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1.
Nat Commun ; 14(1): 1960, 2023 Apr 07.
Article in English | MEDLINE | ID: mdl-37029139

ABSTRACT

The quest for entangled spin excitations has stimulated intense research on frustrated magnetic systems. For almost two decades, the triangular-lattice Mott insulator κ-(BEDT-TTF)2Cu2(CN)3 has been one of the hottest candidates for a gapless quantum spin liquid with itinerant spinons. Very recently, however, this scenario was overturned as electron-spin-resonance (ESR) studies unveiled a spin gap, calling for reevaluation of the magnetic ground state. Here we achieve a precise mapping of this spin-gapped phase through the Mott transition by ultrahigh-resolution strain tuning. Our transport experiments reveal a reentrance of charge localization below T⋆ = 6 K associated with a gap size of 30-50 K. The negative slope of the insulator-metal boundary, dT⋆/dp < 0, evidences the low-entropy nature of the spin-singlet ground state. By tuning the enigmatic '6K anomaly' through the phase diagram of κ-(BEDT-TTF)2Cu2(CN)3, we identify it as the transition to a valence-bond-solid phase, in agreement with previous thermal expansion and magnetic resonance studies. This spin-gapped insulating state persists at T → 0 until unconventional superconductivity and metallic transport proliferate.

2.
Phys Rev Lett ; 128(2): 027201, 2022 Jan 14.
Article in English | MEDLINE | ID: mdl-35089746

ABSTRACT

A Dirac electron system in solids mimics relativistic quantum physics that is compatible with Maxwell's equations, with which we anticipate unified electromagnetic responses. We find a large orbital diamagnetism only along the interplane direction and a nearly temperature-independent electrical conductivity of the order of e^{2}/h per plane for the new 2D Dirac organic conductor, α-(BETS)_{2}I_{3}, where BETS is bis(ethylenedithio)tetraselenafulvalene. Unlike conventional electrons in solids whose nonrelativistic effects bifurcate electric and magnetic responses, the observed orbital diamagnetism scales with the electrical conductivity in a wide temperature range. This demonstrates that an electromagnetic duality that is valid only within the relativistic framework is revived in solids.

3.
Diabet Med ; 34(7): 909-915, 2017 07.
Article in English | MEDLINE | ID: mdl-27925270

ABSTRACT

AIMS: A majority of children with Type 1 diabetes in Japan are registered with the government-subsidized Specified Pediatric Chronic Disease Treatment Research Projects (SPCDTRP). In this study, the incidence and prevalence of childhood-onset (< 15 years) Type 1 diabetes in Japan were estimated by drawing on SPCDTRP data. METHODS: Data available for 2005-2012 from the SPCDTRP and Statistics Bureau, Ministry of Internal Affairs and Communications were used to estimate the incidence of Type 1 diabetes for 2005-2010, adjusted to cover those registered within 3 years of disease onset and stratified by sex, age at onset and period of onset. RESULTS: The incidence of Type 1 diabetes for 2005-2010 was 2.25/100,000 persons [95% confidence intervals (95% CI), 2.14-2.36] (boys: 1.91, 95% CI, 1.83-1.98; girls: 2.52, 95% CI, 2.34-2.69), with that for the age brackets 0-4, 5-9 and 10-14 years being 1.48 (95% CI, 1.29-1.66), 2.27 (95% CI, 2.08-2.47) and 3.00 (95% CI, 2.74-3.25), respectively. The onset of disease was shown to peak at age 13 among boys (3.28, 95% CI, 3.02-3.55) and at age 10 among girls (3.28, 95% CI, 3.02-3.55). The peak periods of disease onset were April/May and December. The number of children aged < 15 years with Type 1 diabetes for 2005-2012 was estimated to be 2326 (95% CI, 2202-2450) with the prevalence estimated as 13.53/100,000 persons (95% CI, 12.63-14.43). CONCLUSIONS: Study findings demonstrated no increase in the incidence of Type 1 diabetes, although suggesting, in agreement with earlier reports, that the onset of disease peaks in adolescence with a female predominance. In addition, the incidence of childhood-onset diabetes exhibited an annual bimodal pattern in this study.


