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Biomedical subjects

M Shichiri

Publications and source records attributed to M Shichiri.

298 records · Page 17Linked to original sources

Increased intestinal absorption of insulin in a micellar solution: water-in-oil-in-water insulin micelles.

Water-in-oil-in-water (W/O/W) insulin micelles were prepared, and the possibility of insulin absorption in a micellar form was examined. In this preparation, insulin was trapped in oil droplets of oleic acid in glyceryl-alpha-monooleate. (1) W/O/W insulin micelles were absorbed from the ligated jejunal loop of rabbits to the order of 12.3 to 58.5% of the dose given (10 mU/kg body weight) during the 3-h experimental period. (2) Alloxan diabetic rats were treated with intrajejunal administration of W/O/W insulin micelles at a dosage of either 25 or 50 mU/100 g body weight, three times daily for as long as 14 days. During treatment, a significant reduction in the daily excretion of urinary glucose was observed, concomitant with a decrease in fasting blood glucose. Quantitative estimates suggested that the effectiveness of 25 mU/100 g of intrajejunal W/O/W insulin micelles was comparable to that of regular insulin at a dosage of 1 mU/100 g i.m. These results would indicate that W/O/W insulin micelles, when given enterally, are more effective in lowering blood and urinary glucose levels than W/O/W insulin emulsions in which insulin was trapped in oil droplets of triglyceride.

Animals↗

Validation of I.V. small-dose insulin infusion therapy in diabetic ketoacidosis of depancreatized dogs.

A validation of small-dose insulin infusion therapy was studied by the constant i.v. infusion of various doses of insulin into ketoacidotic depancreatized dogs. Constant insulin infusion of 5 x B, 10 X B, 30 X B and 50 X B (B = 225 microunit/kg/min) was performed for 3 h by mechanical pump. The following results were obtained: (1) plasma concentrations of immunoreactive insulin (IRI) increased proportionally to the dose of infused insulin, but the higher IRI did not result in a greater fall in plasma glucose concentration, correspondingly; the mean rate of fall in plasma glucose concentration of 5 x B was not significantly lower than that of 50 x B; beta-hydroxybutyrate and arterial pH improvements were observed in each group during the 3-h insulin infusion. These data suggested that for the improvement of diabetic ketoacidosis, the insulin infusion rate of more than 30 x B, which raised the plasma IRI levels above the physiological range, was not essential; (2) the necessity of potassium supplementation during the small-dose insulin infusion was suggested if the pre-treatment level of serum potassium was low. These results confirmed that in the absence of infection or severe acidosis small-dose insulin infusion therapy is as effective as the conventional large-dose insulin therapy.

Animals↗

Adrenomedullin receptor antagonism by calcitonin gene-related peptide(8-37) inhibits carotid artery neointimal hyperplasia after balloon injury.

Intimal injury by angioplasty results in a series of changes, including smooth muscle cell hyperplasia, that lead to vascular restenosis. Adrenomedullin, a potent vasodilator peptide, has natriuretic effects, and its plasma concentration is elevated in cardiovascular diseases. Adrenomedullin is secreted by endothelial and vascular smooth muscle cells, but its role in neointimal hyperplasia after balloon injury has not been previously described. We investigated the role of endogenous adrenomedullin in neointimal hyperplasia using an in vivo rat model of postinjury vascular restenosis. In the injured rats, bromodeoxyuridine-labeled nuclei in the media of untreated common carotid arteries were increased 2 days after injury, which were suppressed by in vivo treatment with the adrenomedullin receptor antagonist calcitonin gene-related peptide (CGRP)(8-37). Inhibition of neointimal hyperplasia by CGRP(8-37) was distinct at 7 and 14 days, whereas CGRP(1-37) had no effect. The expression of adrenomedullin in the media of both untreated and treated common carotid arteries was elevated at 2 days and further enhanced in hyperplastic intima of untreated common carotid arteries at 7 days. Our findings suggest a novel role for endogenous adrenomedullin in balloon injury-induced restenosis and indicate that CGRP(8-37) may be useful for the prevention of vascular restenosis.

Animals↗

Secondary polycythemia associated with multiple myeloma.

A 58-year-old man with polycythemia of more than 8 years duration developed multiple myeloma. Extensive examination indicated his polycythemia to be of a secondary type, but failed to reveal an underlying disorder. To the best of our knowledge, this is the first reported association of multiple myeloma in a patient with definitely-diagnosed secondary polycythemia.

Humans↗

A specific binding site for lipoproteins containing apolipoprotein A-I on human hepatoma cell line HepG2.

