Hiroko Yasuda

Stimulation of guanosine 3′,5′-cyclic monophosphate accumulation in rat anterior pituitary gland in vitro by synthetic somatostatin

Abstract Synthetic somatostatin stimulated cyclic GMP accumulation with dose dependency (10 ng/ml – 10 μg/ml in a dose examined) in rat anterior pituitary gland in vitro. The stimulation of cyclic GMP levels in the gland was observed after 2 min incubation with somatostatin. Cyclic AMP production induced by TRH or PGE 1 was supressed by this GH release inhibiting factor, while cyclic GMP concentration in the gland was elevated. The present results seem to suggest that inhibitory effect on GH release by somatostatin in anterior pituitary gland is mediated through change in concentration of cyclic AMP and cyclic GMP in the target cells.

Effect of glucose on protein phosphorylation in rat pancreatic islets

Isolated rat pancreatic islets, incubated in the presence of extracellular 32Pi to steady state 32P incorporation into cellular phosphopeptides, were exposed to glucose for 10 min. Glucose (16.7 mM) significantly stimulated the phosphorylation of six phosphoproteins with molecular weights of 15,000, 35,000, 49,000, 64,000, 93,000 and 138,000. Mannoheptulose (16.7 mM) markedly inhibited glucose-stimulated phosphorylation of these six phosphoproteins. This protein phosphorylation might be important in mediating glucose-stimulated insulin release.

A Decreased Response of Cyclic Adenosine Monophosphate Concentrations to Glucagon in Liver Slices from Streptozotocin-induced Diabetic Rats

Responses to glucagon from the adenylate cyclasecyclic adenosine monophosphate (cAMP) system in liver slices from control and streptozotocin-induced diabetic rats were compared. Tissue cAMP levels were similar in the basal state but responded poorly to glucagon (20 pg/ml-2 μg/ml) in diabetic rats. Insulin treatment of diabetic rats in vivo led to a reversal of the glucagon stimulation towards the values in the control rats. The basal and glucagon-stimulated activities of adenylate cyclase in crude membrane fractions were similar in both groups. Plasma immunoreactive glucagon levels in diabetic rats were approximately three times higher than those in normal rats. Liver slices obtained from normal rats, which were injected with glucagon (0.2 mg, i.m.) 45 min previously, also showed an impaired responsiveness to glucagon of tissue cAMP levels, while no significant difference in adenylate cyclase activity was observed between the normal and glucagon-treated rats. These results suggest that the responsiveness of liver slices from the streptozotocin-induced diabetic rat has been modified by the preceding hyperglucagonemia. The reason for the observed differences between slices and crude membranes is not known.

Vital Capacity and Selected Metabolic Diseases in Middle-Aged Japanese Men

OBJECTIVE To elucidate the association between vital capacity and the presence of selected metabolic diseases in middle-aged Japanese men. METHODS A cross-sectional analysis of the associations among forced vital capacity (FVC), static vital capacity as a percentage of that predicted (%VC) and the presence of metabolic diseases was performed. RESULTS In a univariate linear regression analysis, FVC and %VC were inversely associated with poor vegetable intake, cigarette smoking and body mass index, but not with physical activity or ethanol consumption. In a logistic regression analysis adjusted for lifestyle factors, body mass index and age, the odds ratios for the presence of metabolic disease per 0.54 L (1 SD) decrease in FVC were 1.24 (95% CI 1.03 to 1.50) for type II diabetes, 1.21 (95% CI 1.02 to 1.42) for hypertension, 1.34 (95% CI 1.11 to 1.63) for hypertriglyceridemia, 1.23 (95% CI 1.03 to 1.46) for high gamma-glutamyl transferase levels and 1.63 (95% CI 1.10 to 2.41) for an episode of cardiovascular disease. FVC did not correlate with hyperhomocysteinemia, hypercholesterolemia or high white blood cell count. Similar results were also obtained for the association between %VC and metabolic diseases. CONCLUSIONS A decrease in FVC or %VC was associated with the presence of some metabolic diseases. The association may partly explain the reported association between low FVC and cardiovascular disease.

