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M Shiota

Publications and source records attributed to M Shiota.

At least 55 records · Page 3Linked to original sources
PubMed1998

Determination of adenosine and deoxyadenosine in urine by high-performance liquid chromatography with column switching.

The means of measurement of adenosine and deoxyadenosine in urine was developed by separating adenosine and deoxyadenosine from other compounds using high-performance liquid chromatography with column switchings. This method is simple and convenient since no pretreatment of the urine is needed. Using this method, it could be demonstrated that urinary adenosine was higher in an adenosine deaminase (ADA) deficient patient who had a bone marrow transplant treatment (1.97 micromol/mmol creatinine) and in a heterozygote who had a markedly low erythrocyte ADA activity (1% of control ADA activity) (1.33 micromol/mmol creatinine) as compared to normal subjects (0.22+/-0.09 micromol/mmol creatinine, n=11). It was also noted that urinary deoxyadenosine was below the detection limits in the ADA-deficient bone marrow transplant patient, but it was detected in the heterozygote (3.7 micromol/mmol creatinine). Furthermore, it was also demonstrated that a fructose infusion increased the urinary concentration of adenosine from 0.21+/-0.03 to 2.66+/-1.21 micromol/mmol creatinine in five normal subjects.

Adenosine↗
PubMed1998

MICA allele typing of HLA-B27 positive Japanese patients with seronegative spondylarthropathies and healthy individuals: differential linkage disequilibrium with HLA-B27 subtypes.

OBJECTIVE: To examine whether MICA (major histocompatibility complex [MHC] class I-related chain gene A) confers additional susceptibility for seronegative spondylarthropathies in HLA-B27 positive Japanese individuals. METHODS: A polymerase chain reaction-single-strand conformation polymorphism method was developed, and the MICA alleles of 18 Japanese patients with ankylosing spondylitis, 1 patient with Reiter's syndrome, and 17 healthy HLA-B27 positive Japanese subjects were determined. RESULTS: Among 26 individuals with HLA-B*2704 (13 patients and 13 healthy subjects), all except 1 healthy individual were positive for MICA010, whereas all 9 HLA-B*2705 positive subjects (6 patients and 3 healthy subjects) possessed MICA007. One healthy individual with HLA-B*2711 also carried MICA010. CONCLUSION: Strong linkage disequilibrium is present between HLA-B*2704 and MICA010, as well as between HLA-B*2705 and MICA007. Although HLA-B*2704 and B*2705 are highly homologous, each subtype participates in a different MHC haplotype. Direct involvement of MICA polymorphism in the pathogenesis seems to be unlikely; however, such information will provide a useful tool for elucidating the evolutional pathway of HLA-B27 subtypes as well as the contribution of other genes within the MHC region in the pathogenesis of these diseases.

Alleles↗
PubMed1998

Endotoxin modulates arachidonic acid-induced glycogenolysis in the perfused rat liver.

Effects of endotoxin on arachidonic acid (AA)-induced hepatic glycogenolysis were examined in perfused rat liver. In normal rat liver, infusion of AA increased oxygen consumption and glucose production concurrently. In rats injected with lipopolysaccharide (LPS) 6 h before, AA increased glucose production but suppressed oxygen consumption. The changes in LPS-injected rat were abolished by a thromboxane (Tx) A2 receptor antagonist. The release of Tx B2 by AA increased after LPS-injection. These results suggest that priming of hepatic macrophage by endotoxin in vivo enhances Tx synthesis, resulting in modulating hepatic glycogenolysis.

Animals↗
PubMed1998

Modulation of platelet activating factor-induced glycogenolysis in the perfused rat liver after administration of endotoxin in vivo.