Subject(s)
Diabetes Mellitus, Type 1/epidemiology , Health Transition , Adolescent , Age of Onset , Child , Child, Preschool , Diabetes Mellitus, Type 1/ethnology , Female , Humans , Incidence , Japan/epidemiology , Male , Prevalence , Registries , Seasons , Sex Factors , State Medicine
4.
Phys Rev Lett ; 114(10): 106401, 2015 Mar 13.
Article in English | MEDLINE | ID: mdl-25815951

ABSTRACT

Pressure dependence of the conductivity and thermoelectric power is measured through the Mott transition in the layer organic conductor EtMe_{3}P[Pd(dmit)_{2}]_{2}. The critical behavior of the thermoelectric effect provides a clear and objective determination of the Mott-Hubbard transition during the isothermal pressure sweep. Above the critical end point, the metal-insulator crossing, determined by the thermoelectric effect minimum value, is not found to coincide with the maximum of the derivative of the conductivity as a function of pressure. We show that the critical exponents of the Mott-Hubbard transition fall within the Ising universality class regardless of the dimensionality of the system.

5.
Diabetes Obes Metab ; 12(7): 613-22, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20590736

ABSTRACT

OBJECTIVE: To compare the efficacy and safety of sitagliptin (a dipeptidyl peptidase-4 inhibitor) and voglibose (an alpha-glucosidase inhibitor) monotherapy in Japanese patients with type 2 diabetes who have inadequate glycaemic control (HbA1c > or =6.5% and <10.0%) on diet and exercise. METHODS: In a multi-center, randomized, double-blind, parallel-group study, 319 patients were randomized (1:1) to 12-week treatment with sitagliptin 50 mg once daily or voglibose 0.2 mg thrice daily before meals. The primary analysis assessed whether sitagliptin was non-inferior to voglibose in lowering HbA1c. RESULTS: After 12 weeks, sitagliptin was non-inferior to voglibose for HbA1c-lowering efficacy. Furthermore, sitagliptin was superior to voglibose, providing significantly greater reductions in HbA1c from baseline [least squares mean changes in HbA1c [95% confidence intervals (CI)] = -0.7% (-0.8 to -0.6) and -0.3% (-0.4 to -0.2), respectively; between-group difference = -0.4% (-0.5 to -0.3), p < 0.001]. Sitagliptin was also superior to voglibose on other key efficacy endpoints, including change from baseline in 2-h postmeal glucose (-2.8 mmol/l vs. -1.8 mmol/l, p < 0.001) and fasting plasma glucose (-1.1 mmol/l vs. -0.5 mmol/l, p < 0.001). After 12 weeks, the incidences of clinical adverse experiences (AEs), drug-related AEs and gastrointestinal AEs in the sitagliptin group (48.5, 10.4 and 18.4%, respectively) were significantly (p < 0.05) lower than those in the voglibose group (64.7, 26.3 and 34.6%, respectively). The incidences of hypoglycaemia, serious AEs and discontinuations due to AEs were low and similar in both groups. CONCLUSIONS: In Japanese patients with type 2 diabetes, once-daily sitagliptin monotherapy showed greater efficacy and better tolerability than thrice-daily voglibose over 12 weeks.


Subject(s)
Asian People , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/administration & dosage , Hypoglycemic Agents/administration & dosage , Inositol/analogs & derivatives , Pyrazines/administration & dosage , Triazoles/administration & dosage , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Double-Blind Method , Drug Administration Schedule , Female , Glycated Hemoglobin , Humans , Hypoglycemic Agents/pharmacology , Inositol/administration & dosage , Inositol/pharmacology , Male , Middle Aged , Pyrazines/pharmacology , Sitagliptin Phosphate , Treatment Outcome , Triazoles/pharmacology
6.
Diabetologia ; 53(4): 600-5, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20012011

