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H Manaka

Publications and source records attributed to H Manaka.

At least 19 recordsLinked to original sources
PubMed2001

Hormone-specific combinations of isoforms of adenylyl cyclase and phosphodiesterase in the rat liver.

Since many isoforms of adenylyl cyclase and adenosine 3', 5'-monophosphate (cAMP) phosphodiesterase have been cloned, it is likely that receptors of each hormone have a specific combination of these isoforms. Types I, III and VIII adenylyl cyclases are reported to be stimulated by Ca(2+)-calmodulin, type I phosphodiesterase by Ca(2+)-calmodulin, but types IV and VII (cAMP-specific) phosphodiesterases by Co2+. In the present study, we examined different effects of Ca2+ and Co2+ on hormone-induced cAMP response in the isolated perfused rat liver.The removal of Ca2+ from the perfusion medium (0 mM CaCl(2 ) + 0.5 mM EGTA) did not affect glucagon (0.1 nM)-responsive cAMP but reduced secretin (1 nM)-, vasoactive intestinal polypeptide (VIP, 1-10 nM)- and forskolin (1 microM)-responsive cAMP considerably. The addition of 1 mM CoCl2 reduced glucagon- and secretin-responsive cAMP considerably, forskolin-responsive cAMP partly, did not affect 1 nM VIP-responsive cAMP, but enhanced 10 nM VIP-responsive cAMP. Forskolin- and VIP-responsive cAMP was greater in the combination (0 mM CaCl(2) + 0.5 mM EGTA + 3 mM CoCl2) than in the Ca(2+)-free perfusion alone. These results suggest that secretin, VIP1 and VIP2 receptors are linked to Ca(2+)-calmodulin-sensitive adenylyl cyclase; glucagon receptor to Ca(2+)-calmodulin-insensitive adenylyl cyclase; VIP1 receptor to Ca(2+)-calmodulin-dependent phosphodiesterase; glucagon, secretin and VIP2 receptors to cAMP-specific phosphodiesterase, respectively, in the rat liver.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Insulin inhibits glucagon-induced glycogenolysis in perivenous hepatocytes specifically.

Hepatocytes form the hepatic acinus as the unit of microcirculation. Following the bloodstream, at least 2 different zones can be discerned: the periportal and perivenous zones. Two types of hepatocytes, periportal hepatocytes (PPHs) and perivenous hepatocytes (PVHs), have been thought to be functionally heterogeneous, with PPHs being predominantly gluconeogenic and PVHs being glycolytic. We therefore investigated the region-specific functional effects of insulin on glycogen synthesis, glycolysis, glycogenolysis, and gluconeogenesis in isolated PPHs and PVHs prepared by using the digitonin-collagenase method. Glycogen synthesis from 5 to 20 mmol/L glucose did not differ between the PPHs and PVHs of fed rats during 60 minutes of incubation. Lactate release induced by 5 to 20 mmol/L glucose was 3 times greater from PVHs than from PPHs (P <.01). The addition of insulin did not accelerate either glycogen synthesis or lactate release during 60 minutes of incubation. Insulin did not inhibit glucose release from gluconeogenic substrates with or without 0.2 nmol/L glucagon in either the PPHs or the PVHs of fasting rats. Insulin antagonized the 0.1 nmol/L glucagon-induced increase in glucose release from the PVHs of fed rats during 30 minutes of incubation (to 56.1% +/- 7.2%, P <.01) but not that from the PPHs (to 81.8% +/- 7.3%, P =.10). Thus the antagonizing effect was greater in PVHs than in PPHs (P <.01). Insulin binding did not differ between the PPHs and PVHs of fed rats. It was confirmed that PVHs are actually glycolytic. An acute metabolic effect of insulin was observed only in antagonizing glucagon-induced glycogenolysis in PVHs specifically. The specific effect of insulin on PVHs might depend on the differences in intracellular characteristics between PPHs and PVHs rather than hormone binding.

Animals↗
PubMed2001

Genotype Arg/Arg, but not Trp/Arg, of the Trp64Arg polymorphism of the beta(3)-adrenergic receptor is associated with type 2 diabetes and obesity in a large Japanese sample.