The effect of endotoxin treatment in vivo on platelet activating factor (PAF)-induced glycogenolysis was studied in the perfused rat liver. The addition of PAF (20 nM) to the perfusate increased glucose production concomitant with suppression of oxygen consumption in control rats without endotoxin treatment. At 6 h after endotoxin administration, PAF caused severe suppression of oxygen consumption, but glucose production was greatly inhibited. At 24 h after endotoxin treatment, PAF caused less suppression of oxygen consumption than the control, and glucose production was partially restored. The metabolic responses in the control rat were abolished by the simultaneous presence of cyclooxygenase- and lipoxygenase-inhibitors. Combined use of leukotriene (LT) D4- and thromboxane (Tx) A2-receptor antagonists inhibited the metabolic responses in the rat given endotoxin 6 h before. The efflux of Tx B2 during PAF-infusion decreased 24 h after endotoxin treatment, and Tx A2 receptor antagonist, but not LT D4 receptor antagonist, prevented the suppression of oxygen consumption. These results suggest that different eicosanoids are involved in PAF-induced glycogenolysis in different stages of endotoxemia, and that LT D1 may also play a role in PAF-induced glycogenolysis.

Animals↗
PubMed1998

A negative arterial-portal venous glucose gradient decreases skeletal muscle glucose uptake.

The effect of a negative arterial-portal venous (a-pv) glucose gradient on skeletal muscle and whole body nonhepatic glucose uptake was studied in 12 42-h-fasted conscious dogs. Each study consisted of a 110-min equilibration period, a 30-min baseline period, and two 120-min hyperglycemic (2-fold basal) periods (either peripheral or intraportal glucose infusion). Somatostatin was infused along with insulin (3 x basal) and glucagon (basal). Catheters were inserted 17 days before studies in the external iliac artery and hepatic, portal and common iliac veins. Blood flow was measured in liver and hindlimb using Doppler flow probes. The arterial blood glucose, arterial plasma insulin, arterial plasma glucagon, and hindlimb glucose loads were similar during peripheral and intraportal glucose infusions. The a-pv glucose gradient (in mg/dl) was 5 +/- 1 during peripheral and -18 +/- 3 during intraportal glucose infusion. The net hindlimb glucose uptakes (in mg/min) were 5.0 +/- 1.2, 20.4 +/- 4.5, and 14.8 +/- 3.2 during baseline, peripheral, and intraportal glucose infusion periods, respectively (P < 0.01, peripheral vs. intraportal); the hindlimb glucose fractional extractions (in %) were 2.8 +/- 0.4, 4.7 +/- 0.8, and 3.9 +/- 0.5 during baseline, peripheral, and intraportal glucose infusions, respectively (P < 0. 05, peripheral vs. intraportal). The net whole body nonhepatic glucose uptakes (in mg . kg-1 . min-1) were 1.6 +/- 0.1, 7.9 +/- 1.3, and 5.4 +/- 1.1 during baseline, peripheral, and intraportal glucose infusion, respectively (P < 0.05, peripheral vs. intraportal). In the liver, net glucose uptake was 70% greater during intraportal than during peripheral glucose infusion (5.8 +/- 0.7 vs. 3.4 +/- 0.4 mg . kg-1 . min-1). In conclusion, despite comparable glucose loads and insulin levels, hindlimb and whole body net nonhepatic glucose uptake decreased significantly during portal venous glucose infusion, suggesting that a negative a-pv glucose gradient leads to an inhibitory signal in nonhepatic tissues, among which skeletal muscle appears to be the most important.

Animals↗
PubMed1998

Small amounts of fructose markedly augment net hepatic glucose uptake in the conscious dog.