ABSTRACT

This article presents the conclusions of a WHO Expert Consultation that evaluated the utility of the 'metabolic syndrome' concept in relation to four key areas: pathophysiology, epidemiology, clinical work and public health. The metabolic syndrome is a concept that focuses attention on complex multifactorial health problems. While it may be considered useful as an educational concept, it has limited practical utility as a diagnostic or management tool. Further efforts to redefine it are inappropriate in the light of current knowledge and understanding, and there is limited utility in epidemiological studies in which different definitions of the metabolic syndrome are compared. Metabolic syndrome is a pre-morbid condition rather than a clinical diagnosis, and should thus exclude individuals with established diabetes or known cardiovascular disease (CVD). Future research should focus on: (1) further elucidation of common metabolic pathways underlying the development of diabetes and CVD, including those clustering within the metabolic syndrome; (2) early-life determinants of metabolic risk; (3) developing and evaluating context-specific strategies for identifying and reducing CVD and diabetes risk, based on available resources; and (4) developing and evaluating population-based prevention strategies.


Subject(s)
Cardiovascular Diseases/epidemiology , Metabolic Syndrome/physiopathology , Diabetes Mellitus/epidemiology , Metabolic Syndrome/classification , Metabolic Syndrome/epidemiology , Metabolic Syndrome/prevention & control , Obesity/epidemiology , Patient Education as Topic , Public Health , Risk Factors , World Health Organization
7.
Br J Ophthalmol ; 93(6): 726-30, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19282301

ABSTRACT

AIM: The aim of the study was to investigate trends in the incidence of blindness and the association with laser photocoagulation in patients with type 1 diabetes in Japan. METHODS: Patients diagnosed between 1965 and 1979 aged under 18 years old were studied. The status of blindness and laser photocoagulation was identified as of 1 January 1995. To examine the time trend, we divided the cohort into two groups: 285 patients diagnosed between 1965 and 1969 (65-69 cohort) and 769 patients diagnosed between 1975 and 1979 (75-79 cohort). Survival analysis was performed using the Kaplan-Meier method. Cox proportional hazard models were used to assess the demographic characteristics. RESULTS: Blindness developed in 60 subjects in the 65-69 cohort and 15 subjects in the 75-79 cohort. The incidence of blindness in the 75-79 cohort was significantly lower than that in the 65-69 cohort (p<0.0001). In spite of no change in the use of laser photocoagulation in the 75-79 cohort compared with the 65-69 cohort, the hazard ratio for the blindness in those who received laser photocoagulation in the 75-79 cohort decreased significantly to 0.55 (p<0.01) compared with those in the 65-69 cohort when adjusted for the age of onset, sex, and time of diagnosis. CONCLUSION: The incidence of blindness decreased significantly for the subjects diagnosed more recently. The change in quality and the earlier introduction of laser photocoagulation might have contributed to the decreased incidence of blindness observed over time.


Subject(s)
Blindness/etiology , Diabetes Mellitus, Type 1/complications , Diabetic Retinopathy/surgery , Laser Coagulation/statistics & numerical data , Adolescent , Age of Onset , Blindness/epidemiology , Blindness/prevention & control , Child , Child, Preschool , Diabetes Mellitus, Type 1/epidemiology , Diabetic Retinopathy/complications , Diabetic Retinopathy/epidemiology , Epidemiologic Methods , Female , Humans , Japan/epidemiology , Male
8.
Endocrine ; 29(2): 309-15, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16785606

