receptors was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Mosapride lowered fasting blood glucose and fructosamine concentrations ( p<0.05) (first study). It significantly increased the number of (Mosapride 3323+/-518 vs 4481+/-786 [ p<0.05], Control 4227+/-761 vs 3275+/-554 per 300 microl erythrocytes) and the tyrosine autophosphorylation (Mosapride 3178+/-444 vs 4043+/-651 [ p<0.05], Control 3721+/-729 vs 3013+/-511 insulin receptor unit) of insulin receptors, as well as glucose utilisation (Mosapride 4.92+/-0.53 vs 5.88+/-0.72 [ p<0.05], Control 4.74+/-0.65 vs 4.70+/-0.31 mg/kg x min). Mosapride treatment for 8 weeks significantly reduced fasting glucose (9.91+/-0.34 vs 8.51+/-0.34 mmol/l, p<0.05), insulin (53.2+/-4.62 vs 40.8+/-5.52 pmol/l, p<0.05) and HbA(1c) (8.61+/-0.20 vs 7.67+/-0.19%, p<0.01) concentrations (second study). The RT-PCR analysis demonstrated specific expression of 5HT-4 receptors in the muscle, but not in the liver or fat tissues. CONCLUSIONS/INTERPRETATION: Mosapride could improve insulin action at muscle and glycaemic control in Type II diabetic patients.

Base Sequence↗
PubMed2000

Erythromycin improves glycaemic control in patients with Type II diabetes mellitus.

AIMS/HYPOTHESIS: Erythromycin mimics the effect of the gastrointestinal hormone motilin by binding to its receptor and acting as a motilin agonist. We recently found that motilin stimulates insulin secretion at lower doses than doses required to stimulate gastric contractile activity. We studied the effects of erythromycin on insulin secretion and glycaemic control in patients with diabetes mellitus. METHODS: Inpatients (n = 34) with Type II (non-insulin-dependent) diabetes mellitus were randomly assigned to receive either erythromycin (400 mg orally three times a day, n = 19) or a placebo (n = 15) for 1 week (first study). Another 34 outpatients with Type II diabetes were also treated with erythromycin (200 mg orally three times a day, n = 17) or a placebo (n = 17) for 4 weeks (second study). Finally, nine inpatients with Type II diabetes and eight normal control subjects received intravenous erythromycin (10 mg x kg(-1) x h(-1)) or saline infusion and insulin secretion was examined (third study). RESULTS: Erythromycin lowered fasting blood glucose and fructosamine concentrations (p < 0.01) and increased basal as well as glucose-stimulated insulin secretion (p <0.05-0.01) (first study). Low doses of erythromycin treatment for 4 weeks also significantly improved glycaemic control in Type II diabetic patients (second study). Erythromycin infusion significantly increased plasma insulin and decreased glucose concentrations in Type II diabetic and control subjects and greatly potentiated glucose-induced insulin secretion in the latter (third study). CONCLUSION/INTERPRETATION: These results indicate that erythromycin given orally has an antidiabetogenic effect and therefore erythromycin derivatives that lack the antibacterial activity could have a therapeutic value in Type II diabetic patients.

Blood Glucose↗
PubMed1996

[Therapeutic trials with topical capsaicin cream and iontophoretically applied lidocaine for diabetic painful truncal neuropathy].

We report a 63-year-old man with a history of diabetes mellitus for 23 years. Painful dysesthesia developed in his toes and trunk with weight loss of 2kg in two months, after the therapy for diabetes mellitus. Truncal painful dysesthesia was symmetrically distributed in the bilateral posterior and anterior T8-11 dermatomes, sparing the bilateral lateral tholacic areas. Electromyography showed denervation potentials in bilateral abdominal rectus muscles at the levels of Th8-10. Histopathological study of the biopsied right sural nerve revealed small fiber neuropathy. We suspected the truncal painful dysesthesia of this patient resulted from diabetic small fiber polyneuropathy, which was resistant to ordinary medical treatments such as non-steroidal anti-inflammatory drugs. Capsaicin cream containing 0.075% capsaicin, and lidocaine delivered by iontophoresis were both effective for his painful dysesthesia.

