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Y Shiba

Publications and source records attributed to Y Shiba.

At least 37 records · Page 2Linked to original sources
PubMed1999

Modulation of carbachol-induced Cl(-) currents and fluid secretion by isoproterenol in rat submandibular acinar cells.

The effects of muscarinic and beta-adrenergic agonists on Cl(-) currents in acinar cells were investigated to clarify their role in the regulation of fluid secretion in rat perfused submandibular glands. Additions of isoproterenol (IPR) at 10(-8) to 10(-6) M and 8-(4-chlorophenylthio)-cyclic AMP (CPT-cAMP) at 10(-3) M to the perfusate suppressed carbachol (CCh; 10(-6) M)-induced fluid secretion. IPR and CPT-cAMP also diminished CCh-induced oscillatory Cl(-) current and increased CCh-stimulated non-oscillatory Cl(-) current. Propranolol blocked the effect of IPR on fluid secretion. IPR did not modulate the CCh-induced increase in intracellular concentration of calcium ions and intracellular pH in isolated cells. Propranolol blocked IPR-induced changes in Cl(- )currents, while propranolol itself increased CCh-induced K(+) current and reduced CCh-induced oscillatory Cl(-) current. Increasing external osmolarity with 50 mM sucrose abolished IPR-enhanced non-oscillatory Cl(-) current. Neither CCh-induced oscillatory Cl(-) current nor IPR-induced suppression of the oscillatory Cl(-) current was influenced by the hypertonicity. Perfusion of the gland with the hypertonic solution did not affect the IPR-induced suppression of fluid secretion. These results suggest that IPR induces the suppression of CCh-induced oscillatory Cl(-) current and potentiation of the non-oscillatory Cl(-) current via an increase in cyclic AMP level, and that suppression of the oscillatory Cl(-) current by IPR may contribute to the inhibition of fluid secretion from submandibular glands.

Adrenergic beta-Agonists↗
PubMed1999

[Primary ciliary dyskinesia treated with living-donor lobar lung transplantation].

We report a case of primary ciliary dyskinesia in which a living-donor lobar lung transplant was performed. A 24-year-old woman with a diagnosis of primary ciliary dyskinesia and bronchiectasis was admitted to Shinshu University Hospital because of persistent dyspnea and pyrexia over a period of 4 months. Although she was given various antibiotics, neutrophilia, elevated plasma C-reactive protein (CRP) levels, and respiratory failure persisted. Chest roentgenograms and computed tomography disclosed severe bronchiectasis and diffuse infiltrative shadows in both lung fields. Pseudomonas aeruginosa was detected in a sputum culture. Although a variety of conventional therapies were administered, the patient's oxygenation progressively deteriorated. She was intubated and assisted by mechanical ventilation. The patient and her family proposed lung transplantation, and we concluded that a living-donor lobar lung transplant would be a suitable treatment for her disease. We transported the patient to Okayama University Hospital by helicopter 10 days after intubation. A living-donor lobar lung transplant was successfully performed with lung tissues donated by the patient's mother and sister for each transplant site.

Adult↗
PubMed1998

Potentiation by isoproterenol on carbachol-induced K+ and Cl- currents and fluid secretion in rat parotid.

Isoproterenol (IPR) and 8-(4-chlorophenylthio)-cyclic AMP (cpt-cAMP) enhanced carbachol (CCh)-induced fluid secretion from rat parotid glands, but had no effect by themselves. The enhancement by IPR was blocked by propranolol. In dispersed parotid acinar cells, IPR and cpt-cAMP potentiated CCh-induced K+ and Cl- currents (IK and ICl). IPR at the concentration of 0.1 microM significantly potentiated the CCh-induced increase in intracellular Ca2+ concentration ([Ca2+]i), but 1 mm cpt-cAMP did not. The incidence of the potentiation by IPR in CCh-induced Mn2+ entry was 31% and that by cpt-cAMP was 21%. The potentiation by IPR in the ionic currents and the [Ca2+]i was suppressed by propranolol. These results suggest that the CCh-induced fluid secretion from rat parotid glands is enhanced by IPR through the potentiation of IK and ICl mainly by the increased cyclic AMP level and partially by the potentiated Ca2+ influx and [Ca2+]i increase, and that IPR is more effective than cpt-cAMP in the enhancement of the CCh-induced [Ca2+]i increase.

