PubMed Health⌕ Search

Biomedical subjects

M Daimon

Publications and source records attributed to M Daimon.

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

Effects of glucagon on glycogenolysis and gluconeogenesis are region-specific in periportal and perivenous hepatocytes.

It has been established, mainly by histochemical and immunohistochemical studies, that liver cells are functionally heterogeneous, with periportal hepatocytes (PPHs) being predominantly gluconeogenic and perivenous hepatocytes (PVHs) being glycolytic. We therefore investigated the region-specific functional effects of glucagon on glycogenolysis and gluconeogenesis in isolated PPHs and PVHs prepared by the digitonin-collagenase method. BB rats, a model of insulin-dependent diabetes, were used to study the region-specific heterogeneity of gluconeogenesis in the diabetic state. Although glycogen content was not different between PVHs and PPHs in rats fed the normal diet, basal glucose release was 1.37 times greater in PVHs than in PPHs (P <.05). The increase in glucose release stimulated by 0.01 to 0.1 nmol/L glucagon was 1.52 times greater in PVHs than in PPHs (P < .05), whereas no differences were seen in response to 1 to 100 nmol/L glucagon. Glucose release from gluconeogenic substrates was 1.57 times greater in the PPHs than in the PVHs of fasted normal rats (P < .05), whereas the increase in gluconeogenesis produced by glucagon was not different between PPHs and PVHs. The glucagon-binding capacity, the cAMP release, and the increase in intracellular Ca2+ stimulated by glucagon were not different between PPHs and PVHs in the fed or fasted states. Gluconeogenesis from gluconeogenic substrates was 1.52 times greater in the PPHs than in the PVHs of fasted nondiabetic BB rats (P < .05). After the development of diabetes, the gluconeogenic capacity in PVHs increased to the level observed in PPHs, but that in PPHs did not change. Thus there was no difference in gluconeogenesis between the PPHs and PVHs of diabetic BB rats. In both the PPHs and PVHs of diabetic BB rats, the 0.01 to 100 nmol/L glucagon-induced increase in gluconeogenesis was greater than that in PPHs from nondiabetic BB rats (2.30 and 3.07 times, P < .01, respectively). We conclude that PPHs and PVHs of normal rat liver express region-specific differences in their glycogenolytic and gluconeogenic responses to glucagon. In diabetic BB rats, the difference in the gluconeogenic capacity between PPHs and PVHs disappeared, whereas glucagon-induced gluconeogenesis was enhanced.

Animals↗
PubMed1998

Impaired vagus nerve-mediated control of insulin secretion in Wistar fatty rats.

It has been reported that hyperglycemia in the portal venous blood suppresses afferent activity of the hepatic branch of the vagus nerve, which in turn accelerates efferent activity of the pancreatic branch of the vagus nerve to stimulate insulin secretion. The present study examined this neural control mechanism in genetically obese diabetic male Wistar fatty (fa/fa) rats. Adult (aged 12 to 14 weeks) Wistar fatty rats were obese, hyperinsulinemic, and hyperglycemic. Young (aged 5 to 6 weeks) Wistar fatty rats were slightly obese and hyperinsulinemic, but were euglycemic compared with the lean littermates. In both adult and young lean littermates, the plasma insulin response after an intragastric glucose load (1 g/kg) was diminished by intracerebroventricular (i.c.v.) atropine methylbromide (methylatropine 10 nmol) pretreatment, and a transient increase in plasma insulin was observed after selective hepatic vagotomy, as reported in normal rats. In contrast, in both adult and young Wistar fatty rats, the plasma insulin response after an intragastric glucose load was not diminished by i.c.v. methylatropine pretreatment, and plasma insulin decreased slightly after selective hepatic vagotomy. Further, afferent discharges of the hepatic vagal branch decreased and efferent discharges of the celiac/pancreatic vagal branch increased when 10 mg glucose was infused into the portal vein in the 9-week-old lean littermates, as reported in normal rats. In 7-week-old Wistar fatty rats, afferent discharges of the hepatic vagal branch decreased but efferent discharges of the celiac/pancreatic vagal branch did not increase after intraportal glucose infusion. It is concluded that the vagus nerve-mediated regulation of insulin secretion is impaired from an early stage of life in Wistar fatty rats. Efferent discharges of the vagus nerve to the pancreas seem not to be suppressed by afferent discharges from the hepatic vagus branch, which may lead to insufficient insulin secretion in response to nutrient ingestion followed by a delayed peak. These abnormalities may thus lead to the insulin resistance and fasting hyperinsulinemia that characterize the Wistar fatty rat model.

