Azelnidipine, but not amlodipine, reduces urinary albumin excretion and carotid atherosclerosis in subjects with type 2 diabetes: blood pressure control with olmesartan and azelnidipine in Type 2 diabetes (BOAT2 study).

To evaluate the efficacy of azelnidipine and amlodipine on diabetic nephropathy and atherosclerosis, we designed a prospective and randomized controlled clinical study in type 2 diabetic patients with stable glycemic control with fixed dose of anti-diabetic medication. Although there was no difference in blood pressure between both groups, urinary albumin excretion and maximum carotid intima-media thickness were reduced in azelnidipine group, but not in amlodipine group. In addition, inflammatory cytokine levels were decreased only in azelnidipine group which possibly explains such beneficial effects of azelnidipine on urinary albumin excretion and carotid atherosclerosis.

Combination of DPP-4 inhibitor and PPARγ agonist exerts protective effects on pancreatic β-cells in diabetic db/db mice through the augmentation of IRS-2 expression.

We investigated the effects of long- and short-term treatment with pioglitazone (Pio) and/or alogliptin (Alo) on β-cells in diabetic db/db mice. Six-week-old male db/db mice received Pio (25 mg/kg, oral) and/or Alo (30 mg/kg, oral) for 4 weeks and for 2 days. Blood glucose levels were decreased after 4-week intervention, but not after 2-day intervention.

Anti-hypertensive azelnidipine preserves insulin signaling and glucose uptake against oxidative stress in 3T3-L1 adipocytes.

It is known that reactive oxygen species (ROS) are involved in the development of insulin resistance as well as pancreatic β-cell dysfunction both of which are often observed in type 2 diabetes. In this study, we evaluated the effects of azelnidipine, a calcium channel blocker, on ROS-mediated insulin resistance in adipocytes. When 3T3-L1 adipocytes were exposed to ROS, insulin-mediated glucose uptake was suppressed, but such phenomena were not observed in the presence of azelnidipine.

Dietary restriction preserves the mass and function of pancreatic β cells via cell kinetic regulation and suppression of oxidative/ER stress in diabetic mice.

To assess the molecular mechanisms by which dietary restriction preserves the β-cell mass and function in diabetic db/db mice. Male db/db mice were divided into two groups with or without diet restriction. Daily food intake of db/db mice was adjusted to that of the control db/m mice, which was determined in advance.

Protective effects of pioglitazone and/or liraglutide on pancreatic β-cells in db/db mice: Comparison of their effects between in an early and advanced stage of diabetes.

The aim was to compare the protective effects of pioglitazone (PIO) and/or liraglutide (LIRA) on β-cells with the progression of diabetes. Male db/db mice were treated with PIO and/or LIRA for 2 weeks in an early and advanced stage. In an early stage insulin biosynthesis and secretion were markedly increased by PIO and LIRA which was not observed in an advanced stage.

Concomitant use of miglitol and mitiglinide as initial combination therapy in type 2 diabetes mellitus.

Aim: To evaluate the efficacy of miglitol and mitiglinide alone or in combination on the metabolic profile and incretin secretion in Japanese type 2 diabetes patients.

Methods: Patients on diet and exercise with or without metformin, were randomized to receive either miglitol, mitiglinide, or a combination, three times daily for 12 weeks.

Results: At 12 weeks, HbA1c decreased significantly (p<0.

Ablation of 3-phosphoinositide-dependent protein kinase 1 (PDK1) in vascular endothelial cells enhances insulin sensitivity by reducing visceral fat and suppressing angiogenesis.

The phosphatidylinositol 3-kinase signaling pathway in vascular endothelial cells is important for systemic angiogenesis and glucose metabolism. In this study, we addressed the precise role of the 3-phosphoinositide-dependent protein kinase 1 (PDK1)-regulated signaling network in endothelial cells in vivo, using vascular endothelial PDK1 knockout (VEPDK1KO) mice. Surprisingly, VEPDK1KO mice manifested enhanced glucose tolerance and whole-body insulin sensitivity due to suppression of their hepatic glucose production with no change in either peripheral glucose disposal or even impaired vascular endothelial function at 6 months of age.