Animals↗
PubMed1998

Growth and morphology of anchorage-dependent animal cells in a liquid/liquid interface system.

In general, anchorage-dependent animal cells cultivated on a solid culture substrate, such as polystyrene, are collected by trypsin treatment. This treatment may have detrimental effects such as the proteolysis of the cell membrane proteins. To avoid these effects, cell cultivation using a liquid/liquid interface system has been investigated. In this cultivation method, the cells grow at the interface between a culture medium and a hydrophobic liquid. In this study, various fluorocarbons (FC-40, FC-70, KPF-91, KPF-102, and KPF-142) were used as substrates for the interface, and the cultivation of fibroblast cells (L-929; the mouse-derived cell line) at the interfaces was investigated. Early in the cultivation period, the growth of L-929 cells depended on the substrate type. Although cell cultivation at the interfaces was possible, it was slower than that at the polystyrene surface. Cell spreading at the interfaces was relatively small, which indicates that cell adhesion at the interfaces may be weak. In particular, the cells at the MEM/FC-70 interface anchored with one another and formed multicellular hemispherical aggregations shaped like spheroids. The difference in the adhesions to the interfaces appears to be dependent on the contaminants contained in the fluorocarbons because the physical properties of the fluorocarbon did not affect the cell growth and adhesion. Moreover, subcultivation from the interfaces to the same interface was possible without trypsin treatment. In this case, the delay of the growth at the interfaces did not occur because the cells were not affected by trypsin treatment.

Animals↗
PubMed1998

Process development for high-level secretory production of carboxypeptidase Y by Saccharomyces cerevisiae.

In order to develop a production process for carboxypeptidase Y (CPY, yeast vacuolar protease) secreted by Saccharomyces cerevisiae KS58-2D, medium composition, culture conditions, and expression systems were investigated. We found that the addition of histidine to thiamine-free medium, in which CPY production was almost negligible, raised the intracellular thiamine level, resulting in the increase of CPY production. On the basis of the choice of an expression system that uses an inducible GAL10 promoter, reassessment of histidine concentration in the medium, and optimization of the pH level during cultivation (pH 6.5), active CPY was secreted in a quantity of over 400 mg/l, which was more than tenfold that higher than that previously reported. The process developed could be easily scaled-up to industrial-scale fermentation.

Biomass↗
PubMed1998

Increased hepatic glucose production and decreased hepatic glucose uptake at the prediabetic phase in the Otsuka Long-Evans Tokushima fatty rat model.

To investigate the time course of the hepatic glucose metabolism in non-insulin-dependent diabetes (NIDDM), we measured hepatic glucose production (HGP) and first-pass uptake of portal glucose infusion by the liver (HGU) using dual-tracer methods in a NIDDM model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, and in normal controls, Long-Evans Tokushima Otsuka (LETO) rats, at 8, 14, and 28 weeks of age (n = 5, respectively). The fasting plasma glucose level in OLETF rats was significantly higher than in LETO rats at 28 weeks of age (8.9 +/- 1.7 v 6.3 +/- 0.4 mmol/L, P < .01), while there was no significant difference at 8 and 14 weeks. Hyperinsulinemia in OLETF rats appeared at > or = 8 weeks of age. Basal HGP was significantly higher in OLETF than in LETO rats at 8 and 28 weeks (8 weeks, 12.7 +/- 1.7 v 9.4 +/- 1.8 mg x kg(-1) x min(-1), P < .05; 28 weeks, 10.9 +/- 1.6 v 7.1 +/- 1.3 mg x kg(-1) x min(-1), P < .01). At 14 weeks, basal HGP was not significantly different between OLETF and LETO rats. However, at all study points, HGU during a portal glucose infusion was significantly lower in OLETF than in LETO rats (8 weeks, 0.9 +/- 0.2 v 2.3 +/- 0.5, P < .01; 14 weeks, 0.8 +/- 0.3 v 1.4 +/- 0.3, P < .05; 28 weeks, 0.7 +/- 0.2 v 1.4 +/- 0.3 mg x kg(-1) x min(-1), P < .01). Fasting plasma free fatty acid (FFA) levels were not significantly different between OLETF and LETO, except at 8 weeks. Suppression of plasma FFA levels by endogenous insulin during a portal glucose infusion was impaired in OLETF rats compared with LETO rats. In summary, this study demonstrates that derangement of hepatic glucose handling, such as increased basal HGP and decreased HGU, is observed in obese NIDDM model OLETF rats at the prediabetic phase when hyperglycemia is still not apparent. Furthermore, these derangements may be accompanied by impaired lipid metabolism.