Animals↗
PubMed1998

Hyperglycemia is a factor for an increase in serum ceruloplasmin in type 2 diabetes.

OBJECTIVE: To examine if there is a correlation between high blood glucose and serum ceruloplasmin (Cp) levels. RESEARCH DESIGN AND METHODS: Serum Cp levels were measured in 637 patients with type 2 diabetes (all type 2 diabetes group). For the follow-up type 2 diabetes group, 161 patients who had not had any changes in their situation during the last year that are known to influence serum Cp levels were reexamined 1 year later. The control group was composed of 158 healthy individuals. Serum Cp and blood HbA1c levels were measured by radial immunodiffusion and high-performance liquid chromatography assays, respectively. RESULTS: Serum Cp levels in the all type 2 diabetes group were significantly higher than those in the control group (P < 0.0001), although the serum Cp levels did not correlate with the blood HbA1c levels in the all type 2 diabetes group (r = 0.055, P = 0.351). Then we evaluated those factors (delta-log Cp and delta-HbA1c) in the follow-up type 2 diabetes group to minimize changes from the genetic differences and to exclude any known factors influencing serum Cp levels. This indicated that the delta-HbA1c had a positive correlation to the delta-log Cp (r = 0.304, P < 0.0001). CONCLUSIONS: A persistent high blood glucose (namely HbA1c) is associated with an increase in serum Cp levels over 1 year.

Adult↗
PubMed1998

Three-dimensional conformation of the epitopes of human superoxide dismutase-2 recognized by antibody against HIV-1p17.

We have previously reported that antibodies against HIV-1p17 protein cross-react with human superoxide dismutase-2 (SOD-2). To identify and characterize the epitopes of human SOD-2 recognized by anti-HIV-1p17 antibody, we synthesized several peptide fragments of human SOD-2 and found that the antibody did not bind to the LQPALK hexapeptide which is contained in both HIV-1p17 and human SOD-2. Instead, this antibody bound to four peptides which contain amino acid sequences similar, but not identical, to the known epitopes of HIV-1p17. These peptides have two features in three-dimensional (3-D) conformation: two protruded carbohydrate side chains on the peptide chain or a concave structure in the molecule. It is suggested that the antibody does not strictly recognize the amino acid sequence itself, but may recognize these 3-D conformations.

Animals↗
PubMed1998

A novel autoantibody in paraneoplastic sensory-dominant neuropathy reacts with brain-type creatine kinase.

We have previously reported on a novel autoantibody in a patient with paraneoplastic sensory-dominant neuropathy. This autoantibody immunostains the rat primary sensory system and reacts with a 47 kDa protein on immunoblotting. Here, we report on the isolation from rat spinal cord of a molecule that is recognized by this autoantibody. By ammonium sulfate cut and gel filtration, affinity and ion exchange chromatographies, the immunoreactive protein was purified to homogeneity and identified as brain-type creatine kinase (B-CK). Our study revealed that the autoantibody of the patient reacted with B-CK in the primary sensory system.

Amino Acid Sequence↗
PubMed1997

Antibodies to the HIV-1 p17 protein cross-react with human superoxide dismutase-2.