ABSTRACT

OBJECTIVE: The effect of single-dose mitiglinide on glucose and lipid metabolism was examined in OLETF rats with spontaneous type 2 diabetes in which the early insulin response following glucose challenge is known to diminish over time and become lost with aging. METHODS: (1) With catheters inserted into the portal veins, 12-wk-old prediabetic OLETF rats were given an OGTT of 1 g/kg after 17 h of fasting. Eight rats each were orally given mitiglinide 1 mg/kg, nateglinide 50 mg/kg, or glibenclamide 1 mg/kg, vs 0.5% carboxymethylcellulose (CMC) as control, and were given an OGTT immediately afterward. Following oral administration of mitiglinide, nateglinide, glibenclamide, or 0.5% CMC, the 24-wk-old overt-diabetic OLETF rats were immediately given an OGTT of 1g/kg. (2) After 17 h of fasting, 24-wk-old OLETF rats were subjected to a fat-loading test. Eight rats each were given mitiglinide 3 mg/kg, glibenclamide 1 mg/kg, or glimepiride 1 mg/kg, vs 0.5% CMC, and were given soy oil 2 g/kg immediately afterward. They were also given mitiglinide orally and examined for LPL mRNA expression in their adipose tissue. RESULTS: (1) After OGTT, mitiglinide produced a significant increase in portal insulin levels 15 min after its administration, as well as a significant decrease in peripheral glucose levels 15-120 min after its administration in the OLETF rats. Likewise, nateglinide produced an increase in portal insulin levels and a decrease in peripheral glucose levels shortly after its administration in these rats. Glibenclamide increased portal insulin levels for an extended time after its administration, and significantly decreased peripheral glucose levels in the rats 120-300 min after its administration in the rats. In contrast, as in the 12-wk-old rats, a precipitous rise in insulin secretion was seen in the portal vein of 24-wk-old rats given mitiglinide, which peaked 15 min after mitiglinide administration, but the insulin levels continued to increase for 120 min or longer in the 24-wk-old rats given glibenclamide. In addition, as in the 12-wk-old rats, a significant decrease in glucose levels in peripheral blood was noted 30 and 60 min after mitiglinide administration and 300 min after glibenclamide administration in the 24-wk-old rats. (2) Mitiglinide increased LPL mRNA expression 120 min after its administration, and significantly decreased peripheral TG and chylomicron- TG levels after fat challenge in the 24-wk-old OLETF rats. CONCLUSION: Mitiglinide exhibited fast-onset and short-acting insulin-secretagogic effects, inhibiting post-glucose challenge increases in glucose levels and post-fat challenge increases in TG levels.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Indoles/pharmacology , Insulin/blood , Prediabetic State/drug therapy , Triglycerides/blood , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Animals , Blood Glucose/metabolism , Cyclohexanes/pharmacology , Glucose Tolerance Test , Glyburide/pharmacology , Insulin/metabolism , Insulin Secretion , Isoindoles , Lipoprotein Lipase/metabolism , Male , Nateglinide , Phenylalanine/analogs & derivatives , Phenylalanine/pharmacology , Portal Vein , Postprandial Period , RNA, Messenger/metabolism , Rats , Rats, Inbred OLETF , Sulfonylurea Compounds/pharmacology
9.
Diabetologia ; 49(6): 1264-73, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16570155

ABSTRACT

AIMS/HYPOTHESIS: Ghrelin, a stomach-derived hormone, functions in multiple biological processes, including glucose metabolism and cellular differentiation and proliferation. In this study, we examined whether early treatment with ghrelin can regenerate beta cells of the pancreas in an animal model of diabetes mellitus, the n0-STZ model, in which neonatal rats are injected with streptozotocin (STZ) at birth. METHODS: Following administration of ghrelin to n0-STZ rats from postnatal days 2 to 8, we examined beta cell mass, mRNA expression levels of insulin and of pancreatic and duodenal homeobox 1 (Pdx1) gene, and pancreatic morphology on days 21 and 70. In addition, we investigated the effects of ghrelin on beta cell replication. RESULTS: By day 21, ghrelin treatment increased pancreatic expression of insulin and Pdx1 mRNA in n0-STZ rats. The number of replicating cells was also significantly increased in the ghrelin-treated n0-STZ model. At day 70, n0-STZ rats exhibited hyperglycaemia, despite slight increases in plasma insulin levels. Ghrelin treatment resulted in the improvement of plasma glucose levels, which were associated with normal plasma insulin levels. Pancreatic insulin mRNA and protein levels were significantly increased in ghrelin-treated n0-STZ model animals. CONCLUSIONS/INTERPRETATION: These findings suggest that ghrelin promotes regeneration of beta cells in STZ-treated newborn rats. Thus, early administration of ghrelin may help prevent the development of diabetes in disease-prone subjects after beta cell destruction.