Beverage-specific effects of ethanol consumption on its biological markers

Abstract Background: Serum γ-glutamyltransferase (GGT) and erythrocyte mean corpuscular volume (MCV) are well-known biological markers of excessive ethanol consumption. Methods: The beverage-specific effects of ethanol consumption on GGT level and MCV value were analyzed cross-sectionally and retrospectively among middle-aged Japanese men who underwent a retirement health checkup (n=974). Results: Both the consumption of distilled alcohol and that of fermented alcohol positively correlated with the logarithm of GGT [standard regression coefficient (β) 0.261 and 0.174, respectively]. The prevalence rate of elevated GGT levels (≥70 IU/L) was higher among heavy drinkers of distilled alcohol than among heavy drinkers of fermented alcohol (38.8% vs. 27.6%, p=0.013). The MCV value correlated with distilled alcohol consumption (β: 0.212, p<0.0001) but not with fermented alcohol consumption (β: 0.043, not significant). The prevalence rate of an elevated MCV (≥97 fL) was higher among heavy drinkers of distilled alcohol than among heavy drinkers of fermented alcohol (35.3% vs. 16.8%, p<0.001). Conclusions: These results suggest that MCV is less sensitive for detecting heavy consumption of fermented alcohol than for detecting that of distilled alcohol in apparently healthy middle-aged men. Clin Chem Lab Med 2008;46:699–702.

Relationship Between Alcohol Consumption, Body Weight, Family History of Hypertension and Blood Pressure in Young Adults

It is not clear why blood pressure rises with age in civilized countries. We examined the relationship between alcohol consumption, obesity, family history of hypertension and blood pressures at medical checkups in 534 male office workers, aged 20 to 40. The results in two age groups, 20-30 and 31-40, are as follows. Those who drank heavily (greater than 60 ml of ethanol) the previous night and/or habitual heavy drinkers (greater than 60 ml/day) had the highest blood pressure. Obese workers had higher blood pressure. Subjects with a family history of hypertension had higher blood pressure. The frequencies of heavy drinkers and obesity were higher in the group aged 31 to 40 than in the other group. These factors might contribute to the blood pressure elevation with age. 5) A histogram of the first readings of systolic blood pressure showed a bimodal distribution only in persons with a family history of hypertension.

Involvement of Ca2+-calmodulin in platelet-derived growth factor-, fibroblast growth factor-, and insulin-induced ornithine decarboxylase in NIH-3T3 cells

Ornithine decarboxylase (ODC) was induced by platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and insulin at doses ranging from 0.125 to 0.5 U/mL, 25 to 500 ng/mL, and 10(-8) to 10(-7) mol/L, respectively, in NIH-3T3 cells. The induction of ODC reached a plateau approximately 4 to 6 hours after addition of each mitogen. PDGF exerted a synergistic action with 10(-7) mol/L insulin until the concentration of PDGF reached 0.5 U/mL and exerted an additive action at concentrations greater than 0.5 U/mL. FGF also accelerated ODC induction by insulin (10(-7) mol/L) synergistically when it was added at doses up to 500 ng/mL. PDGF added to the intact monolayer cells caused a spike-and-plateau increase in cytosolic Ca2+ concentration ([Ca2+]i); the spike was independent of extracellular Ca2+, whereas the plateau formation was dependent on extracellular Ca2+. On the other hand, FGF caused a plateau-like increase in [Ca2+]i, exclusively dependent on extracellular Ca2+. Insulin did not affect [Ca2+]i in NIH-3T3 cells. Trifluoperazine (15 to 30 mumol/L) inhibited the induction of ODC by PDGF and FGF, but did not inhibit the effect of insulin to induce ODC. N-(6-aminohexyl)-5-chloro-1-Naphthalenesulfonamide ([W-7] 30 to 40 mumol/L) showed a more profound suppressive effect on ODC induced by PDGF and FGF than N-(6-aminohexyl)-naphthalenesulfonamide (W-5) did. There was no difference between the effects of W-7 and W-5 on ODC induction by insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma folate levels in men with type 2 diabetes

