Plasma Adiponectin Plays an Important Role in Improving Insulin Resistance With Glimepiride in Elderly Type 2 Diabetic Subjects

Tsunekawa, Taku; Hayashi, Toshio; Suzuki, Yusuke; Matsui-Hirai, Hisako; Kano, Hatsuyo; Fukatsu, Atsushi; Nomura, Noriko; Miyazaki, Asaka; Iguchi, Akihisa

doi:10.2337/diacare.26.2.285

Cited by 112 publications

(81 citation statements)

References 36 publications

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“…In clinical studies, Tsunekawa et al (41) indicated that glimepiride increased plasma adiponectin levels in type 2 diabetic patients, whereas our group and other investigators previously reported that PPAR␥ agonists elevated plasma adiponectin levels in humans (38,42). Thus, the augmenting effect of glimepiride on plasma adiponectin levels in human subjects may be partly accounted for by its PPAR␥ agonist activity.…”

Section: Discussionmentioning

confidence: 77%

Sulfonylurea Agents Exhibit Peroxisome Proliferator-activated Receptor γ Agonistic Activity

Fukuen

Iwaki

Yasui

et al. 2005

Journal of Biological Chemistry

104

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Sulfonylurea (SU) agents, including glimepiride and glibenclamide, are the most widely used oral hypoglycemic drugs, which stimulate insulin secretion primarily by binding to the SU receptor on the plasma membrane of pancreatic ␤-cells. Thiazolidinediones, such as pioglitazone and rosiglitazone, are other hypoglycemic agents that effectively improve peripheral insulin resistance through activation of peroxisome proliferator-activated receptor ␥ (PPAR␥). In the present study, we found that glimepiride specifically induced the transcriptional activity of PPAR␥ in luciferase reporter assays. Glimepiride enhanced the recruitment of coactivator DRIP205 and dissociation of corepressors such as nuclear receptor corepressor and silencing mediator for retinoid and thyroid hormone receptors. In addition, glimepride directly bound to PPAR␥ in a manner competitive to rosiglitazone, which is a proven ligand for PPAR␥. Furthermore, in 3T3-L1 adipocytes, glimepiride stimulated the transcriptional activity of the gene promoter containing PPAR-responsive element and altered mRNA levels of PPAR␥ target genes including aP2, leptin, and adiponectin. Finally, glimepiride induced adipose differentiation in 3T3-F442A cells, which was known to differentiate into adipocytes in a PPAR␥-dependent manner. Most effects observed with glimepiride were also seen with glibenclamide. These data strongly suggest that glimepiride and glibenclamide, both of which belong to SU agents, should have PPAR␥ agonist activity, whose potencies were 16 -25% of the maximum level achieved by pioglitazone. Our observation that glimepiride and glibenclamide could act not only on SU receptor but also on PPAR␥ may give an important clue to the development of novel antidiabetic drugs, which can enhance both insulin secretion from pancreatic ␤-cells and peripheral insulin sensitivity.

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Section: Discussionmentioning

confidence: 77%

Sulfonylurea Agents Exhibit Peroxisome Proliferator-activated Receptor γ Agonistic Activity

Fukuen

Iwaki

Yasui

et al. 2005

Journal of Biological Chemistry

104

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“…These three sulfonylureas may doi: 10.7243/2050-0866-7-1 have different effects on the metabolic system. For example, gliclazide has been demonstrated to directly improve oxidative stress and inflammatory cytokine levels [8,9], whereas glimepiride reportedly promotes glucose uptake at the peripheral tissue level and improves insulin resistance [10]. In other words, presumably sulfonylureas probably lower blood PAI-1 levels by suppressing inflammatory cytokines, oxidative stress, and insulin resistance; however, we hypothesized that the effect of these three sulfonylureas on blood PAI-1 levels could differ depending on the drug (drug-effect).…”

Section: Introductionmentioning

confidence: 79%

Effects of sulfonylurea treatment on blood plasminogen activator inhibitor-1 levels in patients with type 2 diabetes mellitus: A network meta-analysis