Animals↗
PubMed1998

Effect of TKS159, a novel 5-hydroxytryptamine4 agonist, on gastric contractile activity in conscious dogs.

A novel 5-hydroxytryptamine (5-HT)4 receptor agonist, TKS159, ¿4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2- hydroxymethyl-4-pyrrolidinyl] benzamide), has recently been developed as a gastroprokinetic drug. Cisapride is already used clinically to increase gastric contractions. The stimulatory effects of TKS159 and cisapride on gastric contractions were examined using force transducers chronically implanted on the vagally denervated pouch (Heidenhain pouch) and the vagally innervated main stomach in conscious dogs. Contractile activity was analysed by computer and expressed as a motor index. Intravenous administration of TKS159 or cisapride significantly increased the motor index in both the main stomach and the Heidenhain pouch during the fed and fasted states. Pharmacological characterization in the fasted state revealed that the contraction-stimulating activity of TKS159 and cisapride on the stomach was significantly inhibited by atropine, hexamethonium and a 5-HT4 receptor antagonist, SDZ 205-557. Granisetron (a 5-HT3 receptor antagonist) significantly inhibited cisapride-induced, but not TKS159-induced gastric contractions. The plasma motilin concentration was significantly increased after cisapride, but not after TKS159 injection. In conclusion, TKS159 has a contractile-stimulating effect on both the innervated and the denervated stomach. It is likely that a cholinergic pathway and 5-HT4 receptors are involved in producing the contractions, although other mechanisms cannot be excluded. Cisapride has almost the same characteristics, but the present findings suggest the involvement of motilin and 5-HT3 receptors in the effects of cisapride.

Animals↗
PubMed1998

High plasma free fatty acids decrease splanchnic glucose uptake in patients with non-insulin-dependent diabetes mellitus.

It has been proposed that high plasma free fatty acid (FFA) levels observed in patients with non-insulin dependent diabetes mellitus (NIDDM) contribute to the development of their insulin resistance. We examined patients with NIDDM to find whether maintaining plasma FFA levels in the fasting range with a euglycemic hyperinsulinemic clamp combined with an oral glucose load (clamp OGL) would affect insulin-mediated peripheral glucose uptake (PGU) and splanchnic glucose uptake (SGU). Nine NIDDM subjects (age, 55 +/- 3 years; duration of diabetes, 11 +/- 2 years; body mass index, 21.0 +/- 0.4 kg/m2; hemoglobin A1c, 9.0 +/- 0.3%; fasting plasma glucose, 9.4 +/- 3.0 mmol/l, means +/- SEM) were hospitalized and treated with diet, oral hypoglycemic agents or insulin for at least 2 weeks to maintain fasting plasma glucose < 8 mmol/l. All the patients were subjected to two different protocols in a random order. On one protocol, under the hyperinsulinemic condition, FFAs were maintained at the their fasting levels (1.19 +/- 0.08) by triglyceride emulsion infusion (Lipid infusion study, L), and on the other protocol, FFAs were made to fall (0.26 +/- 0.06 mmol/l) with saline instead of triglyceride emulsion infusion (Saline infusion study, S). During euglycemic (L, 5.4 +/- 0.2; S, 5.1 +/- 0.2 mmol/l) hyperinsulinemic (L, 1377 +/- 108; S, 1328 +/- 67 pmol/l) clamp, high FFA levels significantly reduced PGU (L, 26.7 +/- 3.6; S, 32.1 +/- 3.4 mumol.kg-1.min-1, P < 0.05) and SGU (L, 12.1 +/- 4.2; S, 27.5 +/- 5.6%, P < 0.05). In conclusion, high FFA levels in patients with NIDDM impaired insulin-mediated glucose uptake in the splanchnic as well as peripheral tissues.

3-Hydroxybutyric Acid↗
PubMed1997

Sensitive, selective gas chromatographic-mass spectrometric analysis with trifluoroacetyl derivatives and a stable isotope for studying tissue sorbitol-producing activity.

