scholarly journals A novel 11β-HSD1 inhibitor improves diabesity and osteoblast differentiation

2014 ◽  
Vol 52 (2) ◽  
pp. 191-202 ◽  
Author(s):  
Ji Seon Park ◽  
Su Jung Bae ◽  
Sik-Won Choi ◽  
You Hwa Son ◽  
Sung Bum Park ◽  
...  

Selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have considerable potential as treatment for osteoporosis as well as metabolic syndrome including type 2 diabetes mellitus. Here, we investigated the anti-diabetic, anti-adipogenic, and anti-osteoporotic activity of KR-67500, as a novel selective 11β-HSD1 inhibitor. Cellular 11β-HSD1 activity was tested based on a homogeneous time-resolved fluorescence method. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) levels were measured in diet-induced obese (DIO)-C57BL/6 mice administered KR-67500 (50 mg/kg per day, p.o.) for 28 days and, additionally, its anti-diabetic effect was evaluated by OGTT and ITT. Thein vitroanti-adipogenic effect of KR-67500 was determined by Oil Red O Staining. Thein vitroanti-osteoporotic activity of KR-67500 was evaluated using bone morphogenetic protein 2 (BMP2)-induced osteoblast differentiation and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation model systems. KR-67500 improved thein vivoglucose tolerance and insulin sensitivity in DIO-C57BL/6 mice. KR-67500 suppressed cortisone-induced differentiation of 3T3-L1 cells into adipocytes. KR-67500 enhanced BMP2-induced osteoblastogenesis in C2C12 cells and inhibited RANKL-induced osteoclastogenesis in mouse bone marrow-derived macrophages. KR-67500, a new selective 11β-HSD1 inhibitor, may provide a new therapeutic window in the prevention and/or treatment of type 2 diabetes, obesity, and/or osteoporosis.

2014 ◽  
Vol 60 (1) ◽  
pp. 32-35
Author(s):  
E A Shestakova ◽  
A V Ilyin ◽  
A D Deev ◽  
M V Shestakova ◽  
I I Dedov

The study included 127 patients with type 2 diabetes (T2D) risk factors, who underwent oral glucose tolerance test (75 g glucose) with pancreatic and incretin hormones estimated in fasting state, at 30 and 120 minutes after glucose load. According to the test results the population was divided into 3 groups: group with normal glucose tolerance (NGT), group with high risk of diabetes developing (impaired glucose tolerance (IGT) and impaired fasting glycemia (IFG)) and newly-diagnosed T2D. The stimulated glucagon secretion was suppressed in NGT group, whereas in T2D patients there was an increase in glucagon levels at 30 min after the glucose load. Within high risk group the area under curve (AUC) of glucagon secretion was significantly elevated in IFG patients comparing to IGT (0,52 vs 0,07 ng·ml-1·min-1, р=0,0005). AUC of glucagon secretion was positively related only to fasting glucagon-like peptide 2 (GLP-2) level (r=0,61, р=0,0001), that suggests glucagonotropic properties for GLP-2. We conclude that glucagon stimulation by GLP-2 may play a role in decreased glucagon suppression in T2D patients and IFG state development.


Diabetes Care ◽  
2000 ◽  
Vol 23 (9) ◽  
pp. 1440-1441 ◽  
Author(s):  
M. Stumvoll ◽  
A. Mitrakou ◽  
W. Pimenta ◽  
T. Jenssen ◽  
H. Yki-Jarvinen ◽  
...  

Author(s):  
VV Boeva ◽  
TA Boeva ◽  
AN Zavyalov

In order to assess the diagnosis of carbohydrate metabolism disorders, day care patients from Tambov central regional hospital were investigated. The study was conducted during 6 months in 2018. The study included 91 patients and allowed the diagnosis of type 2 diabetes mellitus (DM) in 31 (34.0%) cases, 6 (6.5%) impaired fasting glucose and 22 (24.1%) impaired glucose tolerance. This survey highlighted the necessity to expand the screening populations at risk for developing type 2 diabetes. The rational for the 75-gram oral glucose tolerance test for all individuals with fasting plasma glucose ≥ 5.6 ≤ 6.0 mmol/l and having one or more risk factors for developing type 2 diabetes and / or metabolic syndrome is shown. Among these categories diabetes was detected in 4.3%, and prediabetes in 14.4% of cases.


2020 ◽  
Vol 17 (3) ◽  
pp. 147916412092212
Author(s):  
Giulia Ferrannini ◽  
Elisabet Svenungsson ◽  
Barbro Kjellström ◽  
Kerstin Elvin ◽  
Giorgia Grosso ◽  
...  

Background: Cardiovascular disease is a serious complication in patients with dysglycaemia, defined as either type 2 diabetes or impaired glucose tolerance. Research focusing on the identification of potential markers for atherothrombotic disease in these subjects is warranted. The antiphospholipid syndrome is a common acquired prothrombotic condition, defined by a combination of thrombotic events and/or obstetric morbidity and positivity of specific antiphospholipid antibodies. Available information on antiphospholipid antibodies in dysglycaemia is scarce. Objective: This study investigates the association between antiphospholipid antibodies and dysglycaemia. Patients/Methods: The PAROKRANK (periodontitis and its relation to coronary artery disease) study included 805 patients, investigated 6–10 weeks after a first myocardial infarction, and 805 matched controls. Participants without known diabetes (91%) underwent an oral glucose tolerance test. Associations between antiphospholipid antibodies (anti-cardiolipin and anti-β2 glycoprotein-I IgG, IgM and IgA) and dysglycaemia were analysed. Results: In total, 137 (9%) subjects had previously known type 2 diabetes and 371 (23%) newly diagnosed dysglycaemia. Compared with the normoglycaemic participants, those with dysglycaemia had a higher proportion with first myocardial infarction (61% vs 45%, p < 0.0001) and were more often antiphospholipid antibody IgG positive (8% vs 5%; p = 0.013). HbA1c, fasting glucose and 2-h glucose were significantly associated to antiphospholipid antibody IgG. Odds ratios (ORs) were 1.04 (95% confidence interval [CI] 1.02–1.06), 1.14 (95% CI 1.00 – 1.27) and 1.12 (95% CI 1.04 – 1.21), respectively, after adjustments for age, gender and smoking. Conclusions: This study reports an association between antiphospholipid antibody IgG positivity and dysglycaemia. Further studies are needed to verify these findings and to investigate if antithrombotic therapy reduces vascular complications in antiphospholipid antibody positive subjects with dysglycaemia.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1335-P
Author(s):  
JOON YOUNG KIM ◽  
HALA TFAYLI ◽  
FIDA BACHA ◽  
SARA MICHALISZYN ◽  
SILVA A. ARSLANIAN

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