Coenzyme Q10 suppresses apoptosis of mouse pancreatic beta-cell line MIN6

Background: In mitochondrial diabetes, apoptosis of β-cells caused by mitochondrial stress plays an important role in impaired insulin secretion. Several studies have reported that coenzyme Q10 (CoQ10) has therapeutic effects on mitochondrial diabetes, but no reports have examined the fundamental effectiveness or mechanism of CoQ10 in mitochondrial diabetes. We previously reported in a Japanese article that CoQ10 has protective effects on pancreatic β-cells against mitochondrial stress using mouse pancreatic β-cell line MIN6 and staurosporine (STS). Here, we report that CoQ10 protects MIN6 cells against apoptosis caused by STS and describe the more detailed apoptotic cascade. Methods: Apoptosis of MIN6 cells was induced by 0.5 μM STS treatment for specific periods with or without 30 μM CoQ10. The apoptosis cascade in MIN6 cells was then investigated using WST-8 assays, annexin-V staining, western blotting, and DNA degradation analysis. Results: Sixteen hours of 0.5 μM STS treatment led to 47% cell viability, but pretreatment with 30 μM CoQ10 resulted in significantly higher viability of 76% (P < 0.01). CoQ10 also prevented translocation of phosphatidylserine from the inner leaflet to the outer leaflet of the cell membrane. CoQ10 prevented cytochrome c release from mitochondria and activation of caspase-3. Conclusion: We concluded that CoQ10 protects pancreatic β-cells through anti-apoptotic effects against STS treatment

Bone Regeneration in Artificial Jaw Cleft by Use of Carbonated Hydroxyapatite Particles and Mesenchymal Stem Cells Derived from Iliac Bone

Objectives of the Study. Cleft lip and palate (CLP) is a prevalent congenital anomaly in the orofacial region. Autogenous iliac bone grafting has been frequently employed for the closure of bone defects at the jaw cleft site. Since the related surgical procedures are quite invasive for patients, it is of great importance to develop a new less invasive technique. The aim of this study was to examine bone regeneration with mesenchyme stem cells (MSCs) for the treatment of bone defect in artificially created jaw cleft in dogs. Materials and Methods. A bone defect was prepared bilaterally in the upper incisor regions of beagle dogs. MSCs derived from iliac bone marrow were cultured and transplanted with carbonated hydroxyapatite (CAP) particles into the bone defect area. The bone regeneration was evaluated by standardized occlusal X-ray examination and histological observation. Results. Six months after the transplantation, perfect closure of the jaw cleft was achieved on the experimental side. The X-ray and histological examination revealed that the regenerated bone on the experimental side was almost equivalent to the original bone adjoining the jaw cleft. Conclusion. It was suggested that the application of MSCs with CAP particles can become a new treatment modality for bone regeneration for CLP patients

Normal meal tolerance test is preferable to the glucagon stimulation test in patients with type 2 diabetes that are not in a hyperglycemic state: Comparison with the change of C-peptide immunoreactivity

Aims/Introduction: The aim of the present study was to evaluate the properties of the glucagon stimulation test (GST) and the normal meal tolerance test (NMTT) in patients with type 2 diabetes. Materials and Methods: We enrolled 142 patients with type 2 diabetes, and carried out a GST and a NMTT. We carried out the NMTT using a calorie-controlled meal based on an intake of 30 kcal/kg ideal bodyweight/day. We calculated the change in C-peptide immunoreactivity (ΔCPR) by subtracting fasting CPR from the CPR 6 min after the 1-mg glucagon injection (GST) or 120 min after the meal (NMTT). Results: Mean ΔCPR for the GST was 2.0 ng/mL, and for the NMTT was 3.1 ng/mL. A total of 104 patients had greater ΔCPR in the NMTT than the GST, and the mean ΔCPR was significantly greater in the NMTT than the GST (P < 0.05). To exclude any influence of antidiabetic drugs, we examined 42 individuals not taking antidiabetic agents, and found the mean ΔCPR was significantly greater in the NMTT than the GST (GST 2.4 ng/mL, NMTT 4.3 ng/mL; P < 0.05). To consider the influence of glucose toxicity, we carried out receiver operating characteristic analyses with fasting plasma glucose and glycated hemoglobin. The optimal cut-off levels predicting GST ΔCPR to be larger than NMTT ΔCPR were fasting plasma glucose 147 mg/dL and glycated hemoglobin 9.0% (fasting plasma glucose: sensitivity 0.64, specificity 0.76, area under the curve 0.73; glycated hemoglobin: sensitivity 0.56, specificity 0.71, area under the curve 0.66). Conclusions: The NMTT is a reliable insulin secretion test in patients with type 2 diabetes, except for those in a hyperglycemic state