Subject(s)
Diabetes Mellitus, Experimental/prevention & control , Peptide Hormones/therapeutic use , Aging , Animals , Animals, Newborn , Blood Glucose/drug effects , Blood Glucose/metabolism , Cell Division , Female , Ghrelin , Insulin/blood , Insulin/genetics , Insulin/metabolism , Insulin Secretion , Insulin-Secreting Cells/cytology , Male , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Streptozocin/pharmacology
10.
Phys Rev Lett ; 95(22): 227801, 2005 Nov 25.
Article in English | MEDLINE | ID: mdl-16384266

ABSTRACT

Optical conductivity measurements on the organic metal theta-(BEDT-TTF)2I3 revealed that the system crosses over rapidly from a coherent quasiparticle state to an incoherent state with temperature. Despite the metallic temperature dependence of resistivity, a well-defined Drude peak at low temperatures turns into a far-infrared peak with temperature. The peak energy shifts to higher frequencies and, simultaneously, the spectral weight is transferred to high frequencies beyond the electron band width. These characteristics imply that theta-(BEDT-TTF)2I3, so far believed to be a typical metal, is in fact a strongly correlated electron system with "bad-metal" character.


Subject(s)
Organometallic Compounds/chemistry , Spectrum Analysis/methods , Sulfhydryl Compounds/chemistry , Electric Conductivity , Optics and Photonics , Protons , Thermodynamics
11.
Exp Clin Endocrinol Diabetes ; 113(6): 334-9, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15977101

ABSTRACT

BACKGROUND: Impaired glucose tolerance (IGT) represents a stage of pre-diabetes and is a risk factor for future cardiovascular disease (CVD) which is a major cause of death in type 2 diabetes. The metabolic risk factors such as elevated blood pressure (elevated BP), abdominal obesity, dyslipidemia (elevated levels of total triglycerides [TG] and low levels of HDL cholesterol), and hyperglycemia precede the onset of the metabolic syndrome that increases the risk for CVD. This clustering is commonly associated with pre-diabetic hyperinsulinemia and it reflects peripheral insulin resistance. The present study documented that a visceral fat area (VFA) >/= 100 cm (2) can replace waist-to-hip ratios (WHR) associated with IGT or IFG/IGT as a critical risk for the development of the metabolic syndrome in Japanese middle-aged men. MATERIALS AND METHODS: A total of 575 middle-aged Japanese men with fasting plasma glucose levels of 6.1 - 6.9 mmol/l (impaired fasting glucose; IFG) were enrolled in the study. After a 75-g oral glucose tolerance test (OGTT), blood samples were collected 0 - 2 h later for determination of plasma glucose, insulin concentrations and other variables. Based on the results of an OGTT, the subjects were subgrouped into categories of glucose tolerance for further study. RESULTS: Subjects with IGT or IFG/IGT had significantly higher levels of metabolic abnormalities such as high BMI, increased AUC glucose, elevated HbA1c, high VFA, elevated BP, and increased TG levels when compared to NGT (normal glucose tolerance) (p < 0.001). Compensatory hyper-secretion of insulin was seen in all pre-diabetic subjects, and was higher in IFG/IGT subjects (681 +/- 33 pmol . h/l) than NGT (480 +/- 22 pmol . h/l) (p < 0.01). The metabolic clustering including abnormal VFA, TG, HDL-C, and BP was strongly associated with the development of metabolic syndrome. Interestingly, VFA >/= 100 cm (2) adjusted for the Japanese correlates strongly with the development of the metabolic syndrome in preclinical IGT or IFG/IGT subjects, with odds ratios of 2.7 and higher. CONCLUSION: VFA >/= 100 cm (2) strongly correlates with prediabetic IGT or IFG/IGT which is possibly associated with underlying insulin resistance, and is a critical risk factor linked to the development of metabolic syndrome in Japanese middle-aged subjects with IGT or IFG/IGT.