Interactions of lipoproteins containing apolipoprotein (apo) A-I with or without apoA-II with human hepatoma cell line HepG2 were studied to investigate the ligand specificity for high density lipoprotein receptor on human hepatic cells and their metabolism. The two types of lipoproteins were isolated by immunoaffinity chromatography, in which apoE-containing lipoproteins were removed. Specific binding kinetics at 0 degrees C were observed for the apoA-I-containing lipoproteins with or without apoA-II (Kd = 18 or 20 micrograms protein/ml, Bmax = 110 or 120 ng/mg cell protein, respectively). The binding of these lipoproteins to HepG2 cells was competitively inhibited by excess unlabeled apoA-I-containing lipoproteins or apoA-I-phospholipid complexes, but not by apoA-II.phospholipid complexes. Interactions of these lipoproteins with HepG2 cells at 37 degrees C were further examined. These results suggested that HepG2 cells have a specific binding site for apoA-I-containing lipoproteins, and that apoA-I might be a crucial component in the binding of these lipoproteins to human hepatic cells.

Apolipoprotein A-I↗

Fasting plus prandial insulin supplements improve insulin secretory ability in NIDDM subjects.

To examine how insulin secretory ability is modified by strict glycemic control in non-insulin-dependent diabetes mellitus (NIDDM) subjects, basal and/or prandial insulin was supplemented for 4 wk in 24 diabetic subjects who were secondary failures to sulfonylurea treatment. One intermediate-acting insulin injection a day (n = 7) failed to suppress the rise in plasma C-peptide after meals and did not improve plasma C-peptide responses during a posttreatment oral glucose challenge. Continuous subcutaneous insulin infusion with a premeal bolus (n = 8) suppressed both fasting and meal-related rises in C-peptide and improved C-peptide response during the posttreatment oral glucose challenge. Daily insulin requirements during the 4 wk of treatment were reduced significantly by 52%. A short-acting insulin injection before each meal (n = 9) without basal supplementation suppressed the prandial rise in C-peptide and was associated with a significant reduction in daily insulin requirements during 4 wk of treatment by 28%. Diabetic subjects whose fasting and prandial hyperglycemia were less than 140 and less than 200 mg/dl, respectively, showed a significantly higher C-peptide response during oral glucose challenge after treatment than those whose insulin treatment only normalized (less than 200 mg/dl) prandial but not basal hyperglycemia (greater than 140 mg/dl). These results suggest that a short-term period of meal-related insulin treatment (which normalized prandial glycemia) increases residual beta-cell function in NIDDM subjects who failed long-term sulfonylurea administration. A basal insulin supplement alone was not effective. The effectiveness of a prandial insulin supplement may have been further improved by a combined basal and meal-related treatment program.

Acetohexamide↗

The effectiveness of rectal administration of insulin suppository on normal and diabetic subjects.

The effectiveness of insulin administration by rectal suppository was examined in normal and non-insulin-dependent nonobese diabetic subjects. A 100-U insulin suppository (mean 1.8 U/kg) given to the diabetic subjects caused four times as great a fall in plasma glucose compared with the normal subjects given the same dose (mean 1.6 U/kg). The insulin response after suppository administration demonstrated a significantly positive correlation (r = 0.83, P less than 0.01) with the plasma glucose level before administration. Diabetic subjects given a 100-U insulin suppository (mean 1.7 U/kg) 15 min after meals three times daily showed a significant (P less than 0.05) improvement in postprandial hyperglycemia accompanied by a restoration of the normal circadian profile of plasma IRI and a reduction of urinary glucose from 26 +/- 5.9 to 2.0 +/- 1.0 g/day. No untoward reactions were observed. These data strongly imply a unique characteristic of the insulin suppository in spite of low bioavailability.

Adult↗

Telemetry glucose monitoring device with needle-type glucose sensor: a useful tool for blood glucose monitoring in diabetic individuals.

For continuous monitoring of glucose concentration in ambulant diabetic patients, a telemetry glucose monitoring system with a needle-type glucose sensor has been developed. The system consists of a sensor transmitter (4 X 6 X 2 cm, 50 g) that converts current signals generated in a needle-type glucose sensor to high-frequency audio signals and a receiver that continuously calculates glucose concentrations from the received audio signals. The noise range of a monitoring record with the telemetry system (0.3 +/- 0.04%, mean +/- SEM) was significantly smaller than that with a wire-connected system, the wearable artificial endocrine pancreas (2.5 +/- 0.3%). Postprandial tissue glucose concentration responded well to the plasma glucose concentration, with a time lag of 5 min. Continuous glucose monitoring of five diabetic subjects for 77 +/- 22 h revealed that a significant correlation existed between the subcutaneous tissue glucose concentration and the plasma glucose concentration measured simultaneously in each patient. These data indicate the usefulness of the telemetry glucose monitoring system in strict glycemic control of diabetic individuals.

Autoanalysis↗