Yoshinori Satoh

The effects of coenzyme Q10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A to G) mutation

Summary The characteristic clinical features of diabetes mellitus with mitochondrial DNA (mtDNA) 3243(A-G) mutation are progressive insulin secretory defect, neurosensory deafness and maternal inheritance, referred to as maternally inherited diabetes mellitus and deafness (MIDD). A treatment for MIDD to improve insulin secretory defects and reduce deafness has not been established. The effects of coenzyme Q10 (CoQ10) treatment on insulin secretory response, hearing capacity and clinical symptoms of MIDD were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant subjects with impaired glucose tolerance (IGT), and 15 mutant subjects with normal glucose tolerance (NGT) were treated daily with oral administration of 150 mg of CoQ10 for 3 years. Insulin secretory response, blood lactate after exercise, hearing capacity and other laboratory examinations were investigated every year. In the same way we evaluated 16 MIDD patients (control-DM), 5 mutant IGT and 5 mutant NGT subjects in yearly examinations. The insulin secretory response assessed by glucagon-induced C-peptide secretion and 24 h urinary C-peptide excretion after 3 years in the CoQ10-DM group was significantly higher than that in the control-DM group. CoQ10 therapy prevented progressive hearing loss and improved blood lactate after exercise in the MIDD patients. CoQ10 treatment did not affect the diabetic complications or other clinical symptoms of MIDD patients. CoQ10 treatment did not affect the insulin secretory capacity of the mutant IGT and NGT subjects. There were no side effects during therapy. This is the first report demonstrating the therapeutic usefulness of CoQ10 on MIDD. [Diabetologia (1998) 41: 584–588]

Urinary chiro-Inositol Excretion is an Index Marker of Insulin Sensitivity in Japanese Type II Diabetes

OBJECTIVE To determine the relationship between urinary chiro-inositol excretion and insulin sensitivity in Japanese type II diabetic patients. RESEARCH DESIGN AND METHODS Eighteen subjects were age-matched, nonobese, type II diabetic patients. Eight subjects had impaired glucose tolerance (IGT), and 10 had normal glucose tolerance (NGT). We quantified urinary chiro-inositol excretion using gas chromatography-mass spectrometry and the insulin sensitivity index (SI), and glucose effectiveness (SG) using Bergmans modified minimal model method. RESULTS The urinary excretion of chiro-inositol was much lower in the diabetic patients (32.3 ± 16.0 μmol/day, means ± SD) than in the NGT subjects (96.0 ± 17.6; P < 0.0001) and IGT subjects (58.9 ± 11.6; P < 0.0001). SI was much lower in the diabetic patients (3.81 ± 1.49) than in the NGT subjects 6.30 ± 1.59, P < 0.0005). SG was much lower in the diabetic patients (2.14 ± 0.56) than in the NGT subjects (3.07 ± 0.38, P < 0.0001). There was a significant correlation between urinary chiro-inositol excretion and SI (r = 0.766), as well as a significant correlation between urinary chiro-inositol excretion and SG (r = 0.747). CONCLUSIONS There is a direct relationship of urinary chiro-inositol excretion to insulin sensitivity and SG in humans. Urinary chiro-inositol excretion might be useful as a metabolic index of insulin sensitivity in type II diabetes.

Pancreatic beta-cell secretory defect associated with mitochondrial point mutation of the tRNALEU(UUR) gene: a study in seven families with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS)

SummaryRecent evidence suggests possible linkage between diabetes mellitus and mitochondrial gene mutation. We surveyed mitochondrial tRNALEU(UUR) (3243) mutation in 7 mitochondrial encephalomyopathy, lactic acidosis and stroke-like episode (MELAS) families and identified 24 mutated subjects (7 MELAS probands and 17 non-MELAS relatives) as well as 11 non-mutant family members. An OGTT in the 24 mutant relatives revealed 14 diabetic subjects, 3 with impaired glucose tolerance and 7 with normal glucose tolerance and all non-mutant family members as having normal glucose tolerance. Insulinogenic index was significantly reduced in the mutant diabetic subjects and those with impaired and normal glucose tolerance in comparison with the normal control subjects and the non-mutant members. Urinary 24-h C-peptide immunoreactivity excretion was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance, compared with the control subjects and the non-mutant family members. Plasma C-peptide immunoreactivity 6 min after glucagon injection was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance compared with the control subjects and the non-mutant family members. Si, an index of insulin sensitivity of the four mutant subjects was within normal range. Islet cell antibodies were negative in sera of eight mutated diabetic subjects, 2 and 6 with impaired and normal glucose tolerance, respectively. Diabetic retinopathy and nephropathy were demonstrated in 7 (50%) and 12 (85.7%) of 14 mutant diabetic subjects, respectively. Neurosensory deafness was demonstrated in 12 (85.7%) of 14 mutated diabetic subjects, (66.7%) of 3 mutated impaired glucose tolerant subjects, but not detected in 6 mutated normal glucose tolerant subjects and 11 non-mutant family members. These findings suggest that the tRNALEU(UUR) mutation is associated with pancreatic beta-cell secretory defect of insulin.