One of the major mechanisms involved in diabetic microangiopathy is considered to be an altered polyol pathway. However, clarifying the pathophysiology is difficult due to the lack of a sensitive method for measuring the reduction of glucose to sorbitol in tissue. Here we report a sensitive and selective method for polyol measurement using trifluoroacetyl (TFA) derivatives of polyols and stable isotope-labeled D-sorbitol (U-[13C]sorbitol, 13C6H14O6, 98.7%) as an internal standard. Gas chromatography-mass spectrometry (GC-MS) using an SE-30 capillary column gave elution of TFA derivatives of sugars, polyols and U-[13C]sorbitol within 8 min, with clear separation of sorbitol. In the calibration study, the coefficients of correlation between the amount of sorbitol added and that determined in standard solutions containing 0.1-8.0 nmol sorbitol, erythrocyte mixture and liver cytosol mixture were r = 0.999, r = 0.997 and r = 0.997, respectively. The precision of the GC-MS measurement of standard solution was C.V. = 4.3%. Because glucose is used as a substrate, the method can clarify the polyol pathway under physiological conditions. With this method, Km and Vmax values of the reductase in erythrocytes were 115 +/- 19 mmol/l and 4.42 +/- nmol/min/g of hemoglobin. In human liver, on the other hand, they were 755 +/- 132 mmol/l and 0.773 +/- 0.090 nmol/min/mg of protein, respectively. This difference of Km values suggested that aldehyde reductase rather than aldose reductase is mainly responsible for reducing glucose to sorbitol in the liver. In conclusion, this newly developed method offers a highly sensitive and selective procedure for measuring low concentrations of sorbitol in various tissues and cells and should enable clarification of the kinetics of glucose reduction to sorbitol, which in turn can be used to evaluate the role of an altered polyol pathway in the pathophysiology of diabetic microangiopathy.

Adolescent↗
PubMed1997

Effect of 5-hydroxytryptamine on gastrointestinal motility in conscious guinea-pigs.

Many studies have suggested that 5-hydroxytryptamine (5HT, serotonin) plays an important role in the control of gastrointestinal motility. However, most of these studies have been carried out on guinea-pig ileum in vitro. Therefore, we investigated the mechanisms of action of 5HT on gastrointestinal motility in conscious guinea-pigs. In order to investigate the effects of 5HT on gastrointestinal motility, extraluminal force transducers were sutured onto the serosal surfaces of the gastric antrum, duodenum and ileum and 5HT was infused intravenously. One of three types of 5HT antagonist or atropine was given before a 5HT infusion of 3.0 micrograms kg-1 min-1 was started. Regular cyclic patterns were observed from the gastric antrum to the ileum in both the fasted and fed states. 5HT increased the contraction amplitudes at all sites. 5HT-induced contractions in the gastric antrum and duodenum were significantly inhibited by methysergide, ondansetron and atropine, but not by ketanserin. In the ileum, only atropine inhibited 5HT-induced contractions. These results suggest that 5HT increases the gastrointestinal contraction amplitude mainly via a cholinergic pathway. 5HT3 receptors and 5HT1-like and/or 5HT2C receptors appear to be responsible for 5HT-induced gastric antral and duodenal contractions, but 5HT receptors other than 5HT1-like, 5HT2A, 5HT2C and 5HT3 receptors induce ileal contractions.

Animals↗
PubMed1997

Thiamine increases expression of yeast gene.

We found that CPY production in Saccharomyces cerevisiae KS58-2D/pCY303 was increased by the addition of thiamine into the medium, while the addition of thiamine had no effect on cell growth. It became clear that the positive effect of thiamine was due to transcriptional increase, because the levels of CPYmRNA were increased according to the amount of thiamine added. Furthermore, it was suggested that thiamine generally increases the expression of yeast genes, since the expression of the luciferase gene that was artificially constructed was also increased to some extent by thiamine in S. cerevisiae.

Actins↗
PubMed1997

Augmentation of hepatic glucose uptake by a positive glucose gradient between hepatoportal and central nervous systems.

