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Biomedical subjects

K Fujiyama

Publications and source records attributed to K Fujiyama.

At least 55 records · Page 3Linked to original sources
PubMed1993

Possible role of the adrenergic mechanism in gastric inhibitory polypeptide- and glucagon-like peptide-1 (7-36) amide-induced insulin release in the rat.

Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1(7-36) amide (GLP-1) are thought to be the most probable candidates for incretin. However, the precise mechanism of incretin effect is unclear. In the present study, to elucidate the possible role of the autonomic nervous system in incretin effect, the effects of atropine, propranolol, metoprolol, and phentolamine on GIP- or GLP-1-induced insulin release were investigated in the rat. The GIP-induced (2 or 20 micrograms) insulin release was partly inhibited by propranolol pretreatment (0.5 mg/kg subcutaneously [SC]), and GLP-1-induced (2 or 20 micrograms) insulin release was partly inhibited by propranolol or metoprolol (35 mg/kg SC). These results suggest that a beta-adrenergic mechanism may be involved in the incretin effect, probably through a modulating effect on GIP- or GLP-1-induced insulin secretion.

Animals↗
PubMed1993

Cloning, sequence analysis and expression in Escherichia coli of a gene encoding an alginate lyase from Pseudomonas sp. OS-ALG-9.

A gene (aly) encoding alginate lyase (ALY; EC 4.2.2.3) was isolated from a library constructed with the cosmid vector pHC79 and Sau3AI-digested genomic DNA of Pseudomonas sp. OS-ALG-9. Successive subcloning of the aly-containing cosmid enabled us to locate the gene on a 2.3 kb HpaI fragment. Nucleotide sequencing of this fragment revealed a single open reading frame (ORF) of 1365 bp. The directly determined N-terminal amino acid sequence of the ALY protein purified from Pseudomonas sp. OS-ALG-9 was found in the amino acid sequence deduced from this ORF between nucleotides 282 and 366. Expression of aly was induced by IPTG in Escherichia coli and leakage of the enzyme into the extracellular milieu was significantly enhanced by addition of glycine to the growth medium. The ALY enzyme had a greater specificity for the homopolymer of mannuronate than for that of guluronate.

Amino Acid Sequence↗
PubMed1993

Correlation between blood pressure and plasma insulin in acromegaly.

OBJECTIVES: The aims of this study were to determine the possible role of hyperinsulinaemia in the increase in blood pressure in acromegalic patients. DESIGN: After an overnight fast, blood samples were obtained at 0. 30, 60, 120 and 180 min after 75 g glucose ingestion, and plasma growth hormone (GH) and plasma insulin (IRI) were measured by radioimmunoassay. The blood pressure was measured at 10.00 hours for 3 days in a supine position. SUBJECTS: Nineteen (nine women and 10 men) untreated acromegalic patients, aged 25-69 years. RESULTS: There were no significant correlations between mean blood pressure (MBP; diastolic+one-third pulse pressure) and basal GH, sum of plasma GH at 0, 30, 60, 120 and 180 min or basal IRI. However, significant correlation was observed between MBP and IRI at 120 min (r = 0.57, P < 0.02) or sum of plasma IRI at 0, 30, 60, 120 and 180 min) (r = 0.58, P < 0.02). CONCLUSIONS: We conclude that hyperinsulinaemia may be involved in an increase in blood pressure in active acromegalics.

Acromegaly↗
PubMed1993

Hepatic extraction and hepatic action of insulin, glucagon, and epinephrine in bivascularly perfused rat liver.

Using a bivascularly perfused rat liver, we investigated the hepatic extraction and hepatic action on glucose output of insulin, glucagon, and epinephrine. The liver was perfused for 70 min without recirculation via the portal vein and hepatic artery (3.0 ml/(min.g liver) from portal vein and 1.0 ml/(min.g liver) from celiac artery). Low and high concentration of insulin, glucagon, or epinephrine (450 and 4,500 pM, 21.5 and 215 pM, or 410 and 4,100 pM, respectively) was added to the perfusing medium via portal vein (P-liver), via celiac artery (H-liver), or via portal vein and celiac artery (H-P-liver). Hepatic extraction of insulin, glucagon, or epinephrine was not significantly different among H- (56 +/- 9 and 21 +/- 5%, 31 +/- 7 and 24 +/- 6%, or 22 +/- 8 and 17 +/- 5%), P- (50 +/- 10 and 23 +/- 6%, 32 +/- 9 and 23 +/- 7%, or 22 +/- 9 and 18 +/- 6%), and H-P-liver (55 +/- 11 and 24 +/- 6%, 30 +/- 9 and 26 +/- 8%, or 20 +/- 9 and 17 +/- 6%). Glucagon- or epinephrine-induced increase in glucose output was also similar in H- (245 +/- 47 and 498 +/- 82 mumol/30 min, or 112 +/- 21 and 215 +/- 38 mumol/30 min), P- (258 +/- 51 and 512 +/- 95 mumol/30 min, or 128 +/- 20 and 220 +/- 36 mumol/30 min), and H-P-liver (263 +/- 58 and 515 +/- 94 mumol/30 min, or 129 +/- 22 and 225 +/- 39 mumol/30 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Uptake of ketone bodies in perfused hindquarter and kidney of starved, thyrotoxic, and diabetic rats.