Antibodies reacting with the gag protein p17 of the human immunodeficiency virus type 1 (HIV-1) can occasionally be found in the serum of non-HIV-1-infected individuals. Conversely, anti-p17 antibodies can also react with human tissues from non-infected individuals. Here we report on the isolation from human liver of a molecule that is immunoreactive with anti-p17 antibodies. This molecule was purified to homogeneity and identified as superoxide dismutase-2 (manganese type SOD). Both human SOD-2 and HIV-1 p17 contain the LQPALK hexapeptide which may serve as a common antigenic determinant. This study indicates that human SOD-2 is a target for anti-p17 antibodies and suggests that HIV-1-negative individuals may possess SOD-2 auto-antibodies that cross-react with HIV-1 p17.

Amino Acid Sequence↗
PubMed1997

Identification of a human cDNA homologue to the Drosophila translocation protein 1 (Dtrp1).

In yeast, several integral membrane proteins such as Sec61p, Sec62p and Sec63p have been reported as the components involved in protein translocation across and into the endoplasmic reticulum (ER) membrane. Among them, the homologues of Sec61p have been found both in bacterias and mammals, whereas those of Sec62p or Sec63p have not. So, Sec61p seem to be the evolutionary conserved component, while Sec62p and Sec63p may not. To date, no homologues of Sec62p have been found in mammals yet. Here, we report a novel human cDNA, HTP1 (for human translocation protein 1), that encodes a protein of 399 amino acids that is 36.3% identical (64.6% similar) to Drosophila homologue of Sec62p, Drosophila translocation protein 1 (Dtrpl). Northern blot analysis showed two HTP1 transcripts of about 2.8 and 5.5 kb, which were expressed concomitantly in various human tissues such as heart, brain, placenta, liver and pancreas.

Amino Acid Sequence↗
PubMed1997

A novel missense mutation in exon 4 of the human coproporphyrinogen oxidase gene in two patients with hereditary coproporphyria.

Hereditary coproporphyria (HCP) is an autosomal dominant disease characterized by a deficiency of coproporphyrinogen oxidase. To date, four mutations of the gene have been reported. We report here another mutation in two Japanese families with HCP, which was revealed by analysis of polymerase chain reaction (PCR)-amplified DNA fragments of the gene by a direct-sequencing method. A point mutation, G to A, was found in exon 4 of the gene at position 538 of the cDNA from the reported putative translation initiation codon ATG. This mutation results in a glycine to arginine substitution at amino acid 180. Two carriers in the family were successfully diagnosed by detecting the mutation using restriction analysis of the PCR products.

Adult↗
PubMed1997

Islet changes in hereditary ceruloplasmin deficiency.

Diabetes mellitus (DM) is the important initial symptom of hereditary ceruloplasmin deficiency (HCD). We examined the pancreas of an autopsy case of HCD and revealed a marked reduction in insulin-containing cells in the islets despite no massive iron deposition, degeneration, nor necrosis. Non-insulin-containing cells in the islets had glucagon or somatostatin. This study indicates that DM in HCD results from depletion of insulin cells and this depletion does not seem to be caused by the direct effect of iron deposition. The present observation suggests that the defect of the ceruloplasmin gene may influence the population of islet cells.

Ceruloplasmin↗
PubMed1997

Increased epinephrine-induced cAMP response in severely diabetic BB/W rat liver.