To determine the role of the glucose gradient between the hepatoportal system (HPS) and the central nervous system (CNS) in regulating hepatic glucose uptake, experiments were conducted with seven conscious dogs using a hepatic venous catheterization technique. With the infusion of somatostatin (0.8 microg x kg(-1) x min(-1)), glucagon (0.65 ng x kg(-1) x min(-1)), and insulin (27 pmol x kg(-1) x min(-1)), arterial glucose levels could be maintained at 8 mmol/l by adjusting the intravenous glucose infusion (G(inf)) according to the following three periods: 1) peripheral glucose infusion period (PE), G(inf) alone; 2) portal glucose infusion period (PO), G(inf) plus constant glucose infusion into the portal vein (GIR(PV), 55.6 micromol x kg(-1) x min(-1)); 3) portal and brain glucose infusion period (PO+CNS), G(inf) and GIR(PV) plus additional glucose infusion into the unilateral carotid and vertebral arteries to abolish the positive glucose gradient between HPS and CNS. Arterial plasma glucose levels were clamped during the three periods (8.1 +/- 0.1, PE; 8.2 +/- 0.1, PO; 8.2 +/- 0.1 mmol/l, PO+CNS). During PO, when a positive glucose gradient was promoted between HPS and CNS, the net hepatic glucose balance (NHGB) determined by the difference between hepatic glucose inflow and outflow was significantly lower than that of PE (-41.5 +/- 5.3, PO vs. -7.5 +/- 3.4 micromol x kg(-1) x min(-1), PE; P < 0.01). However, this decrease in the NHGB significantly increased during PO+CNS, when the glucose gradient between HPS and CNS was minimized, compared with PO (-21.7 +/- 3.2 micromol x kg(-1) x min(-1), P < 0.05). We conclude that a positive glucose gradient between HPS and CNS is an important regulatory factor of hepatic glucose uptake, but other factors also play important roles because minimizing the glucose gradient between HPS and CNS diminished the net hepatic glucose uptake by 50%.

Animals↗
PubMed1996

Effect of nonpeptide motilin agonist EM523 on release of gut and pancreatic hormones in conscious dogs.

BACKGROUND & AIMS: EM523, a nonpeptide motilin agonist, is being developed for clinical use to improve delayed gastric emptying. The aim of this study was to examine the effect of EM523 on endogenous release of gut and pancreatic hormones in conscious dogs. METHODS: Motility of the gastrointestinal tract was monitored using force transducers. Blood concentrations of gut and pancreatic hormones were measured using a specific radioimmunoassay. EM523 (3 micrograms/kg) or normal saline (5 mL) was given during the phase I period of the interdigestive state. RESULTS: A single injection of EM523 always induced phase III-like contractions in the intact gastric antrum and was accompanied by significant (P < 0.01) release of motilin, pancreatic polypeptide, and insulin; glucagon, gastrin, cholecystokinin, and secretin were not released by EM523. The significant release of these hormones was suppressed by pretreatment with atropine and completely eliminated by a 5-hydroxytryptamine 3 receptor antagonist and truncal vagotomy. CONCLUSIONS: The findings suggest that EM523 stimulates the release of pancreatic polypeptide, insulin, and motilin by activating the cholinergic parasympathetic nerve system, finally stimulating the endocrine pancreas through vagally cholinergic muscarinic receptors in the pancreatic islets. The participation of 5-hydroxytryptamine 3 receptors in this system is strongly suggested by the results.

Animals↗
PubMed1995

Involvement of intracellular calcium ions in the release of the fluorescent dye calcein by cholinergic and alpha-adrenergic agonists from rat parotid acinar cells.

Effects of cholinergic and adrenergic agonists on the secretion of the fluorescent dye calcein were examined to clarify the involvement of calcium ions in the secretion of calcein from acinar cells dispersed from the rat parotid gland. Addition of carbachol (CCh) and noradrenalin (NA), but not isoproterenol (IPR), enhanced the net release of calcein from acinar cells during the subsequent 10 min in a dose range from 10(-8) M to 10(-6) M. The net release of calcein reached a maximum 7 min after the addition of CCh. The release of calcein was suppressed by the simultaneous additions of atropine with CCh, or phenoxybenzamine with NA. Addition of CCh induced a sustained dose-dependent increase in the intracellular levels of calcium ions, ([Ca2+]i). Addition of NA at 10(-6) M increased [Ca2+]i. Phenoxybenzamine completely inhibited the NA-induced increase, but propranolol did not. The removal of extracellular calcium ions did not influence the release of calcein induced by 10(-6) M CCh, but it abolished the sustained increase in [Ca2+]i. The transient increase in [Ca2+]i induced by CCh was observed in the absence of extracellular calcium ions. A calcium ion chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) inhibited the CCh-induced release of calcein. The calcium ionophore, A23187 (2.5 x 10(-6) M), but not 10(-3) M dibutyryl cAMP, evoked the release of calcein. It also increased [Ca2+]i. Removal of extracellular calcium ions suppressed the A23187-induced release of calcein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Different localizations of 21 and 27 kDa gap-junction proteins in rat salivary glands.