Fructose activates glucokinase by releasing the enzyme from its inhibitory protein in liver. To examine the importance of acute activation of glucokinase in regulating hepatic glucose uptake, the effect of intraportal infusion of a small amount of fructose on net hepatic glucose uptake (NHGU) was examined in 42 h-fasted conscious dogs. Isotopic ([3-3H] and [U-14C]glucose) and arteriovenous difference methods were used. Each study consisted of an equilibration period (-90 to -30 min), a control period (-30 to 0 min), and a hyperglycemic/hyperinsulinemic period (0-390 min). During the latter period, somatostatin (489 pmol x kg(-1) x min(-1)) was given, along with intraportal insulin (7.2 pmol x kg(-1) x min(-1)) and glucagon (0.5 ng x kg(-1) x min(-1)). In this way, the liver sinusoidal insulin level was fixed at four times basal (456 +/- 60 pmol/l), and liver sinusoidal glucagon level was kept basal (46 +/- 6 ng/l). Glucose was infused through a peripheral vein to create hyperglycemia (12.5 mmol/l plasma). Hyperglycemic hyperinsulinemia (no fructose) switched net hepatic glucose balance (micromoles per kilogram per minute) from output (11.3 +/- 1.4) to uptake (14.7 +/- 1.7) and net lactate balance (micromoles per kilogram per minute) from uptake (6.5 +/- 2.1) to output (4.4 +/- 1.5). Fructose was infused intraportally at a rate of 1.7, 3.3, or 6.7 micromol x kg(-1) x min(-1), starting at 120, 210, or 300 min, respectively. In the three periods, portal blood fructose increased from <6 to 113 +/- 14, 209 +/- 29, and 426 +/- 62 micromol/l, and net hepatic fructose uptake increased from 0.03 +/- 0.01 to 1.3 +/- 0.4, 2.3 +/- 0.7, and 5.1 +/- 0.6 micromol x kg(-1) x min(-1), respectively. NHGU increased to 41 +/- 3, 54 +/- 5, and 69 +/- 8 micromol x kg(-1) x min(-1), respectively, and net hepatic lactate output increased to 11.0 +/- 3.2, 15.3 +/- 2.7, and 22.4 +/- 2.8 micromol x kg(-1) x min(-1) in the three fructose periods, respectively. The amount of [3H]glucose incorporated into glycogen was equivalent to 69 +/- 3% of [3H]glucose taken up by the liver. These data suggest that glucokinase translocation within the hepatocyte is a major determinant of hepatic glucose uptake by the dog in vivo.

Animals↗
PubMed1998

[The occlusal force distribution on the dental arch restored with implants in uni-lateral molars missing].

The object of this study was to discuss the occlusal force distribution on the dental arch before and after wearing implant-supported prostheses. The occlusal force was measured on four patients missing uni-lateral molars restored with 14 dental implants. The occlusal force distribution was represented as the occlusal force bearing rate (B.R.) which is the percentage of occlusal force on each portion to the total occlusal force. B.R. of the implant portion, of the non-implant side molar portion and of the anterior portion were calculated on four patients. B.R. of the premolar implant portion and of the molar implant portion were calculated on two patients. The pressure sensitive sheets and the image scanner (Dental Prescale 50H type R and Occluzer FPD 703, Fuji Photo Film Co.) were used in this study. The results were as follows: 1. The corresponding occlusal force was also born with the implant portion. Therefore, the total occlusal force increased, and the occlusal force distribution was extended to the same degree as the natural dentition after wearing the implant-supported prostheses. 2. The occlusal force and B.R. on the molar implant portion were considerably large regardless of wearing premolar implants. 3. The occlusal force and B.R. on the most distal implant in any molar portion were almost constant. These results suggested that the implant restoration should be useful for recovering occlusal functions, and that the most distal implant on the dental arch should have the sufficient bearing potential.

Adult↗
PubMed1998

[Diagnosis for dental implant using computed tomography and precise implantation using modified stent].

The diagnosis of jaw bones using X-ray computerized tomography is effective to decide the method of implantation, the position of the implant, and the direction for the insertion of the implant. However, it is difficult to apply anatomical information to the superstructures of implants, as well as to prepare implant sockets at the proper site by using an ordinary surgical stent. This would affect the effectiveness of the X-ray computerized tomography considerably. The X-ray computerized tomography with a diagnostic stent has been used in our clinic. CT multiplaner reconstruction images with radiopaque markers are useful to examine the adaptability of implant and to determine an appropriate site of implantation for an ideal prosthesis. Moreover, the diagnostic stent is modified to the surgical stent by drilling guide holes to reproduce a precise direction for inserting implant. By applying this stent, it is possible to reproduce the optimal site and direction for the placement of implant. In this report, two cases, which were treated with diagnosis and the placement of implants by using this technique, were studied. One was a case of overdenture and the other was that of upper anterior prostheses. In both cases, precise implantation was achieved by using this technique.