The effect of prolonged diabetes on epinephrine-induced adenosine 3',5'-monophosphate (cAMP) response in the liver was examined in diabetes-prone BB/W rats. Basal and 1 microM epinephrine-induced cAMP release from isolated perfused liver was similar in non-diabetic and diabetic BB/W rats with preserved adipose tissue. In adipose tissue-absent diabetic rats losing intra- and retro-peritoneal adipose tissue completely, both basal and 1 microM epinephrine-induced cAMP release from the liver were enhanced (P<0.01, each case). Plasma epinephrine and norepinephrine were similar in non-diabetic, adipose tissue-preserved and -absent diabetic BB/W rats. The plasma free thyroxine level was similar in non-diabetic and adipose tissue-preserved diabetic BB/W rats, but was lower in adipose tissue-absent diabetic BB/W rats than in non-diabetic rats (P<0.01), but the frequency of lymphocytic thyroiditis was similar in these three groups, although plasma corticosterone was lower in adipose tissue-preserved diabetic BB/W rats (P<0.05) and the lowest in adipose tissue-absent diabetic BB/W rats (P<0.01). Lymphocytic infiltration was not observed in the adrenal or pituitary glands in any group. Plasma total protein and albumin were low in adipose tissue-absent diabetic BB/W rats (P<0.01, each case). In adipose tissue-absent diabetic BB/W rats, liver dysfunction and hepatomegaly, but no apparent histological change in the liver, were observed. Plasma glucose was higher (P<0.01) and plasma insulin lower (P<0.05) in adipose tissue-absent diabetic BB/W rats than in adipose tissue-preserved diabetic BB/W rats. In conclusion, epinephrine-induced cAMP response in the liver was enhanced only in adipose tissue-absent diabetic BB/W rats. Denervation supersensitivity was not likely to be responsible for the enhanced beta-adrenergic response. The observed reductions in plasma thyroxine and corticosterone seemed to result from severe diabetes. Although the severity of diabetes can vary continuously, severe diabetes with loss of adipose tissue appeared to cause significant changes in the metabolism and enhanced beta-adrenergic response in the liver.

Alanine Transaminase↗
PubMed1996

Family study of acute intermittent porphyria and hereditary coproporphyria in Niigata and Akita Prefectures, Japan.

Simple screening tests, urinary porphobilinogen (PBG) for acute intermittent porphyria (AIP) and fecal coproporphyrin for hereditary coproporphyria (HCP), were performed in a family study of AIP and HCP. Urinary PBG was positive in 93 of 211 members of 10 AIP families, but was negative in 568 of 572 controls. Fecal coproporphyrin was positive in 54 of 108 members of 10 HCP families, but was negative in 188 controls. A dominant inheritance was assumed by a chi-square test and Weinberg segregation ratio. Worsening factors around puberty were suggested by the onset age and cumulative percentage of genetically loaded cases. Sex-related expression of symptoms was also inferred by a higher incidence of both porphyrias in females than in males. Fitness and penetrance of both porphyrias were good. An l-triiodothyronine loading test was the most useful for the detection of masked carriers of AIP. In conclusion, AIP and HCP in Japan show a dominant inheritance with sex-related metabolic and clinical manifestations.

Adolescent↗
PubMed1996

Hereditary caeruloplasmin deficiency: clinicopathological study of a patient.

A 58 year old patient with dementia, oral dyskinesia, and diabetes mellitus is described. He had an undetectable concentration of serum caeruloplasmin, as an autosomal recessive trait. Brain MRI disclosed a pronounced hypointensity in the bilateral putamina, caudate, and dentate nuclei on both T1 and T2 weighted images. Pathological findings were mainly in those regions of the brain and consisted of neuronal cell loss with gliosis, heavy iron deposition, and spheroids. Visceral organs also had iron deposition, especially severe in the liver and pancreas. The present patient and other recorded cases constitute a clinicopathological entity of hereditary caeruloplasmin deficiency, different from Wilson's disease.

Brain↗
PubMed1996

Functional localization of glucose transporter 2 in rat liver.

Heterogeneity of zonal hepatocytes is important to elicit specific liver function. We investigated the distribution of glucose transporter 2 (GLUT-2) in normal rat liver by immunostaining and Northern blot analysis. GLUT-2 stained by immunohistochemistry was distributed predominantly in the periportal hepatocytes and gradually thinned towards the perivenous zone. Ultrastructural immunostaining of GLUT-2 showed that it was localized on microvilli of the sinusoidal plasma membrane of hepatocytes but not on the basolateral plasma membrane. Consistent with the distribution of GLUT-2 protein, the level of GLUT-2 mRNA in periportal hepatocytes was 1.9-fold higher than in perivenous hepatocytes selectively isolated by the differential isolation technique. In addition, the mRNA level of phosphoenolpyruvate carboxykinase, one of the key enzymes of gluconeogenesis, was also twofold higher in the periportal hepatocytes. These results suggest that GLUT-2 contributes to the functional difference between periportal and perivenous hepatocytes in glucose metabolism of the liver.