Antibodies against 21 and 27 kDa gap-junction proteins from rat liver were used to examine the identification and localization of gap-junction proteins in rat salivary glands. Acinar cells of the submandibular glands and parotid glands stained well for the 27 kDa gap junction protein and less intensely for the 21 kDa protein. Acinar cells of the sublingual glands were stained heavily for the 27 kDa gap junction protein and stained well for 21 kDa gap junction protein. No 27 kDa protein was observed in the ducts of the salivary glands. The 21 kDa gap-junction protein was distributed in some of the intercalated ducts in the parotid and submandibular glands. Immunoblotting of an extract of parotid glands with antibodies against 21 and 27 kDa gap-junction proteins revealed the presence of 21 and 27 kDa proteins in the parotid glands. It is concluded that the 27 kDa gap-junction protein is distributed as a major component of the gap junctions in the acinar cells of all the salivary glands; the 21 kDa protein is localized as a minor component in the acinar cells and some portions of the intercalated ducts in the salivary glands. It is possible that these gap-junction proteins might contribute to the regulation of function of the salivary glands.

Animals↗
PubMed1995

Stimulatory mechanism of EM523-induced contractions in postprandial stomach of conscious dogs.

BACKGROUND & AIMS: EM523, a motilin agonist, is intended to be used as a gastroprokinetic during the postprandial period, but the mechanism(s) by which EM523 stimulates postprandial contractions in the stomach has not been studied before. The aim of this study was to examine the mechanism of contraction-stimulating activity by EM523 in fed dogs. METHODS: Contractile activity in the gastric antrum of 5 dogs was monitored using a long-term implanted force transducer and measured by integrating the area under the curve. Test materials were continuously infused or injected intravenously. RESULTS: EM523 (1-30 micrograms/kg) induced a dose-dependent increase in fed-type contractions. EM523-induced contractile activity was partially inhibited by atropine, hexamethonium, dopamine, 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, and substance P antagonist. Atropine-resistant and EM523-induced contractions were further inhibited by 5-HT3 receptor antagonist and substance P antagonist, and the combined use of the two antagonists completely eliminated the atropine-resistant and EM523-induced contractions. CONCLUSIONS: EM523-induced contractions in the fed stomach are quite different from phase III contractions in the fasted state and are mediated partially through the cholinergic pathway. The noncholinergic pathway involves 5-HT3 and neurokinin 1 receptors.

Animals↗
PubMed1995

Insulin resistance in essential hypertensive patients with impaired glucose tolerance.

This study evaluated insulin secretion and insulin sensitivity in 17 non-obese hypertensive patients (aged 45.6 +/- 2.2 years, body mass index 24.0 +/- 0.5 kg/m2, mean +/- S.E.M.) with (n = 8) and without glucose intolerance (n = 9) and compared the results with those of 16 age-matched non-obese normotensive subjects with (n = 7) and without glucose intolerance (n = 9). The hypertensive patients without glucose intolerance showed a significantly lower insulin-mediated glucose disposal and a compensating increase in second-phase insulin secretion compared with normotensives without glucose intolerance. In hypertensives with glucose intolerance, insulin-mediated glucose disposal was significantly lower and second-phase insulin secretion was comparable to that in normotensives without glucose intolerance. After 3 months of angiotensin-converting enzyme (ACE) inhibition with oral administration of delapril, blood pressure was significantly reduced in the hypertensives with glucose intolerance (n = 9). The insulin-mediated glucose disposal significantly (P < 0.01) recovered from 6.0 +/- 0.81 to 8.0 +/- 0.71 mg/kg per min. The second-phase insulin secretion tended to be lower (but not significantly) but insulin clearance increased from 15.4 +/- 0.85 to 19.1 +/- 1.42 ml/min (P < 0.05). These data show that in hypertensive patients without glucose intolerance insulin resistance might compensatorily augment second-phase insulin secretion and lead to hyperinsulinemia. In hypertensives with glucose intolerance, insulin resistance might induce postprandial hyperglycemia, which leads to hyperinsulinemia because of second phase insulin secretion at a level similar to that of normotensives.

Administration, Oral↗