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H Ohnuma

Publications and source records attributed to H Ohnuma.

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

Characterization of an inhibitory effect of pioglitazone on balloon-injured vascular smooth muscle cell growth.

This study investigates whether pioglitazone could suppress an atherogenic process such as balloon-injured carotid intimal thickening and the proliferation of vascular smooth muscle cells (VSMC). We first examined the effect of pioglitazone to determine whether it could suppress intimal thickening induced by balloon catheterization in Sprague-Dawley rats. After 14 days postcatheterization in the left common carotid artery, the neointimal layers were completely occupied by proliferated VSMC, and the area ratio of neointima to media treated with 10 mg/kg/d of pioglitazone was significantly decreased to 57%. Next, we evaluated the effect of pioglitazone on the proliferation of rat cultured VSMC. Piogliotazone dose-dependently decreased the values of DNA synthesis, total cellular protein content, phosphorylations of extracellular signal-regulated protein kinase 1/2 and mitogen-activated protein kinase kinase 1/2, and proliferative cell nuclear antigen in VSMC. Pioglitazone also inhibited the phosphorylation of Pyk2. We conclude that pioglitazone itself could be effective for suppressing the growth of VSMC and consequent carotid intimal thickening.

Animals↗
PubMed2001

The first large-scale nucleic acid amplification testing (NAT) of donated blood using multiplex reagent for simultaneous detection of HBV, HCV, and HIV-1 and significance of NAT for HBV.

The first nationwide nucleic acid amplification testing (NAT) for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus type 1 (HIV-1) of voluntarily donated blood after serological pre-screening and before release of cellular components and plasma for fractionation was implemented by the Japanese Red Cross Blood Transfusion Services. From February 1, 2000 to April 30, 2001, specimens from 6,805,010 units of serologically negative donation were screened in minipools of 50 samples within 24 hr after blood donation by NAT using multiplex HBV/HCV/HIV-1 reagent for blood transfusion including short shelf-life platelets. Among them, 112 HBV DNA-positives, 25 HCV RNA positives and 4 HIV-1 RNA positives were screened out and we could prevent transfusion of these NAT positive units. Subtypes/genotypes of HBV DNA, adr/C, adw/A, adw/B, adw/C, ayr/C and ayw/D were found and adr/C was predominant. A total of 61.6 % of them (69/112) were negative by overnight EIA. Sixth three of HBV NAT-positive samples carried virus loads less than 10(4) copies/mL and 92.1 % of them (58/63) were negative by overnight EIA. The virus growth curves of HBV in 6 cases obtained by retrospective and prospective follow-up study showed exponential straight lines in the early stage of serological window periods and the log times of HBV growth (10 fold increase) in serological window period were between 4.6 and 7.6 days. NAT screening with highly sensitive reagents in pool of specimens is useful to exclude blood units with low level of HBV and HBV mutants from blood transfusion.

Blood Donors↗
PubMed2001

Platelet-derived growth factor BB-induced p38 mitogen-activated protein kinase activation causes cell growth, but not apoptosis, in vascular smooth muscle cells.

The aim of this experiment was to examine the regulation of p38 mitogen-activated protein (MAP) kinase by platelet-derived growth factor (PDGF)-BB and its biological effects on rat cultured vascular smooth muscle cells (VSMCs). VSMCs were obtained from aortae of male Wistar rats by the media explant technique. After being stimulated by PDGF-BB with or without the p38 MAP kinase-specific inhibitor, SB-203580, the cells were solubilized, and the levels of phosphorylated p38 MAP kinase were examined by immunoblot analysis. The amounts of DNA synthesis and content were measured by using [3H]-thymidine and Hoechst-33258 dye, respectively. The detection of apoptotic cells was evaluated by the TUNEL method. PDGF-BB could phosphorylate p38 MAP kinase dose-dependently, and the phosphorylation was specifically inhibited by SB-203580 in a dose-dependent manner. However, PDGF-BB did not affect the protein level of p38 MAP kinase. Both [3H]-thymidine incorporation and total cellular DNA content were increased by PDGF-BB, and these elevations were prevented by SB-203580. In contrast, PDGF-BB-stimulated VSMCs did not show apoptotic change in spite of the presence or absence of SB-203580. These results established that PDGF-BB activated p38 MAP kinase and subsequently regulated cell growth in VSMCs, providing a molecular mechanism by which p38 MAP kinase can cause the development of cardiovascular diseases, including atherosclerosis.

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

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↗
PubMed2000

A novel mutation of the ceruloplasmin gene in a patient with heteroallelic ceruloplasmin gene mutation (HypoCPGM).