Animals↗
PubMed1995

A nonsense mutation of the ceruloplasmin gene in hereditary ceruloplasmin deficiency with diabetes mellitus.

A novel mutation of the ceruloplasmin (Cp) gene was found in a patient with hereditary ceruloplasmin deficiency (HCD) with diabetes mellitus (DM). The patient had been treated for DM for about 13 years, and then his illness was diagnosed as HCD. One year later, he was found dead in his home. A decrease in insulin-immunostained cells was observed in the islets of the patient's pancreas tissue, which accounted for his DM. The polymerase chain reaction (PCR)-direct sequencing analysis of the Cp gene of his daughter revealed a novel point mutation, G to A, at nucleotide 2630 in exon 15. This mutation changes the Trp858 codon (TGG) to a stop codon (TAG) (nonsense mutation). PCR-restriction analysis for the mutation revealed that the patient as well as his daughter was a heterozygote for the mutation, indicating that the patient was a compound heterozygote.

Amino Acid Sequence↗
PubMed1995

Fine structure of the human ceruloplasmin gene.

We characterized the genomic region corresponding to the human ceruloplasmin cDNA previously reported. Using PCR-direct sequencing methods, we determined precise intron/exon boundaries and intron-exon composition of the gene in the region. The gene region spanned about 50 kb and was composed of 19 exons and 18 introns. The lengths of exons and introns range from 107 to over 267 bp and from 0.44 to 10.0 kb, respectively. The translation initiation codon and the termination codon were located in exons 1 and 19, respectively. The nucleotide sequences of the introns were also determined in the region around the intron/exon boundaries for 24-220 bp. All the sequences around the intron/exon boundaries were consistent with the 5' and 3' consensus sequences for splice junctions of transcribed genes. Putative lariat sequences were identified between -17 and -42 nucleotides from the 3' splice junction for all 18 introns.

Alternative Splicing↗
PubMed1995

Response of truncated glucagon-like peptide-1 and gastric inhibitory polypeptide to glucose ingestion in non-insulin dependent diabetes mellitus. Effect of sulfonylurea therapy.

Gastric inhibitory polypeptide (tGIP) and truncated glucagon like peptide-1 (GLP-1) are potent gastrointestinal insulinotropic factors (incretin), are most released after a meal or ingestion of glucose in man and animals. To investigate whether sulfonylurea (SU) affects the secretion of incretin, the modulation of plasma GIP and tGLP-1 levels following glucose ingestion in non-insulin-dependent diabetic type 2 patients with or without SU therapy was studied. A 75-G oral glucose tolerance test (OGTT) was carried out on 9 healthy subjects (controls) and 18 patients with non-obese type 2, 9 of whom were treated by diet alone (NIDDM-diet) and the other 9 with SU (glibenclamide 2.5 mg or gliclazide 40 mg) once a day (NIDDM-SU). Plasma GIP was measured by radioimmunoassay (RIA) with R65 antibody, and GLP-1 was measured by RIA with N-terminal-directed antiserum R1043 (GLP-1NT) and C-terminal-directed antiserum R2337 (GLP-1CT). Following OGTT, plasma glucose, GIP, GLP-1NT, and GLP-1CT in type 2 patients increased more markedly than in controls, despite the lower response of insulin. However, there were no significant differences in plasma levels of these peptides between the NIDDM-diet and NIDDM-SU groups. Therefore, it is unlikely that SU is involved in the high response of GIP and GLP-1s to OGTT in type 2 patients.

Administration, Oral↗