OBJECTIVE: Despite a large number of studies, no association of the Trp64Arg polymorphism of the beta(3)-adrenergic receptor gene with obesity and type 2 diabetes has yet to be clearly elucidated. We examined the associations in a large population-based sample. RESEARCH DESIGN AND METHODS: A total of 1,685 subjects (935 women and 750 men, aged 58.7 +/- 12.4 years) from a cohort population (n = 3,706) of the Funagata Diabetes Study were divided into three groups according to genotypes: Trp/Trp (n = 1,155), Trp/Arg (n = 486), and Arg/Arg (n = 44). Glucose tolerance was diagnosed according to the 1985 World Health Organization criteria. Subjects who had a BMI > or =30 kg/m(2) were considered obese. Associations with the traits related to obesity, diabetes, hypertension, and dyslipidemia were also examined. The chi(2) test and analysis of variance were used for the association studies and to assess the differences in the traits' values, respectively. RESULTS: More subjects with genotype Arg/Arg were obese and had diabetes (13.6% for each) than those with genotype Trp/Trp (3.29%, P < 0.001; and 4.16%, P = 0.007, respectively) or genotype Trp/Arg (2.06%, P < 0.001; and 5.97%, P = 0.051, respectively). No significant differences in the frequencies of occurrence of these conditions were observed between genotypes Trp/Arg and Trp/Trp. Traits related to obesity, such as percent body fat (28.82 +/- 7.95 vs. 25.93 +/- 7.21, P = 0.038) and BMI (25.07 +/- 3.84 vs. 23.63 +/- 3.18, P = 0.018), were higher in the genotype Arg/Arg than in the genotype Trp/Trp groups. CONCLUSIONS: Genotype Arg/Arg, but not Trp/Arg, of the beta(3)-adrenergic receptor was associated with both obesity and type 2 diabetes in a large Japanese sample.

Aged↗
PubMed2000

Impaired neural regulation of insulin secretion related to the leptin receptor gene mutation in Wistar fatty rats.

The Wistar fatty (WF) rat is a model of obese Type 2 diabetes mellitus (DM). These rats were bred by crossing Zucker fatty (ZF) and Wistar-Kyoto (WKY) rats. A homo-allelic leptin receptor gene mutation has been reported in ZF rats. We report here how these genetic factors contribute to plasma insulin regulation. The fasting plasma insulin levels were higher in WKY and Wistar lean (WL) rats than in Zucker lean (ZL) rats (p<0.05). The levels in WF and ZF rats were higher than in their respective lean littermates, WL and ZL rats (p<0.05). After intragastric glucose load, the plasma insulin increase was reduced upon pretreatment by intracerebroventricular (i. c.v.) methylatropine (an antagonist of the cholinergic receptor) injection in WL rats (p<0.05) but not in WF rats. Plasma glucagon-like peptide-1 (GLP-1) response to intragastric glucose load was not affected by methylatropine. After selective hepatic-vagotomy, plasma insulin levels increased in wild-type ZL rats (p<0.05). This increase was not observed in heterozygote ZL rats. Surprisingly, this response of plasma insulin was not shown in wild-type WL and WKY rats. ZF and WF rats did show a prominent decrease in insulin response (p<0.05). These results indicate that the genetic factor in ZF rats is associated with impaired vagal nerve-mediated control of insulin secretion. The genetic factor in WKY rats may diminish sensitivity to the vagal information of insulin release and contribute to insulin resistance. Therefore, we conclude that the presence of both genetic factors in a homo-allelic state is important to the development of DM in WF rats.

Animals↗
PubMed2000

Thiazolidinediones exert different effects on insulin resistance between dexamethasone-treated rats and wistar fatty rats.