High Serum Advanced Glycation End Products Are Associated with Decreased Insulin Secretion in Patients with Type 2 Diabetes: A Brief Report

Advanced glycation end products (AGEs) are important in the pathophysiology of type 2 diabetes mellitus (T2DM). They directly cause insulin secretory defects in animal and cell culture models and may promote insulin resistance in nondiabetic subjects. We have developed a highly sensitive liquid chromatography-tandem mass spectrometry method for measuring AGEs in human serum. Here, we use this method to investigate the relationship between AGEs and insulin secretion and resistance in patients with T2DM. Methods. Our study involved 15 participants with T2DM not on medication and 20 nondiabetic healthy participants. We measured the AGE carboxyethyllysine (CEL), carboxymethyllysine (CML), and methyl-glyoxal-hydro-imidazolone (MG-H1). Plasma glucose and insulin were measured in these participants during a meal tolerance test, and the glucose disposal rate was measured during a euglycemic-hyperinsulinemic clamp. Results. CML and CEL levels were significantly higher in T2DM than non-DM participants. CML showed a significant negative correlation with insulin secretion, HOMA-%B, and a significant positive correlation with the insulin sensitivity index in T2DM participants. There was no correlation between any of the AGEs measured and glucose disposal rate. Conclusions. These results suggest that AGE might play a role in the development or prediction of insulin secretory defects in type 2 diabetes

Body mass index >= 23 is a risk factor for insulin resistance and diabetes in Japanese people: A brief report

Background: Screening for undiagnosed type 2 diabetes mellitus is recommended for Asian Americans with a body mass index ≥23. However, the optimal body mass index cut-off score for predicting the risk of diabetes mellitus in Japanese people is not well known. The aim of this study was to determine the best body mass index cut-off score for predicting insulin resistance and diabetes mellitus in the Japanese population. Methods: This study had two parts, a clinical investigation and a retrospective observational investigation. In the clinical part of the study, 58 participants (26 with type 2 diabetes mellitus and 32 non-diabetics) underwent a hyperinsulinemic-euglycemic clamp from which their glucose disposal rate was measured. For the retrospective part of the study, medical check-up data from 88,305 people in the Tottori Prefecture were analyzed for clinical evidence of diabetes mellitus. The optimal BMI cut-off scores for prediction of insulin resistance and diabetes mellitus were determined. Results: In the clamp study, the optimal body mass index cut-off score to predict insulin resistance in non-diabetic patients was 22.7. All participants with type 2 diabetes mellitus were insulin resistant, and the optimal body mass index cut-off score for prediction of severe insulin resistance was 26.2. When the data from the type 2 diabetic and the non-diabetic participants were combined, the optimal body mass index cut-off score for prediction of insulin resistance was 23.5. Analysis of 88,305 medical check-up records yielded an optimal body mass index cut-off score for prediction of diabetes mellitus of 23.6. Conclusions: These results suggest that having a body mass index ≥23 is a risk factor for insulin resistance and diabetes mellitus in the Japanese population

CPR-IR is an insulin resistance index that is minimally affected by hepatic insulin clearance-A preliminary research