Ida¹,

Murata²,

Kaneko³

2018

J Diab Res Clin Met

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Background: To compare the effects ofthree types of sulfonylureas (glibenclamide, gliclazide, and glimepiride) on blood plasminogen activator inhibitor-1 levels in patients with type2 diabetes mellitus, a network meta-analysis of randomized controlled trialswas performed. Methods: A literature search using MEDLINE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov was conducted. Randomized controlled trialsin which the effects of sulfonylureas on blood plasminogen activator inhibitor-1 levels in patients with type 2 diabetes mellitus were evaluated were includes. Outcome assessment included standardized mean differences and 95% confidence intervals. Results: Twelve randomized controlled trials (1,050 subjects) met the inclusion criteria and were included in the network meta-analysis. No significant difference was observedin blood plasminogen activator inhibitor-1 levels after using a placebo compared with those after using glibenclamide, gliclazide, and glimepiride. Blood plasminogen activator inhibitor-1levels were significantly lower after using gliclazide than after using glimepiride (standardized mean difference: -0.52; 95% confidence interval: -0.99%-0.44%). However, no significant difference was observed in blood plasminogen activator inhibitor-1 levels after using glibenclamide compared with those after using gliclazide and glime piride. Conclusions: Regarding the use of sulfonylureas for treating patients with type 2 diabetes mellitus, gliclazide may be preferable because of low blood plasminogen activator inhibitor-1 levels after its use. However, few studies have been published on the use of gliclazide, and the quality of these studies has been generally poor; thus, the results of this study should be interpreted with caution.

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“…Whether the increased p-adiponectin concentration should be considered secondary to improvement in the metabolic syndrome or whether adiponectin has a primary role in this context cannot be concluded from the current study. Although our extended statistical analysis showed that all changes observed in p-adiponectin were related to changes in its covariates, only a randomized study has the utility to clarify whether adiponectin, by decreasing intramyocellular lipid accumulation (24) and hepatic fat content (25), decreases insulin resistance (26,27).…”

Section: Discussionmentioning

confidence: 99%

Plasma adiponectin and serum advanced glycated end-products increase and plasma lipid concentrations decrease with increasing duration of type 2 diabetes

Gottsäter

Szelag²,

Kangro³

et al. 2004

European Journal of Endocrinology

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Objective: To prospectively follow the concentrations of plasma adiponectin (p-adiponectin) and serum advanced glycation end-products (s-AGE) in relation to plasma lipids and retinopathy over 3 years in type 2 diabetic patients. Design and methods: P-adiponectin, s-AGE, plasma lipids and diabetic retinopathy were prospectively evaluated in 61 type 2 diabetic patients at baseline and at follow up 3 years later. Results: Mean p-adiponectin (from 8.84^5.14 to 11.05^6.16 mg/ml; P ¼ 0.006) and s-AGE (from 637^242 to 781^173 ng/ml; P , 0.0001) concentrations had increased at follow up. In addition, HbA1c (7.7^1.7 to 7.4^1.4%; P ¼ 0.0045) and fasting C-peptide (1.00^0.38 to 0.81^0.35 nM; P ¼ 0.019) had decreased and all lipid variables had significantly improved at follow up. P-adiponectin correlated inversely with fasting C-peptide (r s ¼ 20.273; P ¼ 0.045) and low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio (r s ¼ 20.362; P ¼ 0.011), and directly with plasma HDL cholesterol (r s ¼ 0.381; P ¼ 0.005) at follow up. Analysis of variance with adiponectin and s-AGE as dependent variables and fasting C-peptide, plasma HDL and plasma LDL cholesterol as covariates demonstrated that the increase in s-AGE was independent (P ¼ 0.001) and the increase in p-adiponectin dependent on covariate changes (P ¼ 0.862). There was a slight correlation between s-AGE at baseline versus the degree of retinopathy at follow up (r s ¼ 0.281; P ¼ 0.0499).

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Plasma Adiponectin Plays an Important Role in Improving Insulin Resistance With Glimepiride in Elderly Type 2 Diabetic Subjects

Cited by 112 publications

References 36 publications

Sulfonylurea Agents Exhibit Peroxisome Proliferator-activated Receptor γ Agonistic Activity

Sulfonylurea Agents Exhibit Peroxisome Proliferator-activated Receptor γ Agonistic Activity

Effects of sulfonylurea treatment on blood plasminogen activator inhibitor-1 levels in patients with type 2 diabetes mellitus: A network meta-analysis

Plasma adiponectin and serum advanced glycated end-products increase and plasma lipid concentrations decrease with increasing duration of type 2 diabetes

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