Subject(s)
Adipose Tissue/metabolism , Blood Glucose/metabolism , Metabolic Syndrome/metabolism , Blood Pressure/physiology , Body Mass Index , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Cholesterol/blood , Glucose Tolerance Test , Glycated Hemoglobin/metabolism , Humans , Insulin Resistance/physiology , Japan , Logistic Models , Male , Metabolic Syndrome/blood , Middle Aged , Predictive Value of Tests , Risk Factors
13.
Diabetes Obes Metab ; 7(2): 182-8, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15715891

ABSTRACT

AIM: The aim of this study was to investigate the influence of changes in insulin resistance and early insulin secretion on the insulin secretagogic effects of nateglinide. METHODS: Oral glucose tolerance testing (OGTT, 75 g) was performed in obese patients before and after weight loss on 2 consecutive days (first day OGTT without nateglinide, second day OGTT with nateglinide), to compare any weight loss associated changes in the nateglinide-induced insulin response to glucose loading. RESULTS: Reductions in visceral fat, liver fat, skeletal muscle fat and homeostasis model assessment (HOMA)-R due to weight loss were associated with increased Delta insulin 30 min/Delta glucose 30 min (DeltaI30/DeltaG30), and reduced area under the curve (AUC) for plasma glucose as seen in OGTT results. Results from OGTT showed that nateglinide administration was associated with reductions in plasma glucose AUC, both before and after weight loss. Before weight loss, although there was a significant elevation of DeltaI30/DeltaG30 associated with nateglinide treatment, no major change in the insulin-secreting dynamics after glucose loading was observed. After weight loss, nateglinide administration produced a significant increase in DeltaI30/DeltaG30, with insulin secretion peaking more quickly. CONCLUSION: Insulin response to nateglinide after glucose loading varied greatly in conjunction with weight loss. This may be accounted for not only by the enhancement of early insulin response to nateglinide associated with the improvement of early insulin response with weight loss but also by the reduced visceral fat, which in turn led to reduced levels of free fatty acids in portal blood and hepatic triglycerides, as well as increased hepatic insulin clearance.


Subject(s)
Cyclohexanes/administration & dosage , Hypoglycemic Agents/administration & dosage , Insulin/metabolism , Obesity/drug therapy , Phenylalanine/analogs & derivatives , Phenylalanine/administration & dosage , Weight Loss/physiology , Adipose Tissue/drug effects , Administration, Oral , Blood Glucose/analysis , C-Peptide/blood , Fatty Acids, Nonesterified/blood , Female , Glucose Tolerance Test , Homeostasis/drug effects , Humans , Insulin/analysis , Insulin Resistance/physiology , Insulin Secretion , Liver/drug effects , Male , Middle Aged , Muscle, Skeletal/drug effects , Nateglinide , Obesity/physiopathology
14.
Diabet Med ; 22(12): 1636-41, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16401305

ABSTRACT

AIMS: Excess mortality in Type 1 diabetes has previously been found among Black individuals. The aim of the present study was therefore to determine underlying causes. METHODS: A longitudinal study of 1261 [1184 White (93.9%) and 76 Black (6.0%)] individuals diagnosed with Type 1 diabetes between 1965 and 1979, at age<17 years from the Allegheny County, Pennsylvania and Children's Hospital of Pittsburgh registries. Subjects were contacted in 1999 to determine living status and, where appropriate, cause of death. Living status was determined in 1183 participants (93.8%). RESULTS: Of the 200 deaths overall, cause of death was determined in 157 subjects (79%); 31 dying from acute and 101 from chronic complications, and 25 from non-diabetes related causes. Seven deaths were investigated but no cause determined. Black participants had a significantly higher mortality rate compared with White participants for acute complications (hazard ratio=4.9, 95% confidence interval: 2.0, 11.6), but not for any other cause. There was a temporal decline in the 20-year mortality rates in both racial groups across the three cohorts diagnosed in 1965-69, 1970-74 and 1975-79. CONCLUSIONS: These results show that the excess mortality in Black people was attributed to acute complications which therefore should be a focus for prevention.