Background: Increased hepatic insulin clearance (HIC) is important in the pathophysiology of type 2 diabetes mellitus (T2DM). The aim of this study is to analyze an effective insulin resistance (IR) index that is minimally affected by HIC. Methods: Our study involved 20 participants with T2DM and 21 healthy participants without diabetes (Non-DM). Participants underwent a meal tolerance test from which plasma glucose, insulin and serum C-peptide immunoreactivity (CPR) were measured, and HOMA-IR and HIC were calculated. Participants then underwent a hyperinsulinemic-euglycemic clamp from which the glucose disposal rate (GDR) was measured. Results: The index CPR-IR = 20/(fasting CPR × fasting plasma glucose) was correlated more strongly with GDR, than was HOMA-IR, and CPR-IR could be used to estimate GDR. In T2DM participants with HIC below the median, HOMA-IR and CPR-IR were equally well correlated with GDR. In T2DM with high HIC, CPR-IR correlated with GDR while HOMA-IR did not. In Non-DM, CPR-IR and HOMA-IR were equally well correlated with GDR regardless of HIC. The mean HIC value in T2DM was significantly higher than that of Non-DM. Conclusions: CPR-IR could be a simple and effective index of insulin resistance for patients with type 2 diabetes that is minimally affected by HIC

Screening Criteria of Diabetes Mellitus and Impaired Glucose Tolerance of the Japanese Population in a Rural Area of Japan: The Tottori-Kofu Study

We performed the Tottori-Kofu Study to develop an early detection method of the Japanese with diabetes mellitus (DM) and impaired glucose tolerance (IGT), using simple predictors such as fasting plasma glucose (FPG) and other risk information obtainable from basic medical check-ups. In 2005, 734 residents of Kofu Town received a basic medical check-up including blood examination. Some of them meeting the following criteria further underwent the oral glucose tolerance test (OGTT): 5.5 mmol/L (100 mg/dL) ? FPG < 7.0 mmol/L (126 mg/dL); or FPG < 5.5 mmol/L, HbA1c ? 5.5%, BMI ? 25 kg/m2, triglyceride ? 1.69 mmol/L (150 mg/dL), hypertension treatment and family history of DM. Among the 734, only 4 persons with FPG ? 7.0 mmol/L were newly diagnosed as having DM, and 17 persons with FPG ? 6.1 mmol/L (110 mg/dL) were diagnosed with impaired fasting glucose. Among 220 persons who received the OGTT, 115 had normal glucose tolerance, 85 had IGT and 20 had DM. When the above-mentioned criteria were added to FPG levels, additional 67 persons with abnormal glucose tolerance were found. The optimal level to detect IGT and DM was 5.2 mmol/L (93 mg/dL) for FPG and 5.3% for HbA1c. Of persons only with the single risk factor of hypertension treatment, 39.3% had IGT. In conclusion, the results indicate that FPG of 5.2 mmol/L (93 mg/dL), HbA1c of 5.3% and hypertension treatment are useful in detecting early stages of IGT and DM

Screening Criteria of Diabetes Mellitus and Impaired Glucose Tolerance of the Japanese Population in a Rural Area of Japan: The Tottori-Kofu Study

We performed the Tottori-Kofu Study to develop an early detection method of the Japanese with diabetes mellitus (DM) and impaired glucose tolerance (IGT), using simple predictors such as fasting plasma glucose (FPG) and other risk information obtainable from basic medical check-ups. In 2005, 734 residents of Kofu Town received a basic medical check-up including blood examination. Some of them meeting the following criteria further underwent the oral glucose tolerance test (OGTT): 5.5 mmol/L (100 mg/dL) ? FPG < 7.0 mmol/L (126 mg/dL); or FPG < 5.5 mmol/L, HbA1c ? 5.5%, BMI ? 25 kg/m2, triglyceride ? 1.69 mmol/L (150 mg/dL), hypertension treatment and family history of DM. Among the 734, only 4 persons with FPG ? 7.0 mmol/L were newly diagnosed as having DM, and 17 persons with FPG ? 6.1 mmol/L (110 mg/dL) were diagnosed with impaired fasting glucose. Among 220 persons who received the OGTT, 115 had normal glucose tolerance, 85 had IGT and 20 had DM. When the above-mentioned criteria were added to FPG levels, additional 67 persons with abnormal glucose tolerance were found. The optimal level to detect IGT and DM was 5.2 mmol/L (93 mg/dL) for FPG and 5.3% for HbA1c. Of persons only with the single risk factor of hypertension treatment, 39.3% had IGT. In conclusion, the results indicate that FPG of 5.2 mmol/L (93 mg/dL), HbA1c of 5.3% and hypertension treatment are useful in detecting early stages of IGT and DM