To elucidate the peripheral disposal of ketone bodies in hyperketonemia accompanied with starvation, hyperthyroidism, or diabetes mellitus, the uptake of acetoacetic acid (AcAc) and beta-hydroxybutyrate (BOHB) was investigated in the perfused hindquarter and kidney of starved, thyrotoxic, and diabetic rats. Thyrotoxicity was induced by daily subcutaneous injection of thyroxine (100 micrograms/kg/day) for 7 days, and diabetes mellitus was induced by intraperitoneal streptozotocin (50 mg/kg) injection. Plasma concentration of AcAc and BOHB was significantly higher in starved, thyrotoxic, and diabetic rats than in controls. The hindquarter or kidney of rats was perfused with synthetic medium containing 0.2 or 1.5 mM AcAc or BOHB for 30 min at a flow rate of 0.5 ml/g muscle wt/min or 3.2-3.5 ml/kidney/min, respectively. In perfused hindquarter, the uptake of AcAc and BOHB was significantly reduced in starved and diabetic rats, but not in thyrotoxic rats. In perfused kidney, the uptake of AcAc and BOHB was not significantly different between the experimental and control rats. These results suggest that in starvation or diabetes mellitus, disposal of AcAc and BOHB was impaired in the hindquarter but not in the kidney, and that disposal of AcAc and BOHB by hindquarter and kidney was not impaired in thyrotoxic rats.

3-Hydroxybutyric Acid↗
PubMed1993

[Eradication therapy of Helicobacter pylori in gastroduodenal ulcer and its long-term course].

We investigated the efficacy of antimicrobial drugs, amoxicillin and clarithromycin that have the in vitro activity against H. pylori, and observed a long term course of ulcer after eradication. The eradication rate of combination therapy with PPI and amoxicillin showed best result (13/18: 72%). In eradicated cases, index of PAS positive substance and gastritis score in antral mucosa that is histological examination was improved, and ammonia concentration in gastric secretions decreased. The recurrent rate of ulcer in long term course after eradication was investigated, the recurrent rate of ulcer was significantly lower in H pylori eradicated cases than in H. pylori continuously positive cases. Results suggest that eradication of H. pylori may be controlled recurrence of H. pylori positive peptic ulcer.

Amoxicillin↗
PubMed1992

Molecular cloning and sequencing of an alternatively spliced form of the human thyrotropin receptor transcript.

In the present study, we report the molecular cloning and sequencing of an alternatively spliced form of the human thyrotropin receptor (hTSHR) mRNA transcript, which has previously been detected on Northern blot analysis of human thyroid cells. The smaller hTSHR cDNA, designated hTSHR cDNA-I, is approximately 1 kb in size and encodes a protein of 253 amino acids. Comparison of the nucleotide sequence of hTSHR cDNA-I with available hTSHR genomic sequence data reveals that the cDNA-I contains exons 1-8 and unidentified DNA tract, presumably an intron. Thus, the hTSHR cDNA-I encodes for the N-terminal half of the extracellular domain of the hTSHR (approximately 60%). The truncated TSHR-I may be secreted and function as a TSH binding protein.

Alternative Splicing↗
PubMed1992

Impairment of the TSH signal transduction system in human thyroid carcinoma cells.

In order to further evaluate the role of TSH in the proliferation and the differentiation of human thyroid carcinoma cells, we have analyzed the function of the TSH receptor in the established thyroid carcinoma cell lines NPA and WRO. The TSH signal transduction system in the carcinoma cells was also compared with that in normal thyroid cells. Although unresponsiveness to bovine and human TSH was demonstrated by measurement of cAMP production and [3H]thymidine incorporation after treatment of TSH, cAMP production was induced after stimulation of these cells by forskolin, cholera toxin, and isoproterenol. Specific binding to 125I-TSH was demonstrated in both NPA and WRO cells in addition to the existence of a TSH receptor mRNA and thyroglobulin mRNA species, although thyroid-specific gene expression in these cells was not regulated by TSH. These findings suggest that the unresponsiveness to TSH in these cells may be due to an abnormality of TSH receptor-G protein coupling rather than to a decreased level of TSH-receptor expression or a Gs protein abnormality.