We determined the in vivo effects of thiazolidinediones on insulin resistance induced by dexamethasone (Dx), as well as that observed in Wistar fatty (WF) rats, using glucose clamp technique to measure glucose uptake (Gu) and percent suppression of hepatic glucose output (HGOsup) to evaluate insulin resistance. Male Wistar rats were treated with Dx (0.5 mg/kg/day) for 7 days. Pioglitazone (P) or troglitazone (T) was coadministered orally for the same period at 10 and 200 mg/kg/day, respectively. Two, 5 and 20 mU/kg/min. of insulin infusion rates (IIR) were used. The Gu levels at clamp steady-state at IIR20 in rats treated with Dx (16.4 +/- 4.7 mg/kg/min.) were significantly lower than those in control rats (36.3 +/- 2.4). The Gu levels at the same IIR in rats coadminstered with P (19.6 +/- 3.2) and T (21.3 +/- 6.3) were slightly but significantly higher than that in rat treated with Dx. HGOsup at IIR5 in control rats (97.5 +/- 6.2%) was decreased by Dx treatment (52.1+/- 31.3). This decrease was slightly but significantly ameliorated by addition of T (78.3 +/- 12.2). The Gu levels at IIR20 in WF rats (6.6 +/- 0.9) were decreased significantly from that in lean littermates of WF (WL) rats (25.8 +/- 2.1). This attenuation of Gu increase was completely ameliorated with administration of P (20.9+/-2.8) or T (22.2+/-3.9). The HGOsup at IIR20 in WF rats (17.4 +/- 11.2) was significantly decreased from that in WL rats. Administration of P or T ameliorated this decrease completely. These results indicate that Dx induces insulin resistance by mechanisms different from those in WF rat, hence thiazolidinedione administration can be only partially useful to treat insulin resistance induced by Dx.

Animals↗
PubMed2000

Increase in serum ceruloplasmin with aging is not observed in type 2 diabetes.

Changes of serum ceruloplasmin (Cp) levels have been reported in many conditions including diabetes mellitus (DM), in which the serum Cp levels were increased. In this study, we have examined the influence of aging on serum Cp levels in normal individuals and in individuals with DM. Serum Cp levels were measured in 85 outpatients with type 2 diabetes (type 2 DM group) as well as in 71 healthy individuals (control group). All patients recruited for this study were negative for the glutamic acid decarboxylase (GAD) antibody. The subjects were sub-grouped based on their ages (<55 and 55 < or =). The serum Cp levels in the control group increased significantly with aging (r=0.325, p<0.0055), while levels in the type 2 DM group did not (r=0.091, p=0.4079). The levels in the type 2 DM group (<55) were significantly higher than those in the control group (<55) (p = 0.0029), while the Cp levels in the type 2 DM group (55 < or =) were not different from those in the control group (55 < or =) (p=0.4187). An age-related increase of serum Cp levels was observed in normal individuals, but this change was not observed in type 2 DM patients since serum Cp levels in type 2 DM patients of all ages were similar to the levels in normal elderly individuals.

Adult↗
PubMed1999

Acute intermittent porphyria with central pontine myelinolysis and cortical laminar necrosis.

Acute intermittent porphyria (AIP) is an autosomal-dominant disease caused by a deficiency of porphobilinogen (PBG) deaminase. Patients with AIP present with neurological syndromes such as autonomic neuropathy, peripheral axonal neuropathy or central nervous system dysfunction. We report serial MRI of a patient with AIP who had cortical and subcortical cerebral changes. A 29-year-old woman with a 6-month history of AIP had an attack with severe hyponatraemia and generalised convulsions, treated with haem arginate and supportive therapy. MRI showed central pontine and extrapontine myelinolysis and cortical laminar necrosis. These are not common in AIP, but are likely to have been caused by rapid correction of hyponatraemia and by vasospasm, which could be induced by AIP.

Adult↗
PubMed1999

Evaluating the reported prevalence of type 2 diabetes mellitus by the Oguni diabetes registry using a two-sample method of capture-recapture.