Diabetes With Mitochondrial Gene tRNALYS Mutation

OBJECTIVE To solve a possible relationship between mtDNA mutation of tRNALYS(8344) and diabetes, we have surveyed the tRNALYS mutation, glucose intolerance, and insulin secretory capacity in a Japanese family with diabetes and myoclonic epilepsy with ragged-red fiber disease. Several lines of evidence suggested possible linkage between mtDNA mutation and diabetes (1–4). RESEARCH DESIGN AND METHODS DNA was isolated from peripheral lymphocytes. The polymerase chain reaction analysis for the tRNALYS(8344) mutation of the mtDNA was conducted as described by Larsson (5). Insulin secretory capacity was assessed by 24-h urinary C-peptide immunoreactivity response (CPR) excretion and plasma CPR to glucagon administration. RESULTS We identified seven subjects with the tRNALYS mutation as well as seven non-mutated members in the pedigrees. Oral glucose tolerance tests in the pedigree indicated that five of the mutated subjects were diabetic, one had impaired glucose tolerance, and one had normal glucose tolerance (NGT), whereas all nonmutated family members had NGT. The pedigree shows maternal transmission of diabetes and the tRNALYS mutation over three generations. Twenty-four-hour urinary excretion of CPR was significantly reduced in the mutant subjects (mean ± SD, 67.8 ± 79.2 nmol/day, n = 6, P < 0.001) compared with the nonmutant members (276.6 ± 41.8 nmol/day, n = 5) and the age-matched normal control subjects (263 ± 64.3 nmol/day, n = 12). Plasma CPR 6 min after glucagon injection demonstrated a marked reduction in the mutant subjects (3.68 ± 3.45 nmol/l, n = 5, P < 0.001) compared with the nonmutant members (19.4 ± 1.17 nmol/l, n = 5) and the normal control subjects (15.8 ± 3.81 nmol/l, n = 12). Bilateral neurosensory deafness was demonstrated in five of seven (71.4%) mutant subjects (five of five [100%] mutated diabetic patients), but not detected in six nonmutant members. CONCLUSIONS This observation is the first report of association of diabetes with the mitochondrial tRNALYS mutation. Insulin secretory capacity was significantly lower in the mutant members than in the nonmutated members. These findings suggest that the pancreatic β-cell secretory defect of insulin might be one of the phenotypes of the mitochondrial tRNALYS mutation.

A color-based tracking by Kalman particle filter

In this paper, a method for real-time tracking of moving objects is proposed. We applied Kalman particle filter (KPF) to color-based tracking. This KPF is a particle filter including the principle of Kalman filter, and it was adopted to the object contour tracking. We modified this KPF for color-based tracking. This modified KPF can approximate the probabilistic density of the position of the tracked object properly and needs fewer particles for tracking than conventional particle filters. We made experiments to confirm the effectiveness of this method.

Effect of manidipine and delapril on insulin sensitivity in type 2 diabetic patients with essential hypertension

The open trial was designed to evaluate the effects of long-term antihypertensive treatment with the calcium-channel blocker, manidipine and the angiotensin converting enzyme (ACE) inhibitor, delapril on insulin sensitivity in Japanese non-insulin dependent diabetes mellitus (NIDDM) patients with essential hypertension. We measured the insulin sensitivity index (SI) and the glucose-effectiveness (SG) by the use of Bergmans minimal model method in 18 hypertensive NIDDM patients before and after administration of manidipine (group A) or delapril (group B) for 3 months. Manidipine treatment for 3 months significantly improved SI in group A from 3.35 +/- 0.61 (x 10(-4) min-1 microU-1 ml-1) to 4.70 +/- 1.34 (P < 0.05). Delapril treatment for 3 months also significantly improved SI in group B from 3.56 +/- 1.04 to 5.00 +/- 0.87 (P < 0.05). Manidipine significantly improved SG in group A from 1.60 +/- 0.64 (x 10(-2) min) to 2.19 +/- 0.38 (P < 0.05). Delapril treatment also significantly improved SG in the group B from 1.41 +/- 0.56 to 1.91 +/- 0.35 (P < 0.05). Manidipine and delapril did not affect urinary C-peptide excretion for 24 h in the hypertensive NIDDM patients. Treatment with manidipine or delapril significantly reduced systolic and diastolic blood pressures in the hypertensive NIDDM patients. There were no differences between plasma glucose, serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions, heart rate and body weight after 3 months on manidipine or delapril. This study confirmed the improving effects on SI and SG by long-term treatment with manidipine or delapril in the hypertensive NIDDM patients.