Adult↗
PubMed1998

[A case of learning-disabled child with a white matter lesion in the left parietal lobe].

We reported a learning-disabled boy, 7-year-old and right handedness, who was similar to developmental Gerstmann syndrome. Dyscalcuria, right-left disorientation, dysgraphia and finger agnosia were correlated with his sequential disorder which was clearly presented by Kaufman Assessment Battery for Children. In this case, a small infarcted lesion was found in the white matter near the left semioval center on MRI. Hypoperfusion of left parietal lobe was also detected by SPECT. The hemisphere dominant in language was assumed to be on the left side by dichotic listening test. We suggested that left parietal lesion was associated with his higher cortical dysfunction.

Brain Diseases↗
PubMed1997

Effects of increased glucokinase gene copy number on glucose homeostasis and hepatic glucose metabolism.

The relationship between glucokinase (GK) gene copy number and glucose homeostasis was studied in transgenic mice with additional copies of the entire GK gene locus (Niswender, K. D., Postic, C., Jetton, T. L., Bennett, B. D., Piston, D. W., Efrat, S., and Magnuson, M. A. (1997) J. Biol. Chem. 272, 22564-22569). The plasma glucose concentration was reduced by 25 +/- 3% and 37 +/- 4% in mice with one or two extra copies of the gene locus, respectively. The basis for the hypoglycemic phenotype was determined using metabolic tracer techniques in chronically cannulated, conscious mice with one extra GK gene copy. Under basal conditions (6-h fasted) transgenic mice had a lower blood glucose concentration (-12 +/- 1%) and a slightly higher glucose turnover rate (+8 +/- 3%), resulting in a significantly higher glucose clearance rate (+21 +/- 2%). Plasma insulin levels were not different, suggesting that increased glucose clearance was due to augmented hepatic, not islet, GK gene expression. Under hyperglycemic clamp conditions the transgenic mice had glucose turnover and clearance rates similar to the controls, but showed a lower plasma insulin response (-48 +/- 5%). Net hepatic glycogen synthesis was markedly elevated (+360%), whereas skeletal muscle glycogen synthesis was decreased (-40%). These results indicate that increased GK gene dosage leads to increased hepatic glucose metabolism and, consequently, a lower plasma glucose concentration. Increased insulin secretion was not observed, even though the transgene is expressed in islets, because hypoglycemia causes a down-regulation in islet GK content (Niswender, K. D., Postic, C., Jetton, T. L., Bennett, B. D., Piston, D. W., Efrat, S., and Magnuson, M. A. (1997) J. Biol. Chem. 272, in press).

Animals↗
PubMed1997

Type-II collagen gene expression is transiently upregulated in experimentally induced degeneration of rabbit intervertebral disc.

To clarify phenotypic alterations of intervertebral disc cells during the repair process, we cloned partial type-II collagen cDNA from rabbits and analyzed the level of expression of type-II collagen mRNA in disc degeneration. An animal model was created by surgical denucleation of rabbit intervertebral discs through an extraperitoneal approach. Eight animals each from an experimental and a control group were killed at 2, 4, 8, or 16 weeks postoperatively, and the disc samples were used for this study. Round chondrocyte-like cells that filled the herniated space showed intense signal of type-II collagen mRNA and significant pericellular immunostaining of type-II collagen but no clear staining of type-I collagen. Northern blot analysis revealed that the expression of type-II collagen mRNA of the repair disc cells was transiently increased at 4 weeks postoperatively. The cells were able to change their morphology in response to mechanical stimulation by surgical denucleation and to induce a significant increase in the gene expression of type-II collagen at an early phase of disc degeneration. The present results indicate the transient enhancement of repair activity in the degenerative process of injured fibrocartilage.

Animals↗
PubMed1997

Acute effect of troglitazone on glucose metabolism in the absence or presence of insulin in perfused rat hindlimb.

