Biomedical subjects

R Tohdo

Publications and source records attributed to R Tohdo.

5 recordsLinked to original sources

PubMed1998

Pioglitazone enhances splanchnic glucose uptake as well as peripheral glucose uptake in non-insulin-dependent diabetes mellitus. AD-4833 Clamp-OGL Study Group.

To evaluate the effect of pioglitazone on insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM) patients, a double-blind placebo-controlled trial was carried out with 30 NIDDM patients. Twenty-one subjects, three on diet alone and 18 on sulfonylurea (SU), orally received 30 mg pioglitazone once daily for 12 weeks. Nine subjects, one on diet alone and eight on SU, received a matching placebo once daily for 12 weeks. Euglycemic (5.2 mmol/l) hyperinsulinemic (1200 pmol/l) clamp combined with an oral glucose load (OGL) was performed before and after 3-month treatment with pioglitazone or placebo to determine insulin-stimulated glucose disposal and splanchnic glucose uptake (SGU). No significant differences existed in the patients' characteristics, including age and body mass index, between the two study groups. The pioglitazone treatment increased the mean glucose infusion rate (GIR) prior to OGL from 8.2 +/- 2.2 to 9.2 +/- 2.0 mg/kg.min (mean +/- SD, P = 0.003) and increased the SGU rate from 28.5 +/- 19.4 to 59.4 +/- 27.1% (P = 0.010). The placebo treatment produced no significant changes in either GIR or SGU after treatment. A significant difference (P = 0.042) was observed in change of SGU between the pioglitazone and placebo treatment groups. In conclusion, the results indicate that pioglitazone is effective for ameliorating insulin resistance in NIDDM by enhancing SGU as well as peripheral glucose uptake.

Blood Glucose↗

PubMed1998

High plasma free fatty acids decrease splanchnic glucose uptake in patients with non-insulin-dependent diabetes mellitus.

It has been proposed that high plasma free fatty acid (FFA) levels observed in patients with non-insulin dependent diabetes mellitus (NIDDM) contribute to the development of their insulin resistance. We examined patients with NIDDM to find whether maintaining plasma FFA levels in the fasting range with a euglycemic hyperinsulinemic clamp combined with an oral glucose load (clamp OGL) would affect insulin-mediated peripheral glucose uptake (PGU) and splanchnic glucose uptake (SGU). Nine NIDDM subjects (age, 55 +/- 3 years; duration of diabetes, 11 +/- 2 years; body mass index, 21.0 +/- 0.4 kg/m2; hemoglobin A1c, 9.0 +/- 0.3%; fasting plasma glucose, 9.4 +/- 3.0 mmol/l, means +/- SEM) were hospitalized and treated with diet, oral hypoglycemic agents or insulin for at least 2 weeks to maintain fasting plasma glucose < 8 mmol/l. All the patients were subjected to two different protocols in a random order. On one protocol, under the hyperinsulinemic condition, FFAs were maintained at the their fasting levels (1.19 +/- 0.08) by triglyceride emulsion infusion (Lipid infusion study, L), and on the other protocol, FFAs were made to fall (0.26 +/- 0.06 mmol/l) with saline instead of triglyceride emulsion infusion (Saline infusion study, S). During euglycemic (L, 5.4 +/- 0.2; S, 5.1 +/- 0.2 mmol/l) hyperinsulinemic (L, 1377 +/- 108; S, 1328 +/- 67 pmol/l) clamp, high FFA levels significantly reduced PGU (L, 26.7 +/- 3.6; S, 32.1 +/- 3.4 mumol.kg-1.min-1, P < 0.05) and SGU (L, 12.1 +/- 4.2; S, 27.5 +/- 5.6%, P < 0.05). In conclusion, high FFA levels in patients with NIDDM impaired insulin-mediated glucose uptake in the splanchnic as well as peripheral tissues.

3-Hydroxybutyric Acid↗

PubMed1989

Simultaneous evaluation of insulin secretion and action using a model.

For the simultaneous evaluation of insulin secretion and insulin sensitivity, a glucose regulation model has been developed. In order to estimate the parameters of the model, an intravenous glucose infusion test (GIT, 100 mg/kg.min x 2 min and 10 mg/kg.min x 118 min) was carried out on 15 healthy subjects (N), 12 subjects with impaired glucose tolerance (IGT), 20 non-insulin-dependent diabetics (NIDDM) and 13 patients with chronic pancreatitis (CP). The coefficient (microU/mg) for insulin secretion depending on blood glucose concentration in IGT, NIDDM and CP were lower (35.9 +/- 2.7, 24.5 +/- 3.3, 43.1 +/- 3.1) than in N (77.5 +/- 7.9). The coefficients (microU.min/mg) for insulin secretion depending on rate of change in blood glucose concentration in IGT and NIDDM were significantly lower (6.5 +/- 2.1, 3.8 +/- 1.2) than in N (52.8 +/- 8.8). The insulin sensitivity index (ISI; 10(-2) mg/(microU/ml).kg.min) in NIDDM was lower (4.98 +/- 0.75) than in N (11.37 +/- 1.08). Administration of exogenous insulin did not significantly affect the value of ISI in N and NIDDM. ISI showed a tendency to increase (15.09 +/- 1.92) in CP. It was demonstrated that the proposed model which estimates both insulin secretory ability and insulin sensitivity simultaneously is quite useful for analyzing the mechanism of impaired glucose tolerance.

Adult↗

PubMed1979

Counterregulatory system in an artificial endocrine pancreas. Glucose infusion algorithm.

An artificial endocrine pancreas has been developed by adding a glucose infusion system to the artificial beta cell system. In this computer algorithm, glucose is infused on the basis of proportional and derivative actions to blood glucose concentration with the time delay constant between blood withdrawal and initiation of glucose infusion. When glucose was infused on the basis of proportional action with a 20-minute time delay, the prompt restoration to normoglycemia from the hypoglycemic state with a smaller amount of glucose was shown in depancreatized dogs. These results indicate that the artificial endocrine pancreas thus prepared is not only a useful device to safely control blood glucose, but also is an efficient research tool for the analysis of the blood glucose regulatory mechanism.

Animals↗

PubMedDate not supplied

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↗