Limited data suggest that folate levels are higher in patients with type 2 diabetes than in subjects with normal glucose tolerance (NGT). We compared the fasting plasma folate, glucose (FPG), body mass index (BMI), and supplementary vitamin use among male subjects with NGT, those with impaired glucose tolerance (IGT), those with newly diagnosed type 2 diabetes, and those with previously diagnosed type 2 diabetes. Plasma folate of patients with newly diagnosed diabetes and that of patients with previously diagnosed diabetes was significantly higher than that of NGT subjects (p < 0.001). Prevalence of vitamin use was lower in newly diagnosed or previously diagnosed diabetic patients compared with non-diabetic subjects. Self-rated vegetable intake was similar among the four groups. FPG, BMI, triglycerides, and systolic blood pressure correlated with plasma folate levels independently of lifestyle factors studied. These results suggest that plasma folate levels are elevated in male diabetic patients independently of health-conscious behavior that is recommended for diabetic people.

Stimulative effects of TMB-8 and trifluoperazine on pancreatic hormone release

The effects of 8-N-N-diethylamino octyl 3,4,5-trimethoxybenzoate (TMB-8) and trifluoperazine (TFP) on the early phase (10 min) of the release of pancreatic hormones from isolated rat islets were investigated. TMB-8 and TFP stimulated insulin, glucagon, and somatostatin release in a dose-dependent manner at a low glucose concentration (2.5 mM). The levels of glucagon and somatostatin release were also stimulated by these two agents at a high glucose concentration (10 mM). Their effects were independent of external calcium ion level. These two agents did not modify insulin release at the high glucose concentration. The stimulative effects of the two agents on the release of these hormones were partially suppressed when the islets were pretreated with 6-hydroxydopamine (6-OHDA), a chemical adrenergic denervator that acts at nerve endings. In this situation, the norepinephrine (NE) released from pancreatic islets decreased to 44% of that of non-treated islets (P less than 0.01). The addition of NE (10(-9) M) to the incubation medium increased insulin, glucagon, and somatostatin secretion by 20-30% over control levels (P less than 0.05). In conclusion, the early phase of pancreatic hormone release was stimulated by TMB-8 and TFP. Our results strongly suggest that these two drugs could be mediated by the NE released from nerve endings in the islets.

Usefulness of urinary glucose excretion after oral glucose tolerance testing to detect insulin secretion failure before the onset of diabetes mellitus

Sodium-glucose cotransporter 2 inhibitors are commonly used to promote urinary glucose excretion (UGE). However, it remains unclear how UGE reflects glucose metabolism in the natural history of diabetes. Thus, we retrospectively reviewed the prediabetes medical records of 64 patients who had undergone 75-g oral glucose tolerance testing (OGTT) with measurements of UGE at 0 min, 60 min, and 120 min. The mean age and glycated hemoglobin levels were 46 ± 10 years and 5.6 ± 0.3%, respectively. The median UGE (60 min + 120 min) value was 16.8 mg ([interquartile range]: [10.5-150.0 mg]). Thus, we categorized 16 patients as having high UGE (≥150.0 mg) and 48 patients as having low UGE (<150.0 mg). As compared with the low UGE group, the high UGE group exhibited a significantly lower median insulinogenic index (0.23 [0.12-0.35] vs. 0.56 [0.31-1.06], p = 0.001) and homeostasis model assessment of β-cell function value (46 [26-67] vs. 66 [41-85], p = 0.028). The log-transformed insulinogenic index exhibited a significant inverse association with log-transformed UGE (60 min + 120 min) (r = -0.50, p < 0.001). The association between higher UGE and lower insulinogenic index was also observed in a subgroup analysis of patients with plasma glucose levels of ≥160 mg/dL during the OGTT. Therefore, UGE measurements after OGTT may provide a useful clinical marker for detecting insulin secretion failure and advancing preventive and therapeutic interventions among populations with a high risk of developing diabetes.