Base Sequence↗
PubMed1992

Intraduodenal osmolality directly enhances insulin secretion in the rat.

To elucidate the direct effect of an intestinal osmolality on insulin release, we investigated the insulin response to intra-duodenal infusion of mannitol in rats. After the anesthesia with intraperitoneal pentobarbital sodium, one milliliter of mannitol solution (10% or 20%) was infused into the duodenum. Portal and femoral blood insulin concentrations significantly increased at 30, 60, and 120 min after intra-duodenal infusion of mannitol, although the blood glucose level did not change. Subcutaneous pre-administration of propranolol (0.4mg/kg) or metoprolol (25mg/kg) completely abolished this phenomenon. These results suggest that intestinal osmolality can directly enhance insulin secretion and that beta 1-adrenergic mechanism is involved in this phenomenon.

Adrenergic beta-Antagonists↗
PubMed1992

In vitro effects of glycosylated insulin in perfused liver and hindquarter in rats.

Using the perfused liver and hindquarter of the rat, the uptake of glycosylated insulin and its effect on glucose output were investigated. Insulin was glycosylated in ambient high glucose concentration, and glycosylated insulin GI80 (insulin incubated with 0.08% glucose), GI350 (incubated with 0.35% glucose), and GI1000 (incubated with 1% glucose) were prepared. The liver and hindquarter were perfused with nonglycosylated insulin (N-GI) or glycosylated insulin at a concentration of 100 or 1000 microU/ml. There were no significant differences in the fractional uptake of insulin by perfused liver and hindquarter despite glycosylation. Insulin-induced decrement in glucose output was significantly lower in the liver perfused with GI1000 than that in the liver perfused with N-GI, GI80, and GI350 at an insulin concentration of 100 microU/ml. There were no significant differences in insulin-induced decrement in glucose output between the hindquarter perfused with N-GI, GI80, GI350, and GI1000. These results suggest that when insulin (100 microU/ml) is incubated with a markedly elevated concentration of glucose (1000 mg/dl) its biological activity is reduced in the liver, but not in the hindquarter.

Animals↗
PubMed1992

Adrenergic mechanism in hyperketonemia in thyrotoxic and starved rats.

To evaluate the possible role of the adrenergic mechanism in hyperketonemia in hyperthyroidism and starvation, the plasma concentrations of FFA, acetoacetate (AcAc), and beta-hydroxybutyrate (BOHB) were measured in thyrotoxic and starved rats for 96 hours. Thyrotoxemia was induced in rats by a daily subcutaneous thyroxine (100 micrograms/kg/day) injection carried out for 7 days. Some of the thyrotoxic and starved rats were administered subcutaneous phentolamine (2 mg/kg, twice daily) or propranolol (0.1 mg/kg, twice daily). Plasma levels of FFA, AcAc, and BOHB were significantly increased in thyrotoxic and starved rats compared with the control rats. Phentolamine and propranolol administration did not alter plasma levels of FFA, AcAc, and BOHB in thyrotoxic rats. In starved rats, propranolol did not alter plasma levels of FFA, AcAc, and BOHB, however, phentolamine did increase plasma levels of FFA, AcAc, and BOHB. These results indicate that the adrenergic mechanism may not contribute to the hyperketonemia in thyrotoxic rats, but may have a slight inhibitory effect on ketogenesis in starvation probably due to alpha-antilipolytic action.

3-Hydroxybutyric Acid↗
PubMed1992

In vitro effects of glycosylated insulin and glucagon in perfused liver of the rat.

Using perfused liver of the rat, the hepatic uptake of glycosylated insulin (GI) and glucagon (GG) and its effects on hepatic glucose output were investigated. Insulin and glucagon were glycosylated in ambient high glucose concentration, and GI80 or GG80 (insulin or glucagon incubated with 0.08% glucose), GI350 or GG350 (incubated with 0.35% glucose), and GI1000 or GG1000 (incubated with 1% glucose) were prepared. The liver was perfused with the medium containing 1000 microU/ml insulin and 200 pg/ml glucagon or 200 microU/ml insulin and 1000 pg/ml glucagon. The fractional uptake of insulin or glucagon by perfused liver was not significantly altered by the glycosylation. In the liver perfused with 1000 microU/ml insulin and 200 pg/ml glucagon, glucose output was not changed by the glycosylation of the hormones, while in the liver perfused with 200 microU/ml insulin and 1000 pg/ml glucagon, GI1000 reduced its biological activity, as reflected by insulin-mediated decrease in glucose output. These results suggest that in the liver insulin incubated with markedly high concentration of glucose reduces its biological activity at a physiological concentration in the presence of high concentration of glucagon.