Self-inducible secretion of glucagon-like peptide-1 (GLP-1) that allows MIN6 cells to maintain insulin secretion and insure cell survival.

Based on the hypothesis that MIN6 cells could produce glucagon-like peptide-1 (GLP-1) to maintain cell survival, we analyzed the effects of GLP-1 receptor agonist, exendin-4 (Ex4), and antagonist, exendin-(9-39) (Ex9) on cell function and cell differentiation. MIN6 cells expressed proglucagon mRNAs and produced GLP-1, which was accelerated by Ex4 and suppressed by Ex9. Moreover, Ex4 further enhanced glucose-stimulated GLP-1 secretion, suggesting autocrine loop-contributed amplification of the GLP-1 signal.

Molecular mechanism by which pioglitazone preserves pancreatic beta-cells in obese diabetic mice: evidence for acute and chronic actions as a PPARgamma agonist.

Pioglitazone preserves pancreatic beta-cell morphology and function in diabetic animal models. In this study, we investigated the molecular mechanisms by which pioglitazone protects beta-cells in diabetic db/db mice. In addition to the morphological analysis of the islets, gene expression profiles of the pancreatic islet were analyzed using laser capture microdissection and were compared with real-time RT-PCR of db/db and nondiabetic m/m mice treated with or without pioglitazone for 2 wk or 2 days.

Gallbladder edema in type 1 diabetic patient due to delayed-type insulin allergy.

A 29-year-old woman was diagnosed as having type 1 diabetes mellitus and received insulin aspart and NPH insulin (NovolinN). On day 22, she had leg edema and right abdominal pain. The serum hepatobiliary enzyme levels were markedly elevated.

Molecular analysis of db gene-related pancreatic beta cell dysfunction; evidence for a compensatory mechanism inhibiting development of diabetes in the db gene heterozygote.

The db gene homozygous, but not heterozygous, mice develop diabetes with severe beta-cell damage. We investigated the molecular mechanism underlying db gene-associated pancreatic beta-cell dysfunction. Islet morphology, beta-cell function, and gene expression profiles specific for pancreatic islet cells were compared among db gene homozygous(db/db), heterozygous (db/m) and unrelated m/m mice.

Effects of sulfonylurea drugs on adiponectin production from 3T3-L1 adipocytes: implication of different mechanism from pioglitazone.

Adiponectin is a fat-derived cytokine with anti-diabetic and anti-atherogenic properties. In this study, effects of sulfonylureas (SUs) on adiponectin production and the action mechanism were evaluated using 3T3-L1 adipocytes. The cells were incubated with glimepiride, glibenclamide, gliclazide, pioglitazone, metformin and the medium only as the control.

Pharmacokinetics and pharmacodynamics of glimepiride in type 2 diabetic patients: compared effects of once- versus twice-daily dosing.

To compare the pharmacokinetic and pharmacodynamic effects of glimepiride between once- and twice-daily dosing in type 2 diabetic patients. Eight Japanese type 2 diabetic patients, who had been treated with 2 mg glimepiride alone over 4 weeks (age 40-70, body mass index View Article and Find Full Text PDF

Effect of apolipoprotein E4 allele on plasma LDL cholesterol response to diet therapy in type 2 diabetic patients.

Objective: The aim of this study was to investigate the effect of apolipoprotein (apo)E4 allele on plasma LDL cholesterol response to calorie-restricted diet therapy in type 2 diabetic patients.

Research Design And Methods: Twenty-four diabetic patients with the apoE3/3 genotype and 11 diabetic patients with the apoE4/3 genotype were recruited. Participants were hospitalized for calorie-restricted diet therapy (25.