BACKGROUND: Capture-recapture methods have been widely employed in the study of wildlife populations and have recently been applied to count various human diseases and conditions. We have estimated the prevalence of type 2 diabetes mellitus by adjusting for the degree of undercount using a two-sample model of capture-recapture among men and women aged 50-69 in Oguni town, Japan. METHODS: Oguni town diabetes registry data were utilized as the first source. In the registry, only those who had experienced fasting plasma glucose of > or = 7.8 mmol/l (140 mg/dl) or 2 h plasma glucose after a 75 g oral glucose tolerance test (OGTT) of > or = 11.1 mmol/l (200 mg/dl) were counted as having diabetes. A second source was a sample study selecting 200 men and 200 women aged 50-69 randomly, which was conducted in August 1991. A 75 g OGTT was done in the morning. The 1985 World Health Organization criteria were used to classify the diabetes status of the participants. A two-sample model of capture-recapture methods was employed to estimate the total number of cases of diabetes and determine the ascertainment rates of the registry. RESULTS: The prevalence estimated by the diabetes registry was 7.1%. The prevalence from the sample study was 8.8% with a participation rate of 74%. Estimated prevalence employing the capture-recapture method was 13.1%. The ascertainment rate of the registry was 53.8%. CONCLUSIONS: Little is known about the prevalence of type 2 diabetes in local areas in Japan, the US and the world. Capture-recapture methods are likely to provide a means to accurately assess the prevalence of diabetes.

Aged↗
PubMed1999

Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study.

OBJECTIVE: To determine whether the new category of impaired fasting glucose (IFG) recently proposed by the Expert Committee of the American Diabetes Association is a risk factor for cardiovascular disease. RESEARCH DESIGN AND METHODS: Death certificates and residence transfer documents from the cohort population consisting of participants of the diabetes prevalence study in Funagata, Yamagata prefecture, Japan, 1990-1992, were analyzed up through the end of 1996. First, the cohort population was classified into three groups: normal glucose tolerance (NGT) (n = 2,016), impaired glucose tolerance (IGT) (n = 382), and diabetic (n = 253). Then the same population was reclassified into normal fasting glucose (NFG), IFG, and diabetic. The cumulative survival rates among the groups were compared using the classical life-table method, and age-adjusted analyses, the person-year method, and Cox's proportional hazard model were adopted. RESULTS: At the end of seven observed years, the cumulative survival rates from cardiovascular disease of IGT and diabetes were 0.962 and 0.954, respectively, both significantly lower than that of NGT (0.988). The Cox's proportional hazard model analysis showed that the hazard ratio of IGT to NGT on death from cardiovascular disease was 2.219 (95% CI 1.076-4.577). However, the cumulative survival rate of IFG from cardiovascular disease was 0.977, not significantly lower than that of NFG (0.985). The Cox's hazard ratio of IFG to NFG on death from cardiovascular disease was 1.136 (0.345-3.734), which was not significant either. CONCLUSIONS: IGT was a risk factor for cardiovascular disease, but IFG was not.

Aged↗
PubMed1999

[Endovascular surgery for untreated ruptured aneurysm with symptomatic vasospasm].

It is difficult to treat ruptured aneurysms with symptomatic vasospasm. Although direct surgery for such cases is associated with poor outcomes, conservative therapy has the risk of both rerupture and infarction. In two cases of ruptured aneurysms with symptomatic vasospasm, we performed aneurysmal coil embolization with Guglielmi electrodetatchable coils (GDC). At the same time we performed percutaneous transluminal angioplasty (PTA) with papaverine infusion. In both cases, rerupture did not occur and PTA was effective angiographically. A good outcome was achieved in case 1. However, broad cerebral infarction occurred in case 2, in which the patient had shown severe symptomatic vasospasm on admission. In advanced cases, such as in case 2, the outcome is poor. The aneurysm may not be able to be approached before PTA because of severe vasospasm. In such cases, PTA must be performed carefully to avoid aneurysmal rerupture. Intraarterial papaverine infusion is safer than PTA for severe spasm in distal vessels. However the efficacy of papaverine is known to be transient in many cases. It is often difficult to determine the exact relationship between branches and the aneurysm in the presence of vasospasm. In such cases, we recommend that the rupture point be packed and that the aneurysmal neck remain unpacked. After vasospasm is cured and good general condition has been recovered, direct surgery can be performed. In summary, endovascular surgery is an effective option for treatment of ruptured aneurysm with symptomatic vasospasm.