Animals↗
PubMed1991

Amino acid alterations essential for increasing the catalytic activity of the nylon-oligomer-degradation enzyme of Flavobacterium sp.

The structural genes of two homologous enzymes, 6-aminohexanoate-dimer hydrolase (EII; nylB) and its evolutionally related protein EII' (nylB') of Flavobacterium sp. KI72 have an open reading frame encoding a peptide of 392 amino acids, of which 47 are different, and conserved restriction sites. The specific activity of EII towards 6-aminohexanoate dimer is about 1000-fold that of EII'. Construction of various hybrid genes obtained by exchanging fragments flanked by conserved restriction sites of the two genes demonstrated that two amino acid replacements in the EII' enzyme, i.e. Gly181----Asp (EII type) and His266----Asn (EII type), enhanced the activity toward 6-aminohexanoate dimer 1000-fold.

Amidohydrolases↗
PubMed1991

Uptake of beta-hydroxybutyrate in perfused hindquarter of starved and diabetic rats.

To elucidate the peripheral ketone body uptake and the role of insulin in regulating peripheral ketone body utilization in starvation and diabetes mellitus, uptake of beta-hydroxybutyrate (BOHB) was investigated in the perfused hindquarter of starved (72 hour) or streptozotocin-induced (65 mg/kg, intraperitoneally) diabetic rats. Blood concentration of BOHB was significantly higher in diabetic (1,380 +/- 250 mumol/L) and starved (1,229 +/- 245 mumol/L) rats than in controls (104 +/- 8 mumol/L). The hindquarter was perfused with synthetic medium at a flow rate of 0.5 mL/g muscle weight/min. BOHB was added to the medium at a concentration of 0.1, 0.5, 2, or 10 mmol/L, and insulin was added at a concentration of 20, 100, or 500 microU/mL. In the hindquarter perfused with 0.1, 0.5, 2, or 10 mmol/L BOHB, fractional uptake of BOHB in the absence or presence of insulin was significantly lower in diabetic and starved rats than in controls. The addition of 100 or 500 microU/mL insulin significantly increased BOHB uptake in the perfused hindquarter of control rats; however, insulin addition did not significantly increase BOHB uptake in the perfused hindquarter of starved and diabetic rats. These results suggest that BOHB uptake is markedly reduced in the perfused hindquarter of starved and diabetic rats, and that physiological dose of insulin stimulates BOHB uptake in control rats, but not in starved and diabetic rats.

3-Hydroxybutyric Acid↗
PubMed1991

Serum lipid and apolipoprotein levels in non-hypertensive lean NIDDM patients.

To determine the possible role of a glycaemic control in lipid metabolism in non-insulin-dependent diabetes mellitus (NIDDM) patients, serum lipid and apolipoprotein levels were measured in well-controlled and poorly controlled lean NIDDM without proteinuria and hypertension. A sample of 96 lean NIDDM patients (body mass index less than 25 kg m-2 in men and less than 27 kg m-2 in women) were divided into two groups: group I, where the HbA1c concentration had been less than 6% for the previous 3 months, and group II, where the HbA1c concentration had been greater than 8% for the previous 3 months. Serum total cholesterol, triglyceride, and HDL-cholesterol levels showed no significant differences between groups I and II. Furthermore, serum levels of apolipoproteins AI, AII, B, CII, CIII, and E did not differ significantly between groups I and II. These results suggest that glycaemic control did not influence lipid metabolism in lean NIDDM patients.

Adult↗
PubMed1991

Stimulating effect of thyroid hormone on insulin-like growth factor I release and synthesis by perfused rat liver.

The direct effect of thyroid hormone on insulin-like growth factor I (IGF-I) release and synthesis was investigated in perfused rat liver. Physiological doses (from 50 to 1000 ng/dl) of 3,5,3'-triiodothyronine administration in the perfusing medium increased IGF-I release and concentration in the perfused liver in a dose dependent manner. While physiological doses (from 2 to 10 micrograms/dl) of thyroxine did not affect the release and synthesis of IGF-I in the perfused liver. These results suggest that 3,5,3'-triiodothyronine, but not thyroxine, directly enhances the release and synthesis of IGF-I in a dose dependent manner in the rat liver.

Animals↗