Subject(s)
Black or African American/ethnology , Diabetes Mellitus, Type 1/mortality , White People/ethnology , Adolescent , Cause of Death , Child , Child, Preschool , Cohort Studies , Diabetes Mellitus, Type 1/ethnology , Female , Humans , Longitudinal Studies , Male , Pennsylvania/epidemiology
15.
Diabetes Obes Metab ; 6(6): 422-31, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15479218

ABSTRACT

AIM: The aim of this study was to clarify the role of an early insulin secretion in postprandial hyperglycaemia and hyperlipidaemia; a study using spontaneously type 2 diabetic Otsuka Long-Evans Tokushima Fatty rats with visceral obesity was performed to investigate the acute effect of nateglinide (NAT) vs. glibenclamide (GB) on increases in glucose after glucose loading and on increases in triglyceride (TG) after fat loading. METHODS: Fasting rats were given 50 mg/kg of NAT, 1 mg/kg of GB or 5% methyl cellulose (vehicle) as control and then immediately given oral glucose 1 g/kg. RESULTS: An acute increase in insulin levels in portal blood peaked at 15 min in the NAT group, while insulin levels in the GB group continued to increase significantly after 60 min. Glucose levels in peripheral blood were significantly lower in the NAT group at 30 and 60 min and in the GB group at 120, 180 and 270 min after glucose loading, compared with those in the vehicle group. Subsequently, fasting rats were given NAT, GB or vehicle and then immediately given oral fat emulsion (soy oil 2 g/kg). An acute increase in insulin secretion was seen with NAT, peaking at 30 min, while TG, chylomicron and very low-density lipoprotein levels after fat loading were shown to be significantly lower with NAT than with vehicle. However, the continued insulin secretion observed with GB led to no significant decrease in TG levels after fat loading. In addition, lipoprotein lipase mRNA expression in adipose tissue increased significantly 120 min after NAT administration in comparison with baseline. This increase was not noted with GB administration. CONCLUSION: Abnormalities in early insulin secretion are closely associated with the pathogenesis of various disease conditions that combine to characterize type 2 diabetes, suggesting that normalizing early insulin response in portal blood represents an important treatment not only for postprandial hyperglycaemia but also for postprandial hyperlipidaemia.


Subject(s)
Diabetes Mellitus, Type 2/blood , Hyperglycemia/blood , Hyperlipidemias/blood , Hypoglycemic Agents/pharmacology , Insulin/metabolism , Phenylalanine/analogs & derivatives , Adipose Tissue/metabolism , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , Cyclohexanes/pharmacology , Dietary Fats/pharmacology , Gene Expression Regulation/drug effects , Glyburide/pharmacology , Insulin/blood , Insulin Secretion , Lipoprotein Lipase/biosynthesis , Lipoprotein Lipase/genetics , Male , Nateglinide , Phenylalanine/pharmacology , Postprandial Period , RNA, Messenger/genetics , Rats , Rats, Inbred OLETF , Rats, Long-Evans , Triglycerides/blood
17.
Diabetes Obes Metab ; 6(1): 28-34, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14686960

ABSTRACT

AIM: The aim of this study was to compare the effects of glimepiride and glibenclamide on tumour necrosis factor (TNF)-alpha expression and adipocyte cellularity in spontaneously diabetic, obese rats. METHODS: Eight-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were randomized to receive glimepiride, glibenclamide or control treatment for 12 weeks, after which TNF-alpha mRNA levels, adipose tissue cellularity and physiological parameters were measured. RESULTS: TNF-alpha mRNA expression in retroperitoneal fat tissue was significantly greater in the glibenclamide group (2.2 +/- 1.1), compared with the control group (0.9 +/- 0.4; p<0.05) or the glimepiride group (0.9 +/- 0.2; p<0.01). The mean fat-cell area in retroperitoneal fat tissue was increased at study endpoint in the glibenclamide group (13,764 +/- 7036 microm2), compared with both the control and glimepiride groups (10,755 +/- 6193 microm2 and 11,317 +/- 5646 microm2 respectively; p<0.05). Investigation of cellularity revealed a decrease in the frequency of small fat cells and an increase in the frequency of large fat cells in both the glibenclamide and glimepiride groups compared with the control group, with a greater increase in large fat cells in the glibenclamide group. At study endpoint, insulin and triglyceride values were significantly higher in the active treatment groups compared with the control group; however, insulin levels were significantly greater in glibenclamide-treated animals compared with glimepiride-treated animals. An oral glucose tolerance test performed at the end of the study showed that there were no significant differences among the three groups in terms of plasma glucose and insulin concentrations. CONCLUSIONS: This study suggests that although both glibenclamide and glimepiride may have a hypertrophisizing effect on fat cells in adipose tissues, this effect is greater with glibenclamide, leading to augmentation of TNF-alpha mRNA expression and possible exacerbation of insulin resistance.