Capsaicin↗
PubMed1995

Development of insulin-dependent diabetes mellitus in [(NOD + BALB/c) --> NOD] mixed allogeneic bone marrow chimeras.

To examine the possibility that the bone marrow cells of BALB/c genotype interfere with the development of insulitis and diabetes in NOD mice, we transplanted BALB/c bone marrow cells mixed with NOD bone marrow cells into NOD mice. The [(NOD + BALB/c) --> NOD] chimeras developed insulitis and diabetes, indicating that BALB/c bone marrow cells do not interfere with the development of the disease in NOD mice. Surprisingly, these mice have been reconstituted with only NOD hematolymphoid cells. When the pancreatic tissues from newborn NOD and BALB/c mice were grafted into [(NOD + BALB/c) --> NOD] chimeras, the BALB/c pancreatic tissues were rejected, whereas the NOD graft showed insulitis. Furthermore, the spleen cells of the chimeras showed responsiveness to BALB/c spleen cells in mixed lymphocyte reaction and generated cytotoxic T lymphocytes specific for the H-2d and third party targets. These findings indicate that the hematolymphoid cells (including hemopoietic stem cells) of NOD mice are more resilient than those of normal BALB/c mice, and that insulin-dependent diabetes mellitus will recur after bone marrow transplantation unless the hematolymphoid cells of NOD mice are completely destroyed by irradiation.

Animals↗
PubMed1993

New fluorinated dopamine D2 ligands with benzofuran skeleton. The synthesis and in vitro evaluation.

New fluorinated ligands with N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,3-dihydrobenzofuran-7-carboxamide skeleton, which are useful as a prototype to develop 18F labelled in vivo radiotracer for positron emission tomography (PET), were synthesized, and their binding affinities for the dopamine D2 receptors were investigated. Fluorine atom was introduced at C-4 of the pyrrolidine ring (10) or at ethyl substituent at C-5 of the dihydrobenzofuran moiety (20). The in vitro IC50 values of these ligands for the dopamine D2 receptors which were determined by their ability to inhibit the binding of [3H]spiperone binding in rat striatal membrane were 17 and 36 nM, respectively. Thus, the fluorinated compounds 10 and 20 may be possible candidates for further in vivo investigation.

Animals↗
PubMed1991

Differential effects of prolonged hyperglycemia on in vivo and in vitro insulin secretion in rats.

The purpose of this study was to investigate the effects of a 48-h glucose (30% wt/vol) infusion in unrestrained catheterized healthy rats (HG) on subsequent in vivo and in vitro insulin response to glucose. High hyperglycemia (400-450 mg/dl) and resulting hyperinsulinemia (1.2 +/- 0.1 mU/ml vs. 0.15 +/- 0.03 mU/ml in controls) were maintained throughout the infusion period. Glucose-induced insulin secretion was examined in vivo 3 h after the end of infusion by performing either a glucose tolerance test or a hyperglycemic clamp (225 mg/dl for 60 min). In addition, in vivo insulin secretion was studied on day 1, 3, 5, and 7 after the end of glucose infusion by performing glucose tolerance tests. Insulin secretion was also investigated in vitro, using the isolated perfused pancreas technique, 3 h and 1 day post glucose infusion. During glucose tolerance tests and hyperglycemic clamps performed at 3 h, insulin secretion was much greater in HG rats than in controls, and remained increased until day 5. By contrast, when studied in vitro 3 h after the end of the infusion, glucose-induced insulin release from isolated perfused pancreases was impaired in HG rats as compared with controls, and the insulin response to arginine was dramatically increased. However, insulin secretion in vitro returned partially to normal after day 1. These data indicate that prolonged hyperglycemia has quite different effects on the subsequent insulin secretion in vivo or in vitro. It impairs, but reversibly, glucose-induced insulin secretion in vitro, whereas it increases it durably in vivo. This suggests that humoral and/or nervous interferences can counterbalance the possible perturbing effects of prolonged hyperglycemia on the normal B cell responsiveness to glucose.

Animals↗
PubMed1990

Hyperinsulinaemia increases insulin action in vivo in white adipose tissue but not in muscles.