Insulin Stimulates Hydrolysis of Plasmanylinositol-Glycan and Phosphatidylinositol-Glycan in Rat Adipocytes: Insulin-Induced Generation of Inositol Glycan, Alkylacylglycerol, and Diacylglycerol

Insulin binding to its receptor has been known to induce hydrolysis of phosphatidylinositol-glycan and release inositol-glycan and diacylglycerol, two putative second messengers of insulin actions. We metabolically labeled and purified PIG in rat cultured adipocytes. The treatment of [3H]glycerol-labeled PIG with phosphatidylinositol-specific phospholipase C released [3H]glycerol-labeled DAG and [3H]glycerol-labeled 1-alkyl,2-acyl-glycerol, suggesting that PIG has not only PIG but also plasmanylinositol-glycan moiety. Insulin induced hydrolysis of PIG/PMIG and generation of IG, DAG, and AAG in a dose-dependent manner. This report shows the first demonstration of insulin-sensitive PMIG in rat adipocytes. These results provide evidence that insulin-induced generation of IG, DAG, and AAG might be early events in the insulin-signaling mechanism in rat adipocytes, and insulin-releasable AAG seems to mediate some actions of insulin.

The effects of amylin on insulin secretion from Rin m5F cells and glycogen synthesis and lipogenesis in rat primary cultured hepatocytes

The purpose of the study was to determine the physiological actions of amylin, a novel 37-amino acid peptide isolated from pancreatic islet amyloid deposits. Our results showed that an infusion of amylin reduced fasting plasma insulin levels and impaired glucose tolerance in mice. Amylin significantly reduced insulin secretion in rat insulinoma cell lines (Rin m5F cells) that were stimulated by either isoproterenol and forskolin, but it did not affect insulin secretion stimulated by isobutyl-methylxanthine (IBMX) or dibutyryl cyclic-adenosine monophosphate (db-cAMP). Amylin also reduced cAMP levels in Rin m5F cells in response to isoproterenol, but did not affect cAMP levels in cells pretreated with pertussis toxin. These results suggest that the reduction of cAMP by amylin may be mediated through pertussis toxin-sensitive Gi proteins. Amylin significantly reduced basal and insulin-stimulated glycogen synthesis in rat primary cultured hepatocytes. Amylin stimulated basal and insulin-stimulated lipogenesis in hepatocytes. Amylin did not affect DNA synthesis in hepatocytes. These results suggest that amylin conducts dispersion actions on in vivo glucose metabolism in rat, and in vitro insulin secretion from Rin m5F cells and metabolism in rat hepatocytes.

A color-based probabilistic tracking by using graphical models

In this paper, a method for real-time tracking of moving objects or pedestrians is proposed. Especially, we tackled to track an object whose part was temporally occluded or which traversed in front of the cluttered background. Furthermore, we tried to obtain the accurate trajectory of the center of it stably even then. For the problems, we present a probabilistic color-based tracking. In our proposed method, we incorporated particle filtering into graphical models and applied it to the color-based tracking. When the color histogram of the tracked object was made, we used not one region of the whole of the object but the multi-part region of it if it was divided in some parts (e.g. the head and the body of a pedestrian). We treated the multi-part region as a graphical model. In the graphical model, messages about the state of the parts are sent to other parts. As the result., even when the tracked object has occluded part, our proposed method can track it stably and infer the state (e.g. position) of the occluded part. We made experiments to confirm effectiveness of this proposed method.

Binocular motion tracking by gaze fixation control and three-dimensional shape reconstruction

It is an easy task for the human visual system to gaze continuously at an object moving in three-dimensional (3-D) space. While tracking the object, human vision seems able to comprehend its 3-D shape with binocular vision. We conjecture that, in the human visual system, the function of comprehending the 3-D shape is essential for robust tracking of a moving object. In order to examine this conjecture, we constructed an experimental system of binocular vision for motion tracking. The system is composed of a pair of active pan-tilt cameras and a robot arm. The cameras are for simulating the two eyes of a human while the robot arm is for simulating the motion of the human body below the neck. The two active cameras are controlled so as to fix their gaze at a particular point on an object surface. The shape of the object surface around the point is reconstructed in real-time from the two images taken by the cameras based on the differences in the image brightness. If the two cameras successfully gaze at a single point on the object surface, it is possible to reconstruct the local object shape in real-time. At the same time, the reconstructed shape is used for keeping a fixation point on the object surface for gazing, which enables robust tracking of the object. Thus these two processes, reconstruction of the 3-D shape and maintaining the fixation point, must be mutually connected and form one closed loop. We demonstrate the effectiveness of this framework for visual tracking through several experiments.