We found a novel missense mutation in the ceruloplasmin (Cp) gene in a patient with the heteroallelic Cp gene mutation (HypoCPGM). The patient was a 72-year-old woman who came to our hospital with a 1-year history of postural tremor of the hands. The diagnosis was made based on serum Cp and copper readings which were about half the normal levels, as well as MRI tests of her brain which showed characteristics for hereditary ceruloplasmin deficiency (HCD), known to be caused by the homoallelic Cp gene mutation. Polymerase chain reaction (PCR)-direct sequencing analysis of the Cp gene of the patient revealed a novel point mutation, A to T, at nucleotide position 82 in Exon 1. This mutation changes the Ile28 codon (ATT) to a Phe codon (TTT) (missense mutation). PCR-restriction analysis with restriction enzyme Tsp EI for the mutation revealed that both the patient and her son were heterozygotes for the mutation.

Aged↗
PubMed1999

Intracellular behavior of rabies virus matrix protein (M) is determined by the viral glycoprotein (G).

To investigate the nature and intracellular behavior of the matrix (M) protein of an avirulent strain (HEP-Flury) of rabies virus, we cloned and sequenced the cDNA of the protein. Using expression vectors pZIP-NeoSV(X)1 and pCDM8, the cDNA was transfected to animal cells (BHK-21 and COS-7) with or without coexpression of viral glycoprotein (G). When M protein alone was expressed in the cells, it displayed homogeneous distribution in the whole cell including the nucleus. In contrast, coexpression with G protein resulted in the abolishment of nuclear distribution of M antigen, and both of the antigens displayed a colocalized distribution in the cell, especially at the cellular membrane as seen in the virus-infected cells, while the distribution of G antigen was not affected by coexpressed M antigen. Immunoprecipitation studies revealed that M protein was coprecipitated with G protein by anti-G antibody, and vice versa, although cross-linking with dithiobis(succinimidyl propionate) was necessary for coprecipitation because of their easier dissociation in the presence of sodium deoxycholate. These results suggest that M protein intimately associates with G protein, which may affect or regulate the behavior (e.g., intracellular localization) of M protein. Studies with deletion mutants of M protein indicate that an internal region around the amino acids from 115 to 151 is essential for the M protein to preserve its binding ability to G protein.

Amino Acid Sequence↗
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

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↗
PubMed1997

A monoclonal antibody against a hepatitis B e antigen epitope borne by six amino acids encoded by the precore region.

Hepatitis B e antigen (HBeAg) polypeptide in the circulation (p17e) is composed of ten amino acids (aa) coded for by the precore region and 149 aa by the core gene of hepatitis B virus. A monoclonal antibody (Y0583A) was raised against the N-terminal ten amino acids (SKLCLGWLWG) encoded by the precore region. The binding of Y0583A with a panel of 203 decapeptides on multipins, which covered the precursor of HBeAg polypeptide made of 212 aa shifting by one aa, recognized an epitope sequenced LGWLWG representing the C-terminal six aa coded for by the precore region. This HBeAg epitope was not readily accessible on HBeAg in serum, but it became exposed and bound with Y0583A by treatment with 0.2 N NaOH. Using Y0583A, an enzyme-linked immunosorbent assay was developed for specific determination of HBeAg. The test sample was incubated with the monoclonal antibody to an HBeAg determinant encoded by the core gene (904) that had been immobilized on a solid support. Captured HBeAg was treated with 0.2 N NaOH, neutralized and released into the fluid phase. The reactant was then tested for a sandwich between monoclonal antibody (C33) to the C-terminus of the HBeAg polypeptide immobilized on a solid support and Y0583A labeled with horseradish peroxidase.

Amino Acid Sequence↗
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

Intracerebroventricular injection of methylatropine suppresses insulin response to oral glucose load in rats.

Hepatic glucoreceptor-vagal afferent inputs to the central nervous system and pancreatic vagal efferent stimuli are important for insulin secretion. In the present study, we examined the effect of intracerebroventricular (i.c.v.) injection of atropine methyl bromide (methylatropine) on the insulin response following glucose ingestion in rats. When rats were injected with methylatropine i.c.v., the plasma glucose concentration increased, the insulin response reduced, and glucagon-like peptide-1 (7-36) amide (tGLP-1) was unchanged following an oral glucose load, compared with the controls. The plasma insulin response following an intravenous glucose load was not affected by i.c.v. or intraperitoneal injection of methylatropine. A transient increase in plasma insulin after selective hepatic vagotomy was inhibited by i.c.v. injection of methylatropine. Arterial blood pressure or pulse rate was not changed by i.c.v. injection of methylatropine. These results show that the central nervous system plays an important role in the vagal control of the insulin response to glucose ingestion. In rats, for the insulin response soon after glucose ingestion (early phase insulin response), direct neural control (hepatic vagal afferent-central nervous system-pancreatic vagal efferent) of the islet B cells seems more important than the intestinal insulinotropic hormone, tGLP-1.

Administration, Oral↗