The effect of 4 days of stable hyperglycaemia and resulting hyperinsulinaemia on insulin-induced glucose utilization by individual rat tissues was studied in vivo. The treatment produced a net increase in the glucose utilization index under both basal and insulin-stimulated (euglycaemic/hyperinsulinaemic clamp) conditions in white adipose tissue. On the contrary, glucose utilization was unchanged in aerobic muscles but was decreased in glycolytic skeletal muscles during the clamp.

Adipose Tissue↗
PubMed1990

Organ-specific and systemic autoimmune diseases originate from defects in hematopoietic stem cells.

Transplantation of bone marrow cells from nonobese diabetic (NOD) mice, a model for type 1 diabetes mellitus, to C3H/HeN mice, which express I-E alpha molecules and have aspartic acid at residue 57 of the I-A beta chain, induced insulitis followed by overt diabetes in the recipient C3H/HeN mice more than 40 weeks after bone marrow transplantation. When cyclosporin A, which perturbs T-cell functions, was injected intraperitoneally into [NOD----C3H/HeN] chimeric mice daily for 1 month, the chimeric mice developed insulitis and overt diabetes within 20 weeks following bone marrow transplantation. Transplantation of bone marrow cells from (NZW x BXSB)F1 mice, which develop lupus nephritis, myocardial infarction, and idiopathic thrombocytopenic purpura, into C3H/HeN or C57BL/6J mice induced in the recipient strains both lupus nephritis and idiopathic thrombocytopenic purpura more than 3 months after transplantation. Transplantation of a stem-cell-enriched population from (NZW x BXSB)F1 mice into normal mice also induced autoimmune disease in the recipients. These results indicate that both systemic autoimmune disease and organ-specific autoimmune disease originate from defects that reside within the stem cells; the thymus and environmental factors such as sex hormones appear to act only as accelerating factors.

Animals↗
PubMed1990

Maintenance of pancreatic endocrine B cells of neonatal rat: Part-XIV--Effect of maternal hyperglycemia on the secretion of insulin and glucagon.

Effects of gestational hyperglycemia on A and B cells were examined in pancreatic monolayer islet cell cultures of neonatal rats from mothers of normoglycemia (C) and made slightly (SH), moderately (MH) and highly hyperglycemic (HH) by streptozotocin injection. Monolayer cultures were maintained for 7 days in the medium with 5.5 mM glucose plus 1 mM 2-deoxyglucose. On day 0, B cells of the SH group were more responsive to glucose and 2-ketoisocaproate than those of other groups. On day 7, the response of B cells in the C and SH groups was remarkably enhanced, thus displaying a dose-dependent increasing pattern of insulin secretion in response to glucose, 2-ketoisocaproate and arginine, and a convex-type secretion to leucine. However, there was no response by B cells in the MH and HH groups. Further, a dose-dependent inhibition of glucagon secretion due to glucose was seen in A cells of the C and SH groups on day 0 and day 7. The responses of these A cells to other nutrients were slightly decreased or were of a low convex-type. In the MH group, however, the glucagon secretion was remarkably enhanced due to leucine and 2-ketoisocaproate on day 0 and day 7, and due to arginine on day 7, although it remained suppressed by glucose. A cells of the HH group were unresponsive through the whole culture period. These results suggest that the development of A- and B-cell responses in vitro of neonates was differently affected by the degree of maternal hyperglycemia.

Animals↗
PubMed1990

Histogenesis of hemopoietic bone marrow in adult mice.

Based on the concept that the hierarchy of regulatory genes may specify mammalian development, we attempted to evaluate how morphological and functional phenotypes of hemopoietic bone marrow develop in murine models. From studies of local irradiation, s.c. implantation of bone with or without marrow, and renal subcapsular implantation of marrow plugs or bone without marrow, we identified four sequential (necrotic, clearing, stromal proliferating, and hemopoiesis-recovering) responses in the early phase of the reconstruction of hemopoietic marrow that spatially and temporally proceeded in this restricted order. In addition, characteristic hexagonal sinuses were found to participate in the development of hemopoietic marrow in the early phase. The development of hexagonally arranged sinuses seems to coincide with the formation of abundant osseous trabeculae and to precede the appearance of colony-forming units in culture (CFU-C) and spleen colony-forming units (CFU-S). These findings are discussed from the point of the hierarchy of regulation.