Aged↗
PubMed1998

Relative contribution of Ca2+-dependent mechanism in glucagon-induced glucose output from the liver.

Divalent cations are known to affect the activity of the cAMP-generating system. By observing the effects of the addition of cobalt (Co2+) and the depletion of calcium (Ca2+), this study tried to determine the relative contribution of Ca2+-dependent mechanism in glucagon-induced glucose output from the isolated perfused rat liver. Co2+ (1 mM) completely suppressed glucose and cAMP output induced by 0.1 nM glucagon and partly suppressed those induced by 1 to 10 nM glucagon. Co2+ (1-5 mM) did not inhibit 125I-labeled glucagon binding to hepatic cell membrane. Phenylephrine- or angiotensin II-induced glucose output was not affected by 1 mM Co2+. Co2+ (1 mM) inhibited a glucagon-induced increase in [Ca2+]i in isolated rat hepatocytes but did not inhibit a phenylephrine-induced increase in [Ca2+]i. The removal of Ca2+ from the perfusion medium impaired phenylephrine- or angiotensin II-induced glucose output, but did not impair glucagon-induced glucose output. When glucagon-induced cAMP production was inhibited by Co2+, the glucose output produced by 1 to 10 nM glucagon was impaired further in the Ca2+-free perfusion. Addition of 0.1 mM IBMX increased the glucose output produced by 1 nM glucagon but did not increase that produced by 10 nM glucagon in the Co2+-containing Ca2+-free perfusion. These results suggest that Co2+ inhibits the glucagon-responsive adenylyl cyclase system directly, resulting in impaired glucose output. Glucagon increases [Ca2+]i through a mechanism different from that of phenylephrine. Glucagon (0.01-10 nM)-induced glucose output from the liver is derived mainly through a cAMP-dependent mechanism. Only when glucagon-induced cAMP production was inhibited by Co2+ was the Ca2+ dependency observed in high concentrations (>/=1 nM) of glucagon-induced glucose output, and it approximated 30% of the glucose output produced by 10 nM glucagon.

Angiotensin II↗
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

Intradural extension of mucocele complicating frontoethmoid sinus osteoma: case report.

BACKGROUND: Osteomas of the paranasal sinus are often asymptomatic and are sometimes complicated by mucoceles, but intradural extension of such a mucocele has rarely been reported. CASE DESCRIPTION: This 67-year-old man with complaint of headache was diagnosed as having an intradural extension of a mucocele complicating an osteoma of the frontoethmoid sinus. A right frontobasal craniotomy was performed and a mucocele in the frontal sinus extending into the frontal lobe through two dural defects and the osteoma was removed completely. The patient was successfully treated without recurrence. CONCLUSION: The importance of radical surgery for such lesions and the relationship between osteomas and mucoceles are discussed.

Aged↗
PubMed1998

Sequential changes in CGRP-like immunoreactivity in NIDDM model Otsuka Long-Evans Tokushima Fatty (OLETF) rat pancreatic islets.

We describe the changes in B cells and calcitonin gene-related peptide (CGRP)-like immunoreactivity in the pancreatic islets of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of human non-insulin-dependent diabetes mellitus (NIDDM). In the OLETF rat pancreatic islets, CGRP immunoreactivity was seen in the nerve fibers with multiple varicosities and in endocrine cells that were identical to somatostatin-containing cells, but some somatostatin-immunoreactive cells lacked CGRP immunoreactivity. In the OLETF rats, plasma insulin levels were significantly higher than in the control rats (Long-Evans Tokushima Otsuka; LETO) only at 7 weeks of age. From 7 through 32 weeks of age, OLETF rats had a greater B-cell area than LETO rats. The length of CGRP-immunoreactive nerve fibers per area and the numbers of CGRP-immunoreactive cells per area did not differ between the groups at 7 weeks of age. After 16 weeks of age, both of these CGRP parameters in the OLETF rats became increasingly higher than in the LETO rats. These results suggest that CGRP is a B-cell growth factor and probably an inhibitory factor for insulin secretion.

Animals↗