Subject(s)
Adipose Tissue/drug effects , Diabetes Mellitus/metabolism , Glyburide/pharmacology , Hypoglycemic Agents/pharmacology , Obesity , Sulfonylurea Compounds/pharmacology , Adipose Tissue/metabolism , Adipose Tissue/pathology , Animals , Diabetes Mellitus/pathology , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Gene Expression Regulation/drug effects , Male , RNA, Messenger/genetics , Rats , Rats, Inbred OLETF , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/genetics
18.
Peptides ; 23(12): 2163-8, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12535694

ABSTRACT

Adrenomedullin (AM) is a 52 amino acid peptide that is synthesized in a variety of tissues, including the vessels and bones. This study showed that normal human osteoblast (NHOst) secreted immunoreactive AM and that AM stimulated intracellular cAMP production in these cells. An anti-AM monoclonal antibody, which inhibited endogenous AM, caused the number of NHOst to decrease. The effect of a low concentration AM was inhibited by addition of a cAMP-dependent protein kinase A inhibitor (H89). These data suggest that AM is an autocrine or paracrine regulator that promotes the proliferation of NHOst via the cAMP pathway.


Subject(s)
Autocrine Communication/physiology , Osteoblasts/metabolism , Paracrine Communication/physiology , Peptides/metabolism , Adrenomedullin , Antibodies, Monoclonal/immunology , Cell Division/physiology , Cyclic AMP/metabolism , Dose-Response Relationship, Drug , Humans , Peptides/immunology , Radioimmunoassay , Time Factors
19.
J Atheroscler Thromb ; 8(1): 7-13, 2001.
Article in English | MEDLINE | ID: mdl-11686314

ABSTRACT

We established a strategy to directly measure cholesterol and triglyceride levels of each lipoprotein fraction using a combination of agarose gel electrophoresis and differential staining. The cholesterol and triglyceride levels determined by electrophoresis correlated significantly with those of ultracentrifugation. The correlation coefficients between these methods were, for cholesterol levels 0.975(very low density lipoproteins, VLDL), 0.986(low density lipoproteins, LDL) and 0.965(high density lipoproteins, HDL) and for triglyceride levels 0.994(VLDL), 0.963(LDL) and 0.959(HDL) respectively. Both intra-and inter-assays showed low values of coefficients of variation (CV) (less than 3.57%). We observed a strong linearity between staining and triglyceride concentration. An increased VLDL-cholesterol was observed in type III subjects, a result which enabled distinction between type III and type IIb or type V lipoproteinemia. The method revealed lipoprotein patterns in some samples otherwise unexpected from their corresponding serum lipid parameters. Analyses of these electrophoretic patterns thus provide an effective technique to classify types of hyperlipidemia defined by the WHO. Furthermore, quantitative measurement of chylomicrons, usually difficult, proved to be achievable, providing an additional analysis of postprandial hyperlipidemia and the exact measurement of LDL-cholesterol after diet. Consequently, we recommend this simple and easy method for clinical evaluation of abnormalities in lipoprotein profiles.


Subject(s)
Electrophoresis, Agar Gel/methods , Hyperlipidemias/diagnosis , Lipoproteins/blood , Chylomicrons/blood , Humans , Hyperlipidemias/classification , Image Processing, Computer-Assisted , Linear Models , Lipids/analysis , Lipoproteins/analysis , Software , Staining and Labeling/methods , Ultracentrifugation/methods
20.
Okajimas Folia Anat Jpn ; 78(1): 1-5, 2001 May.
Article in English | MEDLINE | ID: mdl-11552285

ABSTRACT

Myelinated axons of the human vagus nerve were analyzed morphometrically on 30 cadavers (16 males and 14 females). The result showed that the transverse area and perimeter of myelinated axons decreased with age, although the total number of their axons did not change.


Subject(s)
Nerve Fibers, Myelinated , Vagus Nerve/cytology , Adult , Aged , Aged, 80 and over , Cell Count , Female , Humans , Male , Middle Aged
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