Animals↗
PubMed1989

[The effect of maternal hyperglycemia on insulin secretion by monolayer-cultured B cells of neonatal rats--a perifusion study].

To evaluate the effect of maternal hyperglycemia on insulin secretion by neonatal rat B cells, perifusion was conducted on monolayer cultures of rat neonates from normoglycemic (C) mothers or those made slightly (SH) and highly (HH) hyperglycemic by the injection of streptozotocin. In the C, SH and HH groups, B cells responded to 16.7 mM glucose, 10 mM leucine, 10 mM 2-ketoisocaproate and 10 mM arginine in a biphasic manner, although these nutrients provided stimuli so feeble that insulin secretion in the second phase was slightly raised above basal levels. However, quantitative relationships differed. Compared with the C group, B cells in the SH group showed a significant increase in the secretion of the second phase in response to glucose, 2-ketoisocaproate and arginine but not to leucine, whereas there was no difference in the secretion of the first phase between these two groups. In the HH group, a lower insulin secretion of the first and second phase was observed. These results are compatible with hyperglycemia-hyperinsulinaemia theory concerning the function of B cells in neonates born to slightly hyperglycemic mothers and with a defect in insulin secretion by neonates from highly hyperglycemic females.

Animals↗
PubMed1988

Effect of maternal hyperglycaemia on insulin secretion by monolayer cultures of pancreatic cells from neonatal rats: a perifusion study.

The effect of maternal hyperglycaemia on the function of neonatal B cells was examined using a perifusion technique in pancreatic monolayer cultures of neonatal rats from normoglycaemic mothers (C), and those made slightly hyperglycaemic (SH) and highly hyperglycaemic (HH) by injection of streptozotocin. Monolayer cultures were kept for 7 days in medium containing 5.5 mmol glucose/1 plus 1 mmol 2-deoxy-glucose/1. On day 0, B cells in the C group responded to 16.7 mmol glucose/1, 10 mmol leucine/1 and 10 mmol 2-ketoisocaproate/1 in a monophasic fashion with no significant rise in the second phase. However, compared with the C group, a significant increase in the second-phase secretion in response to glucose and 2-ketoisocaproate was observed in the SH group, although there was no difference in the first-phase secretion. In the HH group the insulin secretion was lower in the first phase but not in the second phase. After culture for 7 days, B cells in the C group showed a biphasic response to the secretagogues, with a great increase in the second-phase secretion. In the SH group, the second phase of insulin secretion was increased but the increment was far less than that in the C group. The secretory response was remarkably low in the HH group compared with other groups. From these results, we conclude that at an early stage of culture slight maternal hyperglycaemia causes a hypersensitivity of neonatal B cells but impairs the normal development of the function of B cells during culture, and that high hyperglycaemia results in impaired insulin secretion throughout the whole period of culture studied.

Animals↗
PubMedDate not supplied

An epidemiologic study on the correlation between salt threshold, academic test marks, biochemical data, number of complaints, and personality in women college students.

One hundred nine 19-year-old female students were surveyed as to academic test marks; salt detection and recognition thresholds; serum cholesterol, serum uric acid, serum cortisol, and other biochemical indices in serum; urinary sodium/creatinine and potassium/creatinine, as well as number of complaints based on the Cornell Medical Index (CMI) and personality based on the Yatabe-Guilford (Y-G) test. The salt recognition threshold showed a high negative correlation with serum uric acid concentration and a slight correlation with CMI complaint number, academic test marks, blood pressure, obesity, and serum cholesterol. The subjects with high salt thresholds had relatively passive personalities. Cholesterol, uric acid, hemoglobin, ferritin, and glucose levels in the serum were higher in the group with higher academic marks. These students also had fewer complaints and more of them were type B individuals based on the Y-G test. They also seemed to be under greater stress. In regression analysis, the partial regression coefficient between academic test marks and serum cholesterol was 60 percent higher than that between academic test marks and serum uric acid. Students who lived on campus had 24.8 milligrams per deciliter (15.7 percent) more serum cholesterol and 3.8 micrograms per deciliter (37.7 percent) more serum cortisol than those who commuted from home.

Achievement↗