Troglitazone (CS-045) is a new type of antidiabetic agent that decreases plasma glucose by enhancing insulin action in insulin-resistant diabetic animals and non-insulin-dependent diabetes mellitus (NIDDM) patients. To examine the direct effect of troglitazone on glucose metabolism and insulin action in skeletal muscle, we infused troglitazone solution into perfused rat hindlimbs in the presence of 6 mmol/L glucose and in the absence or presence of insulin. In the absence of insulin, even 50 mumol/L troglitazone did not elicit glucose uptake. Troglitazone did increase lactate and pyruvate release at concentrations of 20 mumol/L and higher; however, it decreased the ratio of lactate to pyruvate (L/P ratio) and increased oxygen consumption at concentrations higher than 5 and 20 mumol/L, respectively. In hindlimb muscle, 20 mumol/L troglitazone decreased glycogen content without changing fructose 2,6-bisphosphate (F2,6P2) content in the absence of insulin. Insulin infusion with 250 microU/mL obtained half-maximal effects, causing a 2.8-fold increase in glucose uptake and a 1.5-fold increase in lactate and pyruvate release. When 20 mumol/L troglitazone was infused for 30 minutes together with 250 microU/mL insulin, insulin-induced glucose uptake significantly increased 30 minutes after troglitazone infusion, and this increase was further augmented after withdrawal of troglitazone. In insulin plus troglitazone infusion at 30 minutes after troglitazone removal, glycogen content in hindlimb muscle was significantly decreased compared with that obtained with insulin infusion alone. In summary, in the absence of insulin, troglitazone does not elicit glucose uptake, but causes an increase in glycolysis accompanied by a decrease in muscle glycogen content and L/P ratio and an increase in oxygen consumption. In the presence of insulin, troglitazone increases insulin-induced glucose uptake, and this increase is further augmented after troglitazone removal. Addition of troglitazone to insulin infusion decreased the glycogen content in hindlimb muscle. This decrease in muscle glycogen content may trigger an enhancement of insulin-induced glucose uptake similar to that observed during muscle contraction or epinephrine treatment.

Animals↗
PubMed1997

Mechanisms of central motor reorganization in pediatric hemiplegic patients.

Twenty hemiplegic patients were studied with transcranial magnetic stimulation (TMS). Motor evoked potentials (MEPs) of the biceps brachii (BB) and the abductor pollicis brevis muscles (APB) were recorded on both sides simultaneously. TMS was carried out with an 8-shaped coil over different scalp positions in the intact hemisphere. Bilateral MEPs of BB were elicited in patients with later childhood lesions as well as early lesion, but those of APB were only elicited in the latter (up to 2 years). In patients with prenatal or birth lesion on BB and in all patients on APB, cortical maps of MEP amplitude of paretic and non-paretic sides showed similar distributions. There were no remarkable differences in mean latency between both sides, and correlation coefficients of MEP amplitude between both sides were high in these patients. In patients with postnatal lesion on BB, MEP maps of both sides showed different distributions, ipsilateral MEP latencies were delayed and correlation coefficients were low. We suspect that ipsilateral MEPs after early lesion derive from axonal sprouting both in the proximal and the distal muscles. After postnatal lesion, other mechanisms of ipsilateral motor projection take place in the proximal muscles, but not in the distal ones.

Adolescent↗
PubMed1997

The positional distribution of dioleoyl-palmitoyl glycerol influences lymph chylomicron transport, composition and size in rats.

The effects of 1,3-dioleoyl-2-palmitoyl glycerol (OPO) on lymph chylomicron transport, composition and size in rats were investigated in comparison with 1,2-dioleoyl-3-palmitoyl glycerol (OOP). The OPO and OOP were prepared by enzymatic transesterification reactions. The concentrations of OPO and OOP in the preparations were 65.7 g/100 g, and the composition of fatty acids was similar for each. The OPO preparation contained triacylglycerols with 76.6% of the palmitic acid in the sn-2 position, whereas 100% of the oleic acid was esterified to the sn-2 position in the OOP preparation. Rats were infused with lipid emulsion containing 150 g/L of OPO or OOP via a stomach catheter. Lymph was collected through the mesenteric lymphatic trunk at 1-h intervals for 12 h. Collected lymph chylomicrons were analyzed for triacylglycerol, fatty acids, apolipoprotein A-I and particle size. The maximum transport rates of triacylglycerols in the OPO group were higher than those in the OOP group. The overall absorption of triacylglycerols, palmitic acid and oleic acid in the OPO group was also higher than that in the OOP group. In the chylomicrons, 60-70% of the fatty acids at the sn-2 position of the infused triacylglycerol was transported at the original position. The transport rates of dioleoyl-palmitoyl glycerol in the OPO group were higher than those in the OOP group. The transport rates of apolipoprotein A-I did not differ between groups, whereas the mean diameter of the chylomicrons in the OPO group was larger than that in the OOP group. These results indicate that OPO is absorbed and transported more effectively than OOP.

Animals↗
PubMed1997

Anaplastic large cell lymphoma: a distinct molecular pathologic entity: a reappraisal with special reference to p80(NPM/ALK) expression.

The p80(NPM/ALK) expression activated by the t(2;5) (p23;q35) translocation recently has been shown to play an important role in the pathogenesis of anaplastic large cell lymphoma (ALCL). However, the clinicopathologic significance of identification of p80 among ALCL cases has not been completely resolved. Difficulties also exist in the histologic and immunophenotypic identification of ALCL and Hodgkin's disease (HD) as separate processes, often complicating the clinicopathologic evaluation of and therapeutic approach to these entities. In order to clarify these issues, 67 specimens of ALCL and 63 specimens of HD (31 of the nodular-sclerosing type [NS-HD] and 32 of the mixed-cellularity type [MC-HD]) were immunostained using anti-p80 antibody and other relevant markers on paraffin sections. The clinicopathologic and immunophenotypic features were reviewed on the basis of p80 reactivity. The expression of p80 was detected in 43 of 67 cases of ALCL (64%), but none of HD. The p80+ ALCL cases constituted a very homogeneous group of tumors, characterized by the occurrence in a much younger group and relatively more favorable clinical course than the p80- ALCL, which were in keeping with the data previously reported. They showed virtually the identical immunophenotypic findings of p80+, CD30+, EMA+, CD15-, bcl-2-, and Epstein-Barr virus (EBV) with T- and null-cell phenotype, and showed the distinct morphologic features, including three cases of lymphohistiocytic/small-cell variant, as follows: the indented nuclei, often termed as reniform, embryolike, and horseshoelike; multiple, irregular, but indistinct nucleoli; and few reactive cells of eosinophils and epithelioid cells. Conversely, the 24 p80- ALCL cases, in which epithelial membrane antigen (EMA) and bcl-2 positivities were 33% and 55%, respectively, were heterogeneous and could be subdivided into five different categories, namely (a) 11 cases of HD-like ALCLs, (b) six cases of p80 common ALCL, (c) three cases of secondary ALCL, (d) two cases of primary cutaneous ALCL, and (e) two cases of primary classical ALCL that lacked p80 expression. This study clearly demonstrated that the immunohistochemical detection of p80 is of a crucial importance in delineating the biologically distinct entity of "primary classical ALCL" from various diseases that show morphologic and immunohistologic overlap, including HD and HD-like ALCL.

Adolescent↗
PubMed1997

The t(2;5)-associated p80 NPM/ALK fusion protein in nodal and cutaneous CD30+ lymphoproliferative disorders.

A high percentage of extracutaneous CD30+ anaplastic large cell lymphomas (nodal ALCL) carry a specific chromosomal translocation, t(2;5) (p23;q35), that results in abnormal expression of p80 NPM/ALK chimeric protein (p80). The protein p80 may be detected by immunohistochemistry using polyclonal (anti-p80) or monoclonal (ALK1) antibody directed against the ALK epitope. Although nodal ALCL, primary cutaneous ALCL, and lymphomatoid papulosis type A (lyp A) have similar histologic and immunohistochemical features, the expression of p80 in these cutaneous lesions has not been extensively studied. We immunostained tissues from 10 nodal ALCL, 8 primary cutaneous ALCL, 24 lyp A, and positive and negative controls using polyclonal rabbit anti-p80 and the avidin-biotin-peroxidase labeling method. Reactivity was determined by comparing staining intensity to positive controls [4 nodal ALCL with t(2;5)] and negative controls (21 non-ALCL lymphomas). Only cutaneous lesions staining positively with anti-p80 were further studied with the monoclonal antibody ALK1 and reverse transcription polymerase chain reaction (RT-PCR) for p80 messenger RNA. All positive controls (4/4), but none of the negative controls (0/21) nor lyp A (0/24), were immunoreactive for anti-p80. Sixty percent (6/10) of nodal ALCL and a single case (12%) of primary cutaneous ALCL were immunoreactive for anti-p80. In this exceptional cutaneous lesion, although we did not find NPM/ALK by RT-PCR, we detected strong expression of ALK using ALK1. We conclude that t(2;5) is rarely involved in the pathogenesis of cutaneous CD30+ lymphoproliferative disorders.

Anaplastic Lymphoma Kinase↗
PubMed1997

Inhibition of glycogenolysis enhances gluconeogenic precursor uptake by the liver of conscious dogs.

We investigated the effect of inhibiting glycogenolysis on gluconeogenesis in 18-h-fasted conscious dogs with the use of intragastric administration of BAY R 3401, a glycogen phosphorylase inhibitor. Isotopic ([3-3H]glucose and [U-14C]alanine) and arteriovenous difference methods were used to assess glucose metabolism. Each study consisted of a 100-min equilibration, a 40-min control, and two 90-min test periods. Endogenous insulin and glucagon secretions were inhibited with somatostatin (0.8 microgram.kg-1.min-1), and the two hormones were replaced intraportally (insulin: 0.25 mU.kg-1.min-1; glucagon: 0.6 ng.kg-1.min-1). Drug (10 mg/kg) or placebo was given after the control period. Insulin and glucagon were kept at basal levels in the first test period, after which glucagon infusion was increased to 2.4 ng.kg-1.min-1; BAY R 3401 decreased tracer-determined endogenous glucose production [rate of glucose production (Ra): 14 +/- 1 to 7 +/- 1 mumol.kg-1.min-1] and net hepatic glucose output (11 +/- 1 to 3 +/- 2 mumol.kg-1.min-1) during test 1. It increased the net hepatic uptake of gluconeogenic substrates from 9.0 +/- 2.0 to 11.6 +/- 0.6 mumol.kg-1.min-1. Basal glycogenolysis was decreased by drug (9.1 +/- 0.7 to 1.5 +/- 0.2 mumol glucosyl U.kg-1.min-1). Placebo had no effect on Ra or the uptake of gluconeogenic precursors by the liver. The rise in glucagon increased Ra by 22 +/- 3 and by 8 +/- 2 mumol.kg-1.min-1 (at 10 min) in placebo and drug, respectively. The rise in glucagon caused little change in the net hepatic uptake (mumol.kg-1.min-1) of gluconeogenic substrates in placebo (8.2 +/- 0.6 to 9.0 +/- 1.0) but increased it markedly (11.6 +/- 0.6 to 15.4 +/- 1.0) in drug. Glucagon increased glycogenolysis by 22.1 +/- 2.5 and by 7.8 +/- 1.6 mumol.kg-1.min-1 in placebo and drug, respectively. The amount of glycogen (mumol glucosyl U/kg) synthesized from gluconeogenic carbon was four times higher in drug (48.6 +/- 9.7) than in placebo (11.3 +/- 1.7). We conclude that BAY R 3401 caused a marked reduction in basal and glucagon-stimulated glycogenolysis. As a result of these changes, there was an increase in the net hepatic uptake of gluconeogenic precursors and in glycogen synthesis